Green approach for the synthesis of novel spiro quinoxaline-pyrimidone based heterocyclic compounds as anticancer agents. (2022)

• Record Type: Journal Article
• Authors: Dabhi, Ravi A.; Dhaduk, Milan P.; Bhatt, Vaibhav D.; Bhatt, Bhupesh S.
• Is Part Of: Materials today. Volume 65:Part 1(2022)
• Page Start: 367
• Page End: 374
• Publication Date: 2022
• Subjects: Multi component reaction -- DNA/BSA binding -- 1 BNA -- Pharmacokinetic study -- MCF-7 cell line; Materials science -- Congresses -- Periodicals; 620.1
• DOI: 10.1016/j.matpr.2022.06.374
• Languages: English
• