Shah A, Gaveriya H, Motohashi N, Kawase M, Saito S, Sakagami H, Satoh K, Tada Y, Solymosi A, Walfard K, Molnar J
Department of Chemistry, Saurashtra University, Rajkot, India.
Anticancer Res. 2000 Jan-Feb;20(1A):373-7.
Eleven 4-phenyl-3,5-diacetyl-1,4-dihydropyridines (AcDHPs) [G1-11] substituted at the phenyl ring were synthesized and compared for their cytotoxic activity and multidrug resistance (MDR)-reversing activity in in vitro assay systems. Among them, compound [G7] showed the highest cytotoxic activity against human promyelocytic leukemia HL-60 and human squamous cell carcinoma HSC-2 cells. However, no compounds tested produced radicals at pH 7.4-12.5. The activity of P-glycoprotein (Pgp) responsible for MDR in tumor cells was reduced by compounds [G2, 3, 6, 5, 8, 1, 11], verapamil [VP] and nifedipine [NP]. However, compounds [G4, 7, 10] were hardly active while G9 did not show a MDR reversing effect at 2.0-20.0 micrograms/mL. These data show a relationship between chemical structures and MDR-reversing effect on tumor cells.
合成了11种在苯环上有取代基的4-苯基-3,5-二乙酰基-1,4-二氢吡啶（AcDHPs）[G1 - 11]，并在体外分析系统中比较了它们的细胞毒性活性和多药耐药性（MDR）逆转活性。其中，化合物[G7]对人早幼粒细胞白血病HL - 60和人鳞状细胞癌HSC - 2细胞显示出最高的细胞毒性活性。然而，在pH 7.4 - 12.5条件下，所测试的化合物均未产生自由基。负责肿瘤细胞中MDR的P - 糖蛋白（Pgp）的活性被化合物[G2、3、6、5、8、1、11]、维拉帕米[VP]和硝苯地平[NP]降低。然而，化合物[G4、7、10]几乎没有活性，而G9在2.0 - 20.0微克/毫升时未显示出MDR逆转作用。这些数据表明了化学结构与对肿瘤细胞的MDR逆转作用之间的关系。
