Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents
The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Jovanović Milan [verfasserIn] Nikolić Katarina [verfasserIn] Gagić Žarko [verfasserIn] Agbaba Danica [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
srp |
| Erschienen: |
2018 |
|---|
| Schlagwörter: |
|---|
| Übergeordnetes Werk: |
In: Arhiv za farmaciju - Pharmaceutical Association of Serbia, Belgrade, Serbia, 2018, 68(2018), 4, Seite 860-873 |
|---|---|
| Übergeordnetes Werk: |
volume:68 ; year:2018 ; number:4 ; pages:860-873 |
| Links: |
Link aufrufen |
|---|
| DOI / URN: |
10.5937/ArhFarm1804860J |
|---|
| Katalog-ID: |
DOAJ04867365X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ04867365X | ||
| 003 | DE-627 | ||
| 005 | 20230501211910.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230227s2018 xx |||||o 00| ||srp c | ||
| 024 | 7 | |a 10.5937/ArhFarm1804860J |2 doi | |
| 035 | |a (DE-627)DOAJ04867365X | ||
| 035 | |a (DE-599)DOAJa3ac120c092541459cb74de0759fd753 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a srp | ||
| 050 | 0 | |a RS1-441 | |
| 100 | 0 | |a Jovanović Milan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs. | ||
| 650 | 4 | |a 3d-qsar | |
| 650 | 4 | |a pharmacophore | |
| 650 | 4 | |a pi3k-α | |
| 650 | 4 | |a inhibitor | |
| 650 | 4 | |a tumor | |
| 653 | 0 | |a Pharmacy and materia medica | |
| 700 | 0 | |a Nikolić Katarina |e verfasserin |4 aut | |
| 700 | 0 | |a Gagić Žarko |e verfasserin |4 aut | |
| 700 | 0 | |a Agbaba Danica |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t Arhiv za farmaciju |d Pharmaceutical Association of Serbia, Belgrade, Serbia, 2018 |g 68(2018), 4, Seite 860-873 |w (DE-627)1692190660 |x 22178767 |7 nnns |
| 773 | 1 | 8 | |g volume:68 |g year:2018 |g number:4 |g pages:860-873 |
| 856 | 4 | 0 | |u https://doi.org/10.5937/ArhFarm1804860J |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/a3ac120c092541459cb74de0759fd753 |z kostenfrei |
| 856 | 4 | 0 | |u https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2018/0004-19631804860J.pdf |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/0004-1963 |y Journal toc |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/2217-8767 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |d 68 |j 2018 |e 4 |h 860-873 | ||
| author_variant |
j m jm n k nk g ž gž a d ad |
|---|---|
| matchkey_str |
article:22178767:2018----::oeuamdlnadnlssfh3pamcpoetutroteeetvp3 |
| hierarchy_sort_str |
2018 |
| callnumber-subject-code |
RS |
| publishDate |
2018 |
| allfields |
10.5937/ArhFarm1804860J doi (DE-627)DOAJ04867365X (DE-599)DOAJa3ac120c092541459cb74de0759fd753 DE-627 ger DE-627 rakwb srp RS1-441 Jovanović Milan verfasserin aut Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs. 3d-qsar pharmacophore pi3k-α inhibitor tumor Pharmacy and materia medica Nikolić Katarina verfasserin aut Gagić Žarko verfasserin aut Agbaba Danica verfasserin aut In Arhiv za farmaciju Pharmaceutical Association of Serbia, Belgrade, Serbia, 2018 68(2018), 4, Seite 860-873 (DE-627)1692190660 22178767 nnns volume:68 year:2018 number:4 pages:860-873 https://doi.org/10.5937/ArhFarm1804860J kostenfrei https://doaj.org/article/a3ac120c092541459cb74de0759fd753 kostenfrei https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2018/0004-19631804860J.pdf kostenfrei https://doaj.org/toc/0004-1963 Journal toc kostenfrei https://doaj.org/toc/2217-8767 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA AR 68 2018 4 860-873 |
| spelling |
10.5937/ArhFarm1804860J doi (DE-627)DOAJ04867365X (DE-599)DOAJa3ac120c092541459cb74de0759fd753 DE-627 ger DE-627 rakwb srp RS1-441 Jovanović Milan verfasserin aut Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs. 3d-qsar pharmacophore pi3k-α inhibitor tumor Pharmacy and materia medica Nikolić Katarina verfasserin aut Gagić Žarko verfasserin aut Agbaba Danica verfasserin aut In Arhiv za farmaciju Pharmaceutical Association of Serbia, Belgrade, Serbia, 2018 68(2018), 4, Seite 860-873 (DE-627)1692190660 22178767 nnns volume:68 year:2018 number:4 pages:860-873 https://doi.org/10.5937/ArhFarm1804860J kostenfrei https://doaj.org/article/a3ac120c092541459cb74de0759fd753 kostenfrei https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2018/0004-19631804860J.pdf kostenfrei https://doaj.org/toc/0004-1963 Journal toc kostenfrei https://doaj.org/toc/2217-8767 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA AR 68 2018 4 860-873 |
