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<p>A novel series of aryloxazole–1,3,5-triazin-2-yl furo[2,3-d]pyrimidine derivatives (<b>24a–j</b>) 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 <b>24a–24e</b> demonstrated superior potency relative to etoposide. Among them, compound <b>24a</b>, 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&#xa0;µM, 0.18 ± 0.046&#xa0;µM, 0.23 ± 0.066&#xa0;µM, and 1.09 ± 0.73&#xa0;µM, respectively. Docking simulations highlighted compounds <b>24a</b> and <b>24b</b> 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 <b>24a</b>. 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.</p> Graphical abstract <p>The 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.</p> <p></p>

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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 derivatives

  • 期刊论文

  • 发表日期：

    2026年5月11日

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  • Pulapaka Sravani Kumari,
  • Reddymasu Sreenivasulu,
  • S. V. S. R. Krishna Bandaru,
  • Swathi Thumula,
  • Ravikumar Kapavarapu,
  • Medikonda Manoranjani

摘要

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 abstract

The 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.