Gang Chen, Shiyi Zhong, Chunxu Zhong, Hongmin Zhang, Ali Raza Ishaq, Yanrong Li, Liuxin Yang, Kai Wang, Jie Pan, Xiang Li
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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.
期刊介绍：
Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry.
For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature.
The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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