Dihydropyrimidinones: efficient one-pot green synthesis using Montmorillonite-KSF and evaluation of their cytotoxic activity. Issue 69 (23rd November 2020)

• Record Type: Journal Article
• Authors: Farooq, Saleem; Alharthi, Fahad A.; Alsalme, Ali; Hussain, Aashiq; Dar, Bashir A.; Hamid, Abid; Koul, S.
• Is Part Of: RSC advances. Volume 10:Issue 69(2020)
• Page Start: 42221
• Page End: 42234
• Publication Date: 2020-11-23
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0ra09072g
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : The general method for the preparation of DHPM analogs; cytotoxic activity and binding mode of the most active derivative against PI3Kγ and CDK2 targets. Abstract : A simple, efficient, cost-effective, recyclable and green approach has been developed for the synthesis of new dihydropyrimidinone analogs via the Biginelli reaction. The methodology involves a multicomponent reaction catalyzed by "HPA-Montmorillonite-KSF" as a reusable and heterogeneous catalyst. This method gives an efficient and much improved modification of the original Biginelli reaction, in terms of yield and short reaction times under solvent free conditions. All the derivatives were subjected to cytotoxicity screening against a panel of four different human cancer cell lines viz . colon (Colo-205), prostate (PC-3), leukemia (THP-1) and lung (A549) to check their effect on percentage growth. MTT [3-(4, 5-dimethylthiazol-yl)-diphenyl tetrazoliumbromide] cytotoxicity assay was employed to check IC50 values. Of the synthesized analogs, 16a showed the best activity with IC50 of 7.1 ± 0.8, 13.1 ± 1.4, 13.8 ± 0.9 and 14.7 ± 1.1 μM against lung (A549), leukemia (THP-1), prostate (PC-3) and colon (Colo-205) cancer lines, respectively. The 16a analog was further checked for its effect on cancer cell properties through clonogenic (colony formation) and scratch motility (wound healing) assays and thereby was found that it reduced both the colony formation and migratory properties of the lung cancer cell line (A549). Further, molecular docking studies were performed with 16a to show its binding mode.