Design and Synthesis of Brefeldin A-Isothiocyanate Derivatives with Selectivity and Their Potential for Cervical Cancer Therapy.

Abstract

Brefeldin A has a wide range of anticancer activity against a variety of tumor cells. Its poor pharmacokinetic properties and significant toxicity seriously hinder its further development. In this manuscript, 25 brefeldin A-isothiocyanate derivatives were designed and synthesized. Most derivatives showed good selectivity between HeLa cells and L-02 cells. In particular, 6 exhibited potent antiproliferative activity against HeLa cells (IC50 = 1.84 μM) with no obvious cytotoxic activity to L-02 (IC50 > 80 μM). Further cellular mechanism tests indicated that 6 induced HeLa cell cycle arrest at G1 phase. Cell nucleus fragmentation and decreased mitochondrial membrane potential suggested 6 could induce apoptosis in HeLa cells through the mitochondrial-dependent pathway.

• Authors: Mingying Wang, Xiaoyuan Chen, Ying Qu, Qingyinglu Ma, Huaqi Pan, Haonan Li, Huiming Hua, Dahong Li
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 28 Issue 11 (May 23 2023) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 37298761 (Publication Type: Journal Article)

Chemical References

• Brefeldin A
• Antineoplastic Agents
• Isothiocyanates

Topics

• Female
• Humans
• HeLa Cells
• Uterine Cervical Neoplasms (drug therapy, metabolism)
• Brefeldin A (pharmacology, therapeutic use)
• Cell Proliferation
• Antineoplastic Agents
• Apoptosis
• Isothiocyanates (pharmacology, therapeutic use)
• Drug Screening Assays, Antitumor
• Cell Line, Tumor
• Structure-Activity Relationship