ZnCl2 catalyzed new coumarinyl-chalcones as cytotoxic agents

• Published in: Saudi journal of biological sciences Vol. 28; no. 1; pp. 386 - 394
• Main Authors: Sathish Kumar, Konidala, Kotra, Vijay, Phani Kumar Kola, Praveena Devi, CH.B., Anusha, Nutakki, Hari Babu, Bollikolla, Adil, Syed Farooq, Shaik, Mohammed Rafi, Khan, Mujeeb, Al-Warthan, Abdulrahman, Alduhaish, Osamah, Mujahid Alam, M.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-01-2021; Elsevier
• Subjects: Anti-cancer; Coumarinyl chalcones; Docking; Original; Tyrosine kinase; Tyrosine kinase; Docking; Anti-cancer; Coumarinyl chalcones
• ISSN: 1319-562X; 2213-7106
• DOI: 10.1016/j.sjbs.2020.10.020

A new series of coumarin-yl-chalcone derivatives (3a-m) had been designed and synthesized through different reactions such as aromatic addition, cyclization and Claisen-Schmidt reactions in good yields (54–78%). 5-acetyl-4-(2-hydroxyphenyl) -6-methyl-3, 4-dihydropyrimidin-2(1H) -one (1) has been synthesized by multi-component one pot reaction of salicylaldehyde, methyl acetoacetate and urea, which was further reacted with malonic acid employing ZnCl2 catalyst to yield 5-acetyl-4-(4-hydroxy-2-oxo-2H-chromen-8-yl) -6-methyl-3, 4-dihydropyrimidin-2(1H) -one (2). The title compounds (3a-m) were synthesised by reacting 5-acetyl-4-(4-hydroxy-2-oxo-2H-chromen-8-yl) -6-methyl-3, 4-dihydropyrimidin-2(1H)-one (2) with different aromatic aldehydes in the presence of potassium hydroxide. In silico studies, a preliminary screening method for predicting the anti-cancer activity was performed for the synthesized compounds (3a-m) against Src, Alb tyrosine kinase and homology model protein (PDB ID: 4csv). The derivatives 3h and 3m showed moderate binding energies. The in vitro cytotoxic activity was evaluated for the compounds 3h and 3m by using human cancer cell-line morphology and MTT assay against three human cell-lines A549 (Lung), Jurkat (Leukemia) and MCF-7 (Breast). The results indicate that the derivatives 3h and 3m display significant anti-cancer activity, however it was found to be less cytotoxic when compared to the standard used i.e. Imatinib.