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RISS 인기검색어
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- 저자 : Ahmad Reza Mehdipour (검색결과 1 건)
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Reversal of multidrug resistance in cancer cells by novel asymmetrical 1,4-dihydropyridines
Omidreza Firuzi,Katayoun Javidnia,Elham Mansourabadi,Luciano Saso,Ahmad Reza Mehdipour,Ramin Miri 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.11
Multidrug resistance (MDR) is an importantobstacle that limits the efficacy of chemotherapy in manytypes of cancer. In this study, 14 novel asymmetrical DHPspossessing pyridyl alkyl carboxylate substitutions at C3 andalkyl carboxylate groups at C5 in addition to a nitroimidazoleor nitrophenyl moiety at C4 position were synthesized. Calciumchannel blocking (CCB) activity was measured inguinea pig ileal longitudinal smooth muscle. Cytotoxicitywas tested on 4 human cancer cell lines, while MDR reversalcapacity was examined on P-glycoprotein overexpressingdoxorubicin resistant MES-SA-DX5 and compared withnon-resistant MES-SA cells. Compounds showed differentCCB (IC50: 29.3 nM–4.75 lM) and cytotoxic activities(IC50: 6.4 to more than 100 lM). Several compounds havingnitrophenyl moiety at C4, could significantly reverse resistanceto doxorubicin at 0.5 and 1 lM. The most active oneswere 7e and 7g containing ethyl carboxylate and isopropylcarboxylate at C5, respectively. CCB activity, which isconsidered an undesirable effect for these agents, of 7e and7g were 33 and 20 times lower than nifedipine, respectively. In conclusion, the newly synthesized asymmetrical DHPcompounds showed promising MDR reversal and antitumoralactivities with low CCB effects and could be of therapeuticvalue in drug resistant cancer.
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