Novel dihydropyridines as potential calcium-channel and P-glycoprotein blockers applicable for chemotherapy sensitization.

P-glycoprotein (P-gp)-mediated multidrug resistance in tumors is one of the main reasons for chemotherapy failure. For hypertensive patients undergoing long-term chemotherapy, antihypertensive drugs with P-gp inhibitory effects are expected to substantially reduce the dosage of chemotherapeutic agents. 1,4-Dihydropyridines (DHPs), as classical calcium channel blockers, have been widely used in clinical hypertension treatment. In this study, novel dihydropyridines, namely HCAs, were designed and evaluated for their ability to reverse multidrug resistance. HCAs exerted synergistic effects on calcium channels and P-gp, potentially alleviating hypertension while sensitizing tumors to chemotherapy. Low concentrations of HCAs significantly enhanced the sensitivity of tumor cells to cisplatin; notably, 2 μM HCA-6 increased the inhibitory effect of cisplatin on HeLa cells by 61.21 %. Overall, HCAs hold promises for benefiting hypertensive patients with long-term cancer conditions and reducing reliance on high-dose chemotherapeutic agents.