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

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

  • Bioorg Chem. 2025 Oct:165:109072. doi: 10.1016/j.bioorg.2025.109072.
Gang Chen 1,  Shiyi Zhong 2,  Chunxu Zhong 1,  Hongmin Zhang 3,  Ali Raza Ishaq 4,  Yanrong Li 1,  Liuxin Yang 1,  Kai Wang 5,  Jie Pan 6,  Xiang Li 7
Affiliations

Affiliations

  • 1 Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, College of Health Science and Engineering, Hubei University, Wuhan 430062, China.
  • 2 Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, College of Health Science and Engineering, Hubei University, Wuhan 430062, China; Department of Endocrinology, Liangjiang Hospital of Chongqing Medical University, People's Hospital of Chongqing Liangjiang New Area, Chongqing 400000, China.
  • 3 Department of Endocrinology, Liangjiang Hospital of Chongqing Medical University, People's Hospital of Chongqing Liangjiang New Area, Chongqing 400000, China. Electronic address: zhanghongmin0501@163.com.
  • 4 School of Life Science, Hubei University, Wuhan 430062, China.
  • 5 Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, College of Health Science and Engineering, Hubei University, Wuhan 430062, China; Hubei Jiangxia Laboratory, Wuhan 430200, Hubei, PR China. Electronic address: kaiwang@hubu.edu.cn.
  • 6 Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, College of Health Science and Engineering, Hubei University, Wuhan 430062, China. Electronic address: j.pan@hubu.edu.cn.
  • 7 Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, College of Health Science and Engineering, Hubei University, Wuhan 430062, China. Electronic address: lixiang199284@hubu.edu.cn.
PMID: 41066867 DOI: 10.1016/j.bioorg.2025.109072
Abstract

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.

Keywords

Calcium channel blocker; Chemotherapy; Dihydropyridine derivatives; Hypertensive patients; P-glycoprotein.

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