Pyrazolo[4,3-<ce:italic>b</ce:italic>]pyrimido[4,5-<ce:italic>e</ce:italic>][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR
Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Zhang, Qiumeng [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2018transfer abstract |
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| Schlagwörter: |
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| Umfang: |
14 |
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| Übergeordnetes Werk: |
Enthalten in: Electrochemical synthesis, photodegradation and antibacterial properties of PEG capped zinc oxide nanoparticles - Jose, Ajay ELSEVIER, 2018, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:158 ; year:2018 ; day:5 ; month:10 ; pages:428-441 ; extent:14 |
| Links: |
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| DOI / URN: |
10.1016/j.ejmech.2018.09.032 |
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ELV044341849 |
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| 245 | 1 | 0 | |a Pyrazolo[4,3-<ce:italic>b</ce:italic>]pyrimido[4,5-<ce:italic>e</ce:italic>][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR |
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| 520 | |a Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. | ||
| 520 | |a Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. | ||
| 650 | 7 | |a KDR |2 Elsevier | |
| 650 | 7 | |a Anticancer |2 Elsevier | |
| 650 | 7 | |a Aurora B |2 Elsevier | |
| 650 | 7 | |a Multi-targeted |2 Elsevier | |
| 650 | 7 | |a Heterocyclic |2 Elsevier | |
| 650 | 7 | |a Aurora A |2 Elsevier | |
| 700 | 1 | |a Shen, Qianqian |4 oth | |
| 700 | 1 | |a Gao, Lixin |4 oth | |
| 700 | 1 | |a Tong, Linjiang |4 oth | |
| 700 | 1 | |a Li, Jia |4 oth | |
| 700 | 1 | |a Chen, Yi |4 oth | |
| 700 | 1 | |a Lu, Wei |4 oth | |
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10.1016/j.ejmech.2018.09.032 doi GBV00000000000385.pica (DE-627)ELV044341849 (ELSEVIER)S0223-5234(18)30804-3 DE-627 ger DE-627 rakwb eng 570 540 VZ BIODIV DE-30 fid 42.00 bkl Zhang, Qiumeng verfasserin aut Pyrazolo[4,3-<ce:italic>b</ce:italic>]pyrimido[4,5-<ce:italic>e</ce:italic>][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR 2018transfer abstract 14 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. KDR Elsevier Anticancer Elsevier Aurora B Elsevier Multi-targeted Elsevier Heterocyclic Elsevier Aurora A Elsevier Shen, Qianqian oth Gao, Lixin oth Tong, Linjiang oth Li, Jia oth Chen, Yi oth Lu, Wei oth Enthalten in Elsevier Science Jose, Ajay ELSEVIER Electrochemical synthesis, photodegradation and antibacterial properties of PEG capped zinc oxide nanoparticles 2018 Amsterdam [u.a.] (DE-627)ELV000457477 volume:158 year:2018 day:5 month:10 pages:428-441 extent:14 https://doi.org/10.1016/j.ejmech.2018.09.032 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 42.00 Biologie: Allgemeines VZ AR 158 2018 5 1005 428-441 14 |
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10.1016/j.ejmech.2018.09.032 doi GBV00000000000385.pica (DE-627)ELV044341849 (ELSEVIER)S0223-5234(18)30804-3 DE-627 ger DE-627 rakwb eng 570 540 VZ BIODIV DE-30 fid 42.00 bkl Zhang, Qiumeng verfasserin aut Pyrazolo[4,3-<ce:italic>b</ce:italic>]pyrimido[4,5-<ce:italic>e</ce:italic>][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR 2018transfer abstract 14 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. KDR Elsevier Anticancer Elsevier Aurora B Elsevier Multi-targeted Elsevier Heterocyclic Elsevier Aurora A Elsevier Shen, Qianqian oth Gao, Lixin oth Tong, Linjiang oth Li, Jia oth Chen, Yi oth Lu, Wei oth Enthalten in Elsevier Science Jose, Ajay ELSEVIER Electrochemical synthesis, photodegradation and antibacterial properties of PEG capped zinc oxide nanoparticles 2018 Amsterdam [u.a.] (DE-627)ELV000457477 volume:158 year:2018 day:5 month:10 pages:428-441 extent:14 https://doi.org/10.1016/j.ejmech.2018.09.032 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 42.00 Biologie: Allgemeines VZ AR 158 2018 5 1005 428-441 14 |
| allfields_unstemmed |
10.1016/j.ejmech.2018.09.032 doi GBV00000000000385.pica (DE-627)ELV044341849 (ELSEVIER)S0223-5234(18)30804-3 DE-627 ger DE-627 rakwb eng 570 540 VZ BIODIV DE-30 fid 42.00 bkl Zhang, Qiumeng verfasserin aut Pyrazolo[4,3-<ce:italic>b</ce:italic>]pyrimido[4,5-<ce:italic>e</ce:italic>][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR 2018transfer abstract 14 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. KDR Elsevier Anticancer Elsevier Aurora B Elsevier Multi-targeted Elsevier Heterocyclic Elsevier Aurora A Elsevier Shen, Qianqian oth Gao, Lixin oth Tong, Linjiang oth Li, Jia oth Chen, Yi oth Lu, Wei oth Enthalten in Elsevier Science Jose, Ajay ELSEVIER Electrochemical synthesis, photodegradation and antibacterial properties of PEG capped zinc oxide nanoparticles 2018 Amsterdam [u.a.] (DE-627)ELV000457477 volume:158 year:2018 day:5 month:10 pages:428-441 extent:14 https://doi.org/10.1016/j.ejmech.2018.09.032 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 42.00 Biologie: Allgemeines VZ AR 158 2018 5 1005 428-441 14 |
| allfieldsGer |
