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  3. Synthesis of Isosteviol derivatives as potential anticancer agents, especially for ovarian Cancer: In vitro cytotoxicity, cell cycle arrest, network pharmacology and molecular docking study

Synthesis of Isosteviol derivatives as potential anticancer agents, especially for ovarian Cancer: In vitro cytotoxicity, cell cycle arrest, network pharmacology and molecular docking study

  • Bioorg Med Chem Lett. 2025 Aug 15:124:130261. doi: 10.1016/j.bmcl.2025.130261.
Yuxin Ding 1,  Enxiao Wang 1,  Lin Xing 1,  Chaoyan Zhang 1,  Ruilong Sheng 2,  Wenhui Wu 1,  Ruihua Guo 3
Affiliations

Affiliations

  • 1 College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
  • 2 CQM - Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal. Electronic address: ruilong.sheng@staff.uma.pt.
  • 3 College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Department of Marine Biopharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Marine Biomedical Science and Technology Innovation Platform of Lin-gang Special Area, Shanghai 201306, China. Electronic address: rhguo@shou.edu.cn.
PMID: 40311784 DOI: 10.1016/j.bmcl.2025.130261
Abstract

Isosteviol is a tetracyclic diterpenoid from the hydrolysis of steviosidic acid, it exhibits a moderate inhibitory impact on tumor proliferation across various Cancer types. Herein, we improved antitumor efficacy of isosteviol by modifying its reactive groups at C-16 and C-19 positions. A series of isosteviol derivatives 2-17, were synthesized and characterized. Their anti-proliferative activities were evaluated in three human Cancer cell lines (HCT116, SKOV3 and HepG2) by CCK-8 assay. The results showed that derivative 10 has strong Cancer cell inhibitory activities (with IC50 = 24.98 ± 1.82 μM for HCT116, IC50 = 26.15 ± 0.05 μM for SKOV3 and IC50 = 23.09 ± 0.31 μM for HepG2 cells). Accordingly, structure-activity relationships (SARs) of these isosteviol derivatives in ovarian Cancer SKOV3 cells were discussed in detail. Moreover, derivative 10 has concentration-dependent cell cycle arrest at S-G2/M phases in SKOV3 cells, and it could greatly induce Apoptosis. In addition, the targets of isosteviol against ovarian Cancer were predicted and analyzed via network pharmacology. Then, molecular docking analysis showed that derivative 10 could interact with HSP90AA1 through its LYS-58 residues (docking energy: -8.96 kal/mol). The results suggested that derivative 10 might be employed as a promising drug candidate for Anticancer chemotherapy.

Keywords

Anticancer; Cell cycle; HSP90AA1; Isosteviol; Molecular docking; Ovarian; Structure-activity relationships.

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