One-pot sustainable synthesis of novel pyrido[2,3-d]pyrimidinones and their evaluation for antitubercular and anticancer activity

• Sustainable synthesis of twelve novel pyrido[2,3- d ]pyrimidinones under green conditions using ʟ-Proline as a catalyst. • Optimization of the reaction conditions in terms of the activity of the catalyst, solvent and feed ratio of the catalyst. • Evalaution of biological activity of the synthesised pyrido[2,3- d ]pyrimidinones against Mycobacterium tuberculosis H37Ra (ATCC 25,177), MCF-7 (human breast cancer cell line), A549 and NCI-H460 (lung cancer cell line). • Characterization of the products by 1 H NMR, 13 C NMR and HRMS analysis. A novel green protocol for the construction of diversified pyrido[2,3- d ]pyrimidinones was accomplished by a single-pot reaction of aryl aldehydes, Meldrum's acid, thiobarbituric acid, and ammonium acetate/aniline in H 2 O using ʟ-proline as an expeditious reusable catalyst at room temperature (26 °C). Our strategy provides an innovative synthetic avenue for the construction of pyrido[2,3- d ]pyrimidinones, as well as several advantages over traditional methods, including a simple procedure, shorter reaction duration, excellent yields, safe handling, easy workup, catalyst recovery, and environmental compatibility. Furthermore, the synthesised compounds were tested for their impact on different cell lines and microorganisms. Compounds 5d and 5e were particularly effective against Mycobacterium tuberculosis (antitubercular), human breast cancer cells (MCF-7), lung cancer cells (A549 and NCI-H460), and both Gram-positive (S. pyogenes) and Gram-negative (E. coli) bacteria. The derivatives with hydroxyl and nitro substitutions [5e, 5f] showed the highest potency against MCF-7, A549, and NCI-H460 cell lines, with IC 50 values of 3.68–4.36, 3.82–3.41, and 11.34–12.28 µg/mL, respectively.