Design, synthesis, in-vitro anticancer evaluation and in-silico molecular docking studies of aryl oxazole-1,3,5-triazin-2-yl) furo[2,3-d] pyrimidine derivativesPulapaka Sravani Kumari, Reddymasu Sreenivasulu, S. V. S. R. Krishna Bandaru, Swathi Thumula, Ravikumar Kapavarapu, and Medikonda Manoranjani Department of Chemistry, Krishna University, Machilipatnam, India
E-mail: drmanoranjani@gmail.com Received: 2 December 2025 Accepted: 9 April 2026 Abstract: A novel series of aryloxazole–1,3,5-triazin-2-yl furo[2,3-d]pyrimidine derivatives (24a–j) was synthesized and structurally characterized using appropriate analytical techniques. All compounds were evaluated for their in vitro anticancer activity against a panel of human cancer cell lines, including prostate (PC3), lung (A549), breast (MCF-7), and ovarian (A2780) cancers, using the MTT assay. The clinically established chemotherapeutic agent etoposide was employed as a positive control. Most derivatives exhibited moderate to strong cytotoxic activity compared with the reference drug. Notably, compounds 24a–24e demonstrated superior potency relative to etoposide. Among them, compound 24a, bearing a 3,4,5-trimethoxy substitution on the aryl moiety linked to the oxazole core, showed remarkable antiproliferative activity against PC3, A549, MCF-7, and A2780 cell lines, with IC₅₀ values of 1.12 ± 0.75 µM, 0.18 ± 0.046 µM, 0.23 ± 0.066 µM, and 1.09 ± 0.73 µM, respectively. Docking simulations highlighted compounds 24a and 24b as the most favorable candidates, showing strong predicted binding interactions and stable orientations within the active sites of EGFR and Aurora kinase A, with slightly stronger affinity toward Aurora kinase A. ADMET profiling indicated that most derivatives exhibit acceptable drug-like properties, including general compliance with Lipinski’s criteria and predicted good gastrointestinal absorption, with the exception of 24a. All compounds were predicted to be P-glycoprotein substrates and potential hERG II inhibitors, suggesting possible concerns related to efflux liability and cardiotoxic risk. Collectively, these results support the promise of this scaffold while emphasizing the need for further structural refinement and experimental validation to improve pharmacokinetic and safety profiles before advancing to preclinical evaluation. Graphical abstractThe compound 24a with 3,4,5-trimethoxy group bearing on the aryl moiety attached to oxazole core unit showed good activity against PC3, A549, MCF7 and A2780 cell lines with IC50 values of 1.12±0.75 μM; 0.18±0.046 μM;0.23±0.066 μM and 1.09±0.73 μM.  Keywords: 5-Methylfuro[2,3-d] pyrimidine; furo[2,3-d] pyrimidine; Mubritinib; 1,3-oxazole; Anticancer activity and molecular docking studies Full paper is available at www.springerlink.com. DOI: 10.1007/s11696-026-04897-0
Chemical Papers 80 (8) 8571–8593 (2026) |
Wednesday, August 26, 2026 
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