| allfields_unstemmed |
10.5937/ArhFarm1804860J doi (DE-627)DOAJ04867365X (DE-599)DOAJa3ac120c092541459cb74de0759fd753 DE-627 ger DE-627 rakwb srp RS1-441 Jovanović Milan verfasserin aut Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs. 3d-qsar pharmacophore pi3k-α inhibitor tumor Pharmacy and materia medica Nikolić Katarina verfasserin aut Gagić Žarko verfasserin aut Agbaba Danica verfasserin aut In Arhiv za farmaciju Pharmaceutical Association of Serbia, Belgrade, Serbia, 2018 68(2018), 4, Seite 860-873 (DE-627)1692190660 22178767 nnns volume:68 year:2018 number:4 pages:860-873 https://doi.org/10.5937/ArhFarm1804860J kostenfrei https://doaj.org/article/a3ac120c092541459cb74de0759fd753 kostenfrei https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2018/0004-19631804860J.pdf kostenfrei https://doaj.org/toc/0004-1963 Journal toc kostenfrei https://doaj.org/toc/2217-8767 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA AR 68 2018 4 860-873 |
| allfieldsGer |
10.5937/ArhFarm1804860J doi (DE-627)DOAJ04867365X (DE-599)DOAJa3ac120c092541459cb74de0759fd753 DE-627 ger DE-627 rakwb srp RS1-441 Jovanović Milan verfasserin aut Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs. 3d-qsar pharmacophore pi3k-α inhibitor tumor Pharmacy and materia medica Nikolić Katarina verfasserin aut Gagić Žarko verfasserin aut Agbaba Danica verfasserin aut In Arhiv za farmaciju Pharmaceutical Association of Serbia, Belgrade, Serbia, 2018 68(2018), 4, Seite 860-873 (DE-627)1692190660 22178767 nnns volume:68 year:2018 number:4 pages:860-873 https://doi.org/10.5937/ArhFarm1804860J kostenfrei https://doaj.org/article/a3ac120c092541459cb74de0759fd753 kostenfrei https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2018/0004-19631804860J.pdf kostenfrei https://doaj.org/toc/0004-1963 Journal toc kostenfrei https://doaj.org/toc/2217-8767 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA AR 68 2018 4 860-873 |
| allfieldsSound |
10.5937/ArhFarm1804860J doi (DE-627)DOAJ04867365X (DE-599)DOAJa3ac120c092541459cb74de0759fd753 DE-627 ger DE-627 rakwb srp RS1-441 Jovanović Milan verfasserin aut Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs. 3d-qsar pharmacophore pi3k-α inhibitor tumor Pharmacy and materia medica Nikolić Katarina verfasserin aut Gagić Žarko verfasserin aut Agbaba Danica verfasserin aut In Arhiv za farmaciju Pharmaceutical Association of Serbia, Belgrade, Serbia, 2018 68(2018), 4, Seite 860-873 (DE-627)1692190660 22178767 nnns volume:68 year:2018 number:4 pages:860-873 https://doi.org/10.5937/ArhFarm1804860J kostenfrei https://doaj.org/article/a3ac120c092541459cb74de0759fd753 kostenfrei https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2018/0004-19631804860J.pdf kostenfrei https://doaj.org/toc/0004-1963 Journal toc kostenfrei https://doaj.org/toc/2217-8767 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA AR 68 2018 4 860-873 |
| source |
In Arhiv za farmaciju 68(2018), 4, Seite 860-873 volume:68 year:2018 number:4 pages:860-873 |
| sourceStr |
In Arhiv za farmaciju 68(2018), 4, Seite 860-873 volume:68 year:2018 number:4 pages:860-873 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
3d-qsar pharmacophore pi3k-α inhibitor tumor Pharmacy and materia medica |
| isfreeaccess_bool |
true |
| container_title |
Arhiv za farmaciju |
| authorswithroles_txt_mv |
Jovanović Milan @@aut@@ Nikolić Katarina @@aut@@ Gagić Žarko @@aut@@ Agbaba Danica @@aut@@ |
| publishDateDaySort_date |
2018-01-01T00:00:00Z |
| hierarchy_top_id |
1692190660 |
| id |
