3,5-dibenzoyl-1,4-dihydropyridines:: Synthesis and MDR reversal in tumor cells

被引：212

作者：

Kawase, M ^{[1
]}

Shah, A

Gaveriya, H

Motohashi, N

Sakagami, H

Varga, A

Molnár, J

机构：

[1] Josai Univ, Fac Pharmaceut Sci, Sakado, Saitama 3500295, Japan

[2] Saurashtra Univ, Dept Chem, Rajkot 360005, Gujarat, India

[3] Meiji Pharmaceut Univ, Tokyo 2048588, Japan

[4] Meikai Univ, Sch Dent, Dept Dent Pharmacol, Sakado, Saitama 3500283, Japan

[5] Humboldt Univ, Dept Mol Parasitol, Berlin, Germany

[6] Albert Szent Gyorgyi Med Univ, Fac Med, Inst Microbiol, H-6701 Szeged, Hungary

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2002年 / 10卷 / 04期

关键词：

D O I：

10.1016/S0968-0896(01)00363-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fifteen 4-phenyl-3.5-dibenzoyl-1,4-dihydropyridines (BzDHPs) (1-15) substituted at the 4-phenyl ring were synthesized and compared to their cytotoxic activity and multidrug resistance (MDR)-reversing activity in in vitro assay systems. Among them, 2-CF3 (5) (IC50 =8.7 muM), 2-Cl (11) (IC50 = 7.0 muM) and 3-Cl (12) (IC50 = 7.0 muM) derivatives showed the highest cytotoxic activity against human oral squamous carcinoma (HSC-2) cells. The activity of P-glycoprotein (Pgp) responce for MDR in tumor cells was reduced by some of derivatives (3, 4, 8, 12), verapamil (VP) and nifedipine (NP). These data suggest that 3,5-dibenzoyl-4-(3-chlorophenyl)-1,4-dihydro-2,6-dimethylpyridine (12) can be recommended as a new drug candidate for MDR cancer treatment. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：1051 / 1055

页数：5

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