ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Design, synthesis, and biological evaluation of pirfenidone-based compounds against breast cancer

Raghavendra Hegde, Itte Pushpavathi, B. N. Nippu, and T. M. Madhukumar

Department of P.G Studies and Research in Industrial Chemistry, Jnana Sahyadri, Kuvempu University, Shankaraghatta, Shivamogga, India

E-mail: ittepushpa.chem@gmail.com

Received: 2 March 2025  Accepted: 13 October 2025

Abstract:

This current study explores the synthesis and anticancer efficacy of novel Pirfenidone related molecules targeting the MCF7 breast cancer cell line. A series of Pirfenidone derivatives (PA1-6) were designed and synthesized. Initial computational analyses, including pharmacokinetic profiling and docking screenings, were executed to evaluate the interaction of these derivatives with VEGFR-2 kinase, a crucial target in cancer progression. Following in silico explorations, the synthesized derivatives underwent in vitro testing to determine their cytotoxic effects and establish IC₅₀ values. Results indicated that the derivatives exhibited varying levels of efficacy, with PA2 demonstrating the highest potency (IC₅₀ = 15.25 ± 3.02 µM). Structure–activity relationship (SAR) analysis highlighted the influence of substituents on the phenyl ring in modulating anticancer activity. Additionally, flow cytometry analysis suggested that PA2 induces apoptosis in the S phase of the cell cycle. Overall study underscores the therapeutic potential of Pirfenidone derivatives as promising candidates for breast cancer treatment.

Keywords: Pirfenidone; HATU; Anticancer; MCF7; Molecular docking; VEGFR-2

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04448-z

Chemical Papers 80 (2) 1241–1250 (2026)