DOAJ04867365X |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ04867365X</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230501211910.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230227s2018 xx |||||o 00| ||srp c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.5937/ArhFarm1804860J</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ04867365X</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJa3ac120c092541459cb74de0759fd753</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">srp</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RS1-441</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Jovanović Milan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">3d-qsar</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">pharmacophore</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">pi3k-α</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">inhibitor</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">tumor</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Pharmacy and materia medica</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nikolić Katarina</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Gagić Žarko</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Agbaba Danica</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Arhiv za farmaciju</subfield><subfield code="d">Pharmaceutical Association of Serbia, Belgrade, Serbia, 2018</subfield><subfield code="g">68(2018), 4, Seite 860-873</subfield><subfield code="w">(DE-627)1692190660</subfield><subfield code="x">22178767</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:68</subfield><subfield code="g">year:2018</subfield><subfield code="g">number:4</subfield><subfield code="g">pages:860-873</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.5937/ArhFarm1804860J</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/a3ac120c092541459cb74de0759fd753</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2018/0004-19631804860J.pdf</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/0004-1963</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2217-8767</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">68</subfield><subfield code="j">2018</subfield><subfield code="e">4</subfield><subfield code="h">860-873</subfield></datafield></record></collection>
|
| callnumber-first |
R - Medicine |
| author |
Jovanović Milan |
| spellingShingle |
Jovanović Milan misc RS1-441 misc 3d-qsar misc pharmacophore misc pi3k-α misc inhibitor misc tumor misc Pharmacy and materia medica Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents |
| authorStr |
Jovanović Milan |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)1692190660 |
| format |
electronic Article |
| delete_txt_mv |
keep |
| author_role |
aut aut aut aut |
| collection |
DOAJ |
| remote_str |
true |
| callnumber-label |
RS1-441 |
| illustrated |
Not Illustrated |
| issn |
22178767 |
| topic_title |
RS1-441 Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents 3d-qsar pharmacophore pi3k-α inhibitor tumor |
| topic |
misc RS1-441 misc 3d-qsar misc pharmacophore misc pi3k-α misc inhibitor misc tumor misc Pharmacy and materia medica |
| topic_unstemmed |
misc RS1-441 misc 3d-qsar misc pharmacophore misc pi3k-α misc inhibitor misc tumor misc Pharmacy and materia medica |
| topic_browse |
misc RS1-441 misc 3d-qsar misc pharmacophore misc pi3k-α misc inhibitor misc tumor misc Pharmacy and materia medica |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
cr |
| hierarchy_parent_title |
Arhiv za farmaciju |
| hierarchy_parent_id |
1692190660 |
| hierarchy_top_title |
Arhiv za farmaciju |
| isfreeaccess_txt |
true |
| familylinks_str_mv |
(DE-627)1692190660 |
| title |
Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents |
| ctrlnum |
(DE-627)DOAJ04867365X (DE-599)DOAJa3ac120c092541459cb74de0759fd753 |
| title_full |
Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents |
| author_sort |
Jovanović Milan |
| journal |
Arhiv za farmaciju |
| journalStr |
Arhiv za farmaciju |
| callnumber-first-code |
R |
| lang_code |
srp |
| isOA_bool |
