Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity

To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against five cancer cell lines. Especial...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Diao, Peng-Cheng [verfasserIn] Lin, Wei-Yuan [verfasserIn] Jian, Xie-Er [verfasserIn] Li, Yan-Hong [verfasserIn] You, Wen-Wei [verfasserIn] Zhao, Pei-Liang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Pyrimidine Benzothiazole Antiproliferative activity CDK2 inhibitor

Übergeordnetes Werk:	Enthalten in: European journal of medicinal chemistry - Amsterdam [u.a.] : Elsevier Science, 1987, 179, Seite 196-207
Übergeordnetes Werk:	volume:179 ; pages:196-207

DOI / URN:	10.1016/j.ejmech.2019.06.055

Katalog-ID:	ELV002794284

Internformat


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100	1		\|a Diao, Peng-Cheng \|e verfasserin \|4 aut
245	1	0	\|a Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity
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520			\|a To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against five cancer cell lines. Especially, the analogue 10s exhibited approximately potency with AZD5438 toward four cells including HeLa, HCT116, PC-3, and MDA-MB-231 with IC50 values of 0.45, 0.70, 0.92, 1.80 μM, respectively. More interestingly, the most highly active compound 10s in this study also possessed promising CDK2/cyclin A2 inhibitory activities with IC50 values of 15.4 nM, which was almost 3-fold potent than positive control AZD5438, and molecular docking studies revealed that the analogue bound efficiently with the CDK2 binding site. Further studies indicated that compound 10s could induce cell cycle arrest and apoptosis in a concentration-dependent manner. These observations suggest that pyrimidine-benzothiazole hybrids represent a new class of CDK2 inhibitors and well worth further investigation aiming to generate potential anticancer agents.
650		4	\|a Pyrimidine
650		4	\|a Benzothiazole
650		4	\|a Antiproliferative activity
650		4	\|a CDK2 inhibitor
700	1		\|a Lin, Wei-Yuan \|e verfasserin \|4 aut
700	1		\|a Jian, Xie-Er \|e verfasserin \|4 aut
700	1		\|a Li, Yan-Hong \|e verfasserin \|4 aut
700	1		\|a You, Wen-Wei \|e verfasserin \|4 aut
700	1		\|a Zhao, Pei-Liang \|e verfasserin \|4 aut
773	0	8	\|i Enthalten in \|t European journal of medicinal chemistry \|d Amsterdam [u.a.] : Elsevier Science, 1987 \|g 179, Seite 196-207 \|h Online-Ressource \|w (DE-627)320443213 \|w (DE-600)2005170-0 \|w (DE-576)25927125X \|x 1768-3254 \|7 nnns
773	1	8	\|g volume:179 \|g pages:196-207
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912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_65
912			\|a GBV_ILN_69
912			\|a GBV_ILN_70
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_90
912			\|a GBV_ILN_95
912			\|a GBV_ILN_100
912			\|a GBV_ILN_101
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_150
912			\|a GBV_ILN_151
912			\|a GBV_ILN_224
912			\|a GBV_ILN_370
912			\|a GBV_ILN_602
912			\|a GBV_ILN_702
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2004
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2015
912			\|a GBV_ILN_2020
912			\|a GBV_ILN_2021
912			\|a GBV_ILN_2025
912			\|a GBV_ILN_2027
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2038
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2049
912			\|a GBV_ILN_2050
912			\|a GBV_ILN_2056
912			\|a GBV_ILN_2059
912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2064
912			\|a GBV_ILN_2065
912			\|a GBV_ILN_2068
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_2112
912			\|a GBV_ILN_2113
912			\|a GBV_ILN_2118
912			\|a GBV_ILN_2122
912			\|a GBV_ILN_2129
912			\|a GBV_ILN_2143
912			\|a GBV_ILN_2147
912			\|a GBV_ILN_2148
912			\|a GBV_ILN_2152
912			\|a GBV_ILN_2153
912			\|a GBV_ILN_2190
912			\|a GBV_ILN_2336
912			\|a GBV_ILN_2507
912			\|a GBV_ILN_2522
912			\|a GBV_ILN_4035
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
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912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4242
912			\|a GBV_ILN_4251
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4333
912			\|a GBV_ILN_4334
912			\|a GBV_ILN_4335
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4393
936	b	k	\|a 44.42 \|j Pharmazeutische Chemie
951			\|a AR
952			\|d 179 \|h 196-207

