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

Synthesis, in-vitro anticancer evaluation and in-silico molecular docking studies of oxazol-2-yl)pyrazin-2-yl)-5-(pyridin-4-yl)-1,3,4-oxadiazole derivatives

Garikipati Karuna Deepthi, Reddymasu Sreenivasulu, Mandava Bhuvan Tej, Swathi Thumula, Ravi Kumar Kapavarapu, and Mandava Venkata Basaveswara Rao

Department of Chemistry, Krishna University, Machilipatnam, India

E-mail: professormandava@gmail.com

Received: 31 August 2025  Accepted: 20 March 2026

Abstract:

A new series of amide derivatives of oxazol-2-yl)pyrazin-2-yl)-5-(pyridin-4-yl)-1,3,4-oxadiazole derivatives were designed, synthesized and evaluated in-vitro anticancer activities against breast cancer (MCF-7), lung cancer (A549), colon cancer (Colo-205) and ovarian cancer (A2780) by using of MTT assay, and the etoposide used as reference drug. The IC₅₀ values ranges of compound from 0.23 ± 0.045 µM to 7.38 ± 5.62 µM, where etoposide showed values ranges from 0.17 ± 0.034 µM to 3.34 ± 0.152 µM. Most of the tested derivatives were showed good to moderate activities than etoposide. This study investigates the multitarget anticancer potential of compounds 21a–21d through molecular docking and ADME–Tox analysis. The compounds demonstrated strong binding affinities and critical interactions with EGFR and VEGFR2, indicating their potential to modulate key cancer-associated pathways, including proliferation and angiogenesis. ADME–Tox predictions revealed good solubility but identified limitations such as low intestinal absorption, P-gp–mediated efflux, and inhibition of multiple CYP450 isoforms, highlighting the need for further structural optimization. Overall, these findings provide mechanistic insights supporting the potential of this scaffold in multitarget-oriented anticancer drug discovery.

Graphical abstract

Keywords: Zibotentan; Pyrazine; Mubritinib; 1,3-oxazole; Anticancer activity; Molecular docking studies

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-04859-6

Chemical Papers 80 (7) 7837–7856 (2026)