Dihydropyridines and atypical MDR: a novel perspective of designing general reversal agents for both typical and atypical MDR.
Multidrug resistance (MDR) is defined as resistance of tumor cells to the cytotoxic action of multiple structurally dissimilar and functionally divergent drugs commonly used in chemotherapy. 1,4-Dihydropyridines (DHP(s)) are one of the major classes of Ca2+ channel blockers, and it has been shown that these agents are a new class of drug resistance reversers in cancer treatment. Analysis of various investigations on MDR reversing effects of DHPs shows that they can be a potential class for designing compounds simultaneously effective on both typical and atypical MDR. Also, it is possible to include some considerations on essential structural features for MDR reversing and further decreasing of Ca2+ channel blocking activity as an adverse effect.
Miri
Ramin
R
Medicinal & Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, PO Box 71345-3288, Shiraz, Iran. mirir@sums.ac.ir
Mehdipour
Ahmadreza
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D004095:Dihydropyridines