Indexfelder

author_variant	p c d pcd w y l wyl x e j xej y h l yhl w w y wwy p l z plz
matchkey_str	article:17683254:2019----::icvronvlyiiieaebnohaoeeiaieaptnccidpnetiaei
hierarchy_sort_str	2019
bklnumber	44.42
publishDate	2019
allfields	10.1016/j.ejmech.2019.06.055 doi (DE-627)ELV002794284 (ELSEVIER)S0223-5234(19)30582-3 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.42 bkl Diao, Peng-Cheng verfasserin aut Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against five cancer cell lines. Especially, the analogue 10s exhibited approximately potency with AZD5438 toward four cells including HeLa, HCT116, PC-3, and MDA-MB-231 with IC50 values of 0.45, 0.70, 0.92, 1.80 μM, respectively. More interestingly, the most highly active compound 10s in this study also possessed promising CDK2/cyclin A2 inhibitory activities with IC50 values of 15.4 nM, which was almost 3-fold potent than positive control AZD5438, and molecular docking studies revealed that the analogue bound efficiently with the CDK2 binding site. Further studies indicated that compound 10s could induce cell cycle arrest and apoptosis in a concentration-dependent manner. These observations suggest that pyrimidine-benzothiazole hybrids represent a new class of CDK2 inhibitors and well worth further investigation aiming to generate potential anticancer agents. Pyrimidine Benzothiazole Antiproliferative activity CDK2 inhibitor Lin, Wei-Yuan verfasserin aut Jian, Xie-Er verfasserin aut Li, Yan-Hong verfasserin aut You, Wen-Wei verfasserin aut Zhao, Pei-Liang verfasserin aut Enthalten in European journal of medicinal chemistry Amsterdam [u.a.] : Elsevier Science, 1987 179, Seite 196-207 Online-Ressource (DE-627)320443213 (DE-600)2005170-0 (DE-576)25927125X 1768-3254 nnns volume:179 pages:196-207 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.42 Pharmazeutische Chemie AR 179 196-207
spelling	10.1016/j.ejmech.2019.06.055 doi (DE-627)ELV002794284 (ELSEVIER)S0223-5234(19)30582-3 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.42 bkl Diao, Peng-Cheng verfasserin aut Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against five cancer cell lines. Especially, the analogue 10s exhibited approximately potency with AZD5438 toward four cells including HeLa, HCT116, PC-3, and MDA-MB-231 with IC50 values of 0.45, 0.70, 0.92, 1.80 μM, respectively. More interestingly, the most highly active compound 10s in this study also possessed promising CDK2/cyclin A2 inhibitory activities with IC50 values of 15.4 nM, which was almost 3-fold potent than positive control AZD5438, and molecular docking studies revealed that the analogue bound efficiently with the CDK2 binding site. Further studies indicated that compound 10s could induce cell cycle arrest and apoptosis in a concentration-dependent manner. These observations suggest that pyrimidine-benzothiazole hybrids represent a new class of CDK2 inhibitors and well worth further investigation aiming to generate potential anticancer agents. Pyrimidine Benzothiazole Antiproliferative activity CDK2 inhibitor Lin, Wei-Yuan verfasserin aut Jian, Xie-Er verfasserin aut Li, Yan-Hong verfasserin aut You, Wen-Wei verfasserin aut Zhao, Pei-Liang verfasserin aut Enthalten in European journal of medicinal chemistry Amsterdam [u.a.] : Elsevier Science, 1987 179, Seite 196-207 Online-Ressource (DE-627)320443213 (DE-600)2005170-0 (DE-576)25927125X 1768-3254 nnns volume:179 pages:196-207 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.42 Pharmazeutische Chemie AR 179 196-207
allfields_unstemmed	10.1016/j.ejmech.2019.06.055 doi (DE-627)ELV002794284 (ELSEVIER)S0223-5234(19)30582-3 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.42 bkl Diao, Peng-Cheng verfasserin aut Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against five cancer cell lines. Especially, the analogue 10s exhibited approximately potency with AZD5438 toward four cells including HeLa, HCT116, PC-3, and MDA-MB-231 with IC50 values of 0.45, 0.70, 0.92, 1.80 μM, respectively. More interestingly, the most highly active compound 10s in this study also possessed promising CDK2/cyclin A2 inhibitory activities with IC50 values of 15.4 nM, which was almost 3-fold potent than positive control AZD5438, and molecular docking studies revealed that the analogue bound efficiently with the CDK2 binding site. Further studies indicated that compound 10s could induce cell cycle arrest and apoptosis in a concentration-dependent manner. These observations suggest that pyrimidine-benzothiazole hybrids represent a new class of CDK2 inhibitors and well worth further investigation aiming to generate potential anticancer agents. Pyrimidine Benzothiazole Antiproliferative activity CDK2 inhibitor Lin, Wei-Yuan verfasserin aut Jian, Xie-Er verfasserin aut Li, Yan-Hong verfasserin aut You, Wen-Wei verfasserin aut Zhao, Pei-Liang verfasserin aut Enthalten in European journal of medicinal chemistry Amsterdam [u.a.] : Elsevier Science, 1987 179, Seite 196-207 Online-Ressource (DE-627)320443213 (DE-600)2005170-0 (DE-576)25927125X 1768-3254 nnns volume:179 pages:196-207 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.42 Pharmazeutische Chemie AR 179 196-207