true |
| recordtype |
marc |
| publishDateSort |
2018 |
| contenttype_str_mv |
txt |
| container_start_page |
860 |
| author_browse |
Jovanović Milan Nikolić Katarina Gagić Žarko Agbaba Danica |
| container_volume |
68 |
| class |
RS1-441 |
| format_se |
Elektronische Aufsätze |
| author-letter |
Jovanović Milan |
| doi_str_mv |
10.5937/ArhFarm1804860J |
| author2-role |
verfasserin |
| title_sort |
molecular modeling and analysis of the 3d pharmacophore structure of the selective pi3k-α inhibitors as antitumor agents |
| callnumber |
RS1-441 |
| title_auth |
Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents |
| abstract |
The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs. |
| abstractGer |
The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs. |
| abstract_unstemmed |
The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs. |
| collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA |
| container_issue |
4 |
| title_short |
Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents |
| url |
https://doi.org/10.5937/ArhFarm1804860J https://doaj.org/article/a3ac120c092541459cb74de0759fd753 https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2018/0004-19631804860J.pdf https://doaj.org/toc/0004-1963 https://doaj.org/toc/2217-8767 |
| remote_bool |
true |
| author2 |
Nikolić Katarina Gagić Žarko Agbaba Danica |
| author2Str |
Nikolić Katarina Gagić Žarko Agbaba Danica |
| ppnlink |
1692190660 |
| callnumber-subject |
RS - Pharmacy |
| mediatype_str_mv |
c |
| isOA_txt |
true |
| hochschulschrift_bool |
false |
| doi_str |
10.5937/ArhFarm1804860J |
| callnumber-a |
RS1-441 |
| up_date |
2024-07-03T19:04:32.071Z |
| _version_ |
1803585818019758080 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ04867365X</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230501211910.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230227s2018 xx |||||o 00| ||srp c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.5937/ArhFarm1804860J</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ04867365X</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJa3ac120c092541459cb74de0759fd753</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">srp</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RS1-441</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Jovanović Milan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">3d-qsar</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">pharmacophore</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">pi3k-α</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">inhibitor</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">tumor</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Pharmacy and materia medica</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nikolić Katarina</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Gagić Žarko</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Agbaba Danica</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Arhiv za farmaciju</subfield><subfield code="d">Pharmaceutical Association of Serbia, Belgrade, Serbia, 2018</subfield><subfield code="g">68(2018), 4, Seite 860-873</subfield><subfield code="w">(DE-627)1692190660</subfield><subfield code="x">22178767</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:68</subfield><subfield code="g">year:2018</subfield><subfield code="g">number:4</subfield><subfield code="g">pages:860-873</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.5937/ArhFarm1804860J</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/a3ac120c092541459cb74de0759fd753</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2018/0004-19631804860J.pdf</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/0004-1963</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2217-8767</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">68</subfield><subfield code="j">2018</subfield><subfield code="e">4</subfield><subfield code="h">860-873</subfield></datafield></record></collection>
|
| score |
7.4018297 |