10.1016/j.ejmech.2018.09.032 doi GBV00000000000385.pica (DE-627)ELV044341849 (ELSEVIER)S0223-5234(18)30804-3 DE-627 ger DE-627 rakwb eng 570 540 VZ BIODIV DE-30 fid 42.00 bkl Zhang, Qiumeng verfasserin aut Pyrazolo[4,3-<ce:italic>b</ce:italic>]pyrimido[4,5-<ce:italic>e</ce:italic>][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR 2018transfer abstract 14 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. KDR Elsevier Anticancer Elsevier Aurora B Elsevier Multi-targeted Elsevier Heterocyclic Elsevier Aurora A Elsevier Shen, Qianqian oth Gao, Lixin oth Tong, Linjiang oth Li, Jia oth Chen, Yi oth Lu, Wei oth Enthalten in Elsevier Science Jose, Ajay ELSEVIER Electrochemical synthesis, photodegradation and antibacterial properties of PEG capped zinc oxide nanoparticles 2018 Amsterdam [u.a.] (DE-627)ELV000457477 volume:158 year:2018 day:5 month:10 pages:428-441 extent:14 https://doi.org/10.1016/j.ejmech.2018.09.032 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 42.00 Biologie: Allgemeines VZ AR 158 2018 5 1005 428-441 14 |
| allfieldsSound |
10.1016/j.ejmech.2018.09.032 doi GBV00000000000385.pica (DE-627)ELV044341849 (ELSEVIER)S0223-5234(18)30804-3 DE-627 ger DE-627 rakwb eng 570 540 VZ BIODIV DE-30 fid 42.00 bkl Zhang, Qiumeng verfasserin aut Pyrazolo[4,3-<ce:italic>b</ce:italic>]pyrimido[4,5-<ce:italic>e</ce:italic>][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR 2018transfer abstract 14 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. KDR Elsevier Anticancer Elsevier Aurora B Elsevier Multi-targeted Elsevier Heterocyclic Elsevier Aurora A Elsevier Shen, Qianqian oth Gao, Lixin oth Tong, Linjiang oth Li, Jia oth Chen, Yi oth Lu, Wei oth Enthalten in Elsevier Science Jose, Ajay ELSEVIER Electrochemical synthesis, photodegradation and antibacterial properties of PEG capped zinc oxide nanoparticles 2018 Amsterdam [u.a.] (DE-627)ELV000457477 volume:158 year:2018 day:5 month:10 pages:428-441 extent:14 https://doi.org/10.1016/j.ejmech.2018.09.032 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 42.00 Biologie: Allgemeines VZ AR 158 2018 5 1005 428-441 14 |
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Pyrazolo[4,3-<ce:italic>b</ce:italic>]pyrimido[4,5-<ce:italic>e</ce:italic>][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR |
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Pyrazolo[4,3-<ce:italic>b</ce:italic>]pyrimido[4,5-<ce:italic>e</ce:italic>][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR |
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pyrazolo[4,3-<ce:italic>b</ce:italic>]pyrimido[4,5-<ce:italic>e</ce:italic>][1,4]diazepine derivatives as new multi-targeted inhibitors of aurora a/b and kdr |
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Pyrazolo[4,3-<ce:italic>b</ce:italic>]pyrimido[4,5-<ce:italic>e</ce:italic>][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR |
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Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. |
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Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. |
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Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. |
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Pyrazolo[4,3-<ce:italic>b</ce:italic>]pyrimido[4,5-<ce:italic>e</ce:italic>][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR |
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All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound.</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">KDR</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Anticancer</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Aurora B</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Multi-targeted</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Heterocyclic</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Aurora A</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Shen, Qianqian</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gao, Lixin</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tong, Linjiang</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Li, Jia</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chen, Yi</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lu, Wei</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier Science</subfield><subfield code="a">Jose, Ajay ELSEVIER</subfield><subfield code="t">Electrochemical synthesis, photodegradation and antibacterial properties of PEG capped zinc oxide nanoparticles</subfield><subfield code="d">2018</subfield><subfield code="g">Amsterdam [u.a.]</subfield><subfield code="w">(DE-627)ELV000457477</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:158</subfield><subfield code="g">year:2018</subfield><subfield code="g">day:5</subfield><subfield code="g">month:10</subfield><subfield code="g">pages:428-441</subfield><subfield code="g">extent:14</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.ejmech.2018.09.032</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-BIODIV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">42.00</subfield><subfield code="j">Biologie: Allgemeines</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">158</subfield><subfield code="j">2018</subfield><subfield code="b">5</subfield><subfield code="c">1005</subfield><subfield code="h">428-441</subfield><subfield code="g">14</subfield></datafield></record></collection>
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