allfieldsGer	10.1016/j.ejmech.2019.06.055 doi (DE-627)ELV002794284 (ELSEVIER)S0223-5234(19)30582-3 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.42 bkl Diao, Peng-Cheng verfasserin aut Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against five cancer cell lines. Especially, the analogue 10s exhibited approximately potency with AZD5438 toward four cells including HeLa, HCT116, PC-3, and MDA-MB-231 with IC50 values of 0.45, 0.70, 0.92, 1.80 μM, respectively. More interestingly, the most highly active compound 10s in this study also possessed promising CDK2/cyclin A2 inhibitory activities with IC50 values of 15.4 nM, which was almost 3-fold potent than positive control AZD5438, and molecular docking studies revealed that the analogue bound efficiently with the CDK2 binding site. Further studies indicated that compound 10s could induce cell cycle arrest and apoptosis in a concentration-dependent manner. These observations suggest that pyrimidine-benzothiazole hybrids represent a new class of CDK2 inhibitors and well worth further investigation aiming to generate potential anticancer agents. Pyrimidine Benzothiazole Antiproliferative activity CDK2 inhibitor Lin, Wei-Yuan verfasserin aut Jian, Xie-Er verfasserin aut Li, Yan-Hong verfasserin aut You, Wen-Wei verfasserin aut Zhao, Pei-Liang verfasserin aut Enthalten in European journal of medicinal chemistry Amsterdam [u.a.] : Elsevier Science, 1987 179, Seite 196-207 Online-Ressource (DE-627)320443213 (DE-600)2005170-0 (DE-576)25927125X 1768-3254 nnns volume:179 pages:196-207 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.42 Pharmazeutische Chemie AR 179 196-207
allfieldsSound	10.1016/j.ejmech.2019.06.055 doi (DE-627)ELV002794284 (ELSEVIER)S0223-5234(19)30582-3 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.42 bkl Diao, Peng-Cheng verfasserin aut Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against five cancer cell lines. Especially, the analogue 10s exhibited approximately potency with AZD5438 toward four cells including HeLa, HCT116, PC-3, and MDA-MB-231 with IC50 values of 0.45, 0.70, 0.92, 1.80 μM, respectively. More interestingly, the most highly active compound 10s in this study also possessed promising CDK2/cyclin A2 inhibitory activities with IC50 values of 15.4 nM, which was almost 3-fold potent than positive control AZD5438, and molecular docking studies revealed that the analogue bound efficiently with the CDK2 binding site. Further studies indicated that compound 10s could induce cell cycle arrest and apoptosis in a concentration-dependent manner. These observations suggest that pyrimidine-benzothiazole hybrids represent a new class of CDK2 inhibitors and well worth further investigation aiming to generate potential anticancer agents. Pyrimidine Benzothiazole Antiproliferative activity CDK2 inhibitor Lin, Wei-Yuan verfasserin aut Jian, Xie-Er verfasserin aut Li, Yan-Hong verfasserin aut You, Wen-Wei verfasserin aut Zhao, Pei-Liang verfasserin aut Enthalten in European journal of medicinal chemistry Amsterdam [u.a.] : Elsevier Science, 1987 179, Seite 196-207 Online-Ressource (DE-627)320443213 (DE-600)2005170-0 (DE-576)25927125X 1768-3254 nnns volume:179 pages:196-207 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.42 Pharmazeutische Chemie AR 179 196-207
language	English
source	Enthalten in European journal of medicinal chemistry 179, Seite 196-207 volume:179 pages:196-207
sourceStr	Enthalten in European journal of medicinal chemistry 179, Seite 196-207 volume:179 pages:196-207
format_phy_str_mv	Article
bklname	Pharmazeutische Chemie
institution	findex.gbv.de
topic_facet	Pyrimidine Benzothiazole Antiproliferative activity CDK2 inhibitor
dewey-raw	610
isfreeaccess_bool	false
container_title	European journal of medicinal chemistry
authorswithroles_txt_mv	Diao, Peng-Cheng @@aut@@ Lin, Wei-Yuan @@aut@@ Jian, Xie-Er @@aut@@ Li, Yan-Hong @@aut@@ You, Wen-Wei @@aut@@ Zhao, Pei-Liang @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	320443213
dewey-sort	3610
id	ELV002794284
language_de	englisch
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author	Diao, Peng-Cheng
