Title:Synthesis, Bioactivity Evaluation, and Molecular Docking Study of
Tranilast Analogs as Anticancer Agents
Volume: 21
Issue: 3
Author(s): Phuong-Thuy T. Phan, Tuan-Anh N. Pham*, Ngoc Phuong Nguyen, Van-Anh Tran Nguyen and Tuyet Hong Nguyen
Affiliation:
- Faculty of Pharmacy, Van Lang
University, Ho Chi Minh City, 70000, Vietnam
Keywords:
Tranilast analogs, anticancer agents, molecular docking, HepG2, MCF-7, TGFβ1.
Abstract: Developing new agents with higher therapeutic potential and less toxicity to overcome the
limitations of chemotherapy in cancer treatment has been identified as an urgent need and priority. Recent
studies have shown promising anticancer activities of tranilast when used alone or in combination
with other chemotherapeutic agents. This research aims to synthesize tranilast analogs, evaluate in
vitro anticancer activity, and dock into the TGFβ1 target to find stronger anticancer agents. Tranilast
(5a) and analogs (5b–f) were synthesized from anthranilic acid derivatives, Meldrum’s acid, and benzaldehydes
based on the Knoevenagel-Doebner reaction. The compounds were evaluated for in vitro
cytotoxicity activity by MTT assay and docked into the TGFβ1 target using AutoDockTools–1.5.6.
Tranilast (5a) and seven analogs (5b–h) were successfully synthesized and analyzed for their structures.
Four analogs (5b–d, 5f) possessed stronger effects on both HepG2 and MCF-7 cell lines with
proliferation inhibitions at concentrations of 100 μg/mL in the range of 41 to 95% compared to
tranilast (16.95% and 22.64%). Compound 5f exhibited the most potent analog with IC50 = 27.57
μg/mL (HepG2) and 16.67 μg/mL (MCF-7) compared to tranilast (IC50 > 100 μg/mL) and had good
binding affinity on TGFβ1 target (docking score ˗7.35 Kcal/mol). Four of seven tranilast analogs possessed
stronger cytotoxicity activity on both HepG2 and MCF-7 cell lines compared to that of the parent
compound, tranilast. Notably, compound 5f displayed the most potent activity and good binding
affinity on the TGFβ1 target, indicating the potential for further study as an anticancer agent.
