Effects of 12 Ca2+ antagonists on multidrug resistance, MDR1-mediated transport and MDR1 mRNA expression

Differential effects of calcium antagonists on ABCG2/BCRP-mediated drug resistance and transport in SN-38-resistant HeLa cells

“…Katoh et al (21) demonstrated that benidipine and nicardipine strongly inhibited ABCB1/MDR1, whereas nifedipine showed weak activity among the 13 dihydropyridine calcium antagonists used. In addition, the reversal effects of calcium antagonists on resistance to the ABCB1/ MDR1 substrate, i.e., vinblastine or paclitaxel, have been reported using ABCB1/MDR1-overexpressing cells, demonstrating inhibitory activity as follows: verapamil > benidipine > nicardipine > diltiazem > nifedipine ≈ nisoldipine ≈ nitrendipine (11). In the same study, the inhibitory activity on ABCB1/ MDR1-mediated transport was ranked as follows: nicardipine ≈ benidipine > verapamil > nisoldipine > nitrendipine > diltiazem > nifedipine (11).…”

“…In addition, the reversal effects of calcium antagonists on resistance to the ABCB1/ MDR1 substrate, i.e., vinblastine or paclitaxel, have been reported using ABCB1/MDR1-overexpressing cells, demonstrating inhibitory activity as follows: verapamil > benidipine > nicardipine > diltiazem > nifedipine ≈ nisoldipine ≈ nitrendipine (11). In the same study, the inhibitory activity on ABCB1/ MDR1-mediated transport was ranked as follows: nicardipine ≈ benidipine > verapamil > nisoldipine > nitrendipine > diltiazem > nifedipine (11). Collectively, benidipine and nicardipine were suggested to have strong inhibitory activity on both ABCG2/ BCRP and ABCB1/MDR1, but nifedipine had weak activity on both (Table III).…”

“…In 1981, the inhibitory effect of verapamil on ABCB1/MDR1 function was reported (6), and then, the effects of calcium antagonists on ABCB1/MDR1 were extensively investigated (7)(8)(9)(10). We also examined the effects of calcium antagonists on ABCB1/MDR1-mediated transport and resistance, which varied according to the type of calcium antagonist used (11). However, little information is available concerning the effects of calcium antagonists on ABCG2/BCRP.…”

Reactions of 26-Iodopseudodiosgenin and 26-Iodopseudodiosgenone with Various Nucleophiles and Pharmacological Activities of the Products

“…The reactions of 8 with diethyl amine, pyrrolidine, piperidine, morphorine and 1-methylpiperazine (runs 4-8, respectively) gave the corresponding amines 16-20 in yields of 58, 70, 80, 54 and 62%, respectively. The reactions of 9 with diethyl amine, pyrrolidine, piperidine, morphorine and 1-methylpiperazine (runs 15-19, respectively) gave compounds (21)(22)(23)(24)(25) in 64, 27, 79, 73 and 61% yields, respectively. The reaction of 8 with imidazole in the presence of K 2 CO 3 (run 9) gave (26) and 10 in 33 and 47% yields, respectively, and that of 9 with imidazole in the presence of K 2 CO 3 (run 20) gave (27) and 11 in 18 and 27% yields, respectively.…”

“…20) P-gp acts as an efflux pump to remove several antitumor agents, Ca ϩ antagonists, cyclosporine, digoxin and other compounds from cells. 21) The cytotoxic activity of each pseudodiosgenin and pseudodiosgonone derivative was estimated by MTT assay, 22) and IC 50 values calculated based on the percent inhibition of growth are listed in Tables 2 and 3, respectively. First, the effects on HCT 116 cells of pseudodiosgenins 2, 4, 10, 12, 16-20 and 26 (Table 2) were compared with those of pseudodiosgenones 3, 5, 11, 13, 21-25 and 27 (Table 3) which had the same side chain structures as the corresponding pseudodiosgenins. Among the pseudodiosgenins, only 2, 4 and 12 showed strong cytotoxic activity (IC 50 values: 2.6Ϯ0.3-6.7Ϯ1.4 mM).…”