spellingShingle	Diao, Peng-Cheng ddc 610 ssgn 15,3 fid PHARM bkl 44.42 misc Pyrimidine misc Benzothiazole misc Antiproliferative activity misc CDK2 inhibitor Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity
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topic_title	610 DE-600 15,3 ssgn PHARM DE-84 fid 44.42 bkl Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity Pyrimidine Benzothiazole Antiproliferative activity CDK2 inhibitor
topic	ddc 610 ssgn 15,3 fid PHARM bkl 44.42 misc Pyrimidine misc Benzothiazole misc Antiproliferative activity misc CDK2 inhibitor
topic_unstemmed	ddc 610 ssgn 15,3 fid PHARM bkl 44.42 misc Pyrimidine misc Benzothiazole misc Antiproliferative activity misc CDK2 inhibitor
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title	Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity
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title_full	Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity
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author_browse	Diao, Peng-Cheng Lin, Wei-Yuan Jian, Xie-Er Li, Yan-Hong You, Wen-Wei Zhao, Pei-Liang
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doi_str_mv	10.1016/j.ejmech.2019.06.055
dewey-full	610
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title_sort	discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity
title_auth	Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity
abstract	To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against five cancer cell lines. Especially, the analogue 10s exhibited approximately potency with AZD5438 toward four cells including HeLa, HCT116, PC-3, and MDA-MB-231 with IC50 values of 0.45, 0.70, 0.92, 1.80 μM, respectively. More interestingly, the most highly active compound 10s in this study also possessed promising CDK2/cyclin A2 inhibitory activities with IC50 values of 15.4 nM, which was almost 3-fold potent than positive control AZD5438, and molecular docking studies revealed that the analogue bound efficiently with the CDK2 binding site. Further studies indicated that compound 10s could induce cell cycle arrest and apoptosis in a concentration-dependent manner. These observations suggest that pyrimidine-benzothiazole hybrids represent a new class of CDK2 inhibitors and well worth further investigation aiming to generate potential anticancer agents.
abstractGer	To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against five cancer cell lines. Especially, the analogue 10s exhibited approximately potency with AZD5438 toward four cells including HeLa, HCT116, PC-3, and MDA-MB-231 with IC50 values of 0.45, 0.70, 0.92, 1.80 μM, respectively. More interestingly, the most highly active compound 10s in this study also possessed promising CDK2/cyclin A2 inhibitory activities with IC50 values of 15.4 nM, which was almost 3-fold potent than positive control AZD5438, and molecular docking studies revealed that the analogue bound efficiently with the CDK2 binding site. Further studies indicated that compound 10s could induce cell cycle arrest and apoptosis in a concentration-dependent manner. These observations suggest that pyrimidine-benzothiazole hybrids represent a new class of CDK2 inhibitors and well worth further investigation aiming to generate potential anticancer agents.
abstract_unstemmed	To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against five cancer cell lines. Especially, the analogue 10s exhibited approximately potency with AZD5438 toward four cells including HeLa, HCT116, PC-3, and MDA-MB-231 with IC50 values of 0.45, 0.70, 0.92, 1.80 μM, respectively. More interestingly, the most highly active compound 10s in this study also possessed promising CDK2/cyclin A2 inhibitory activities with IC50 values of 15.4 nM, which was almost 3-fold potent than positive control AZD5438, and molecular docking studies revealed that the analogue bound efficiently with the CDK2 binding site. Further studies indicated that compound 10s could induce cell cycle arrest and apoptosis in a concentration-dependent manner. These observations suggest that pyrimidine-benzothiazole hybrids represent a new class of CDK2 inhibitors and well worth further investigation aiming to generate potential anticancer agents.
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title_short	Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity
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author2	Lin, Wei-Yuan Jian, Xie-Er Li, Yan-Hong You, Wen-Wei Zhao, Pei-Liang
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up_date	2024-07-06T17:28:29.367Z
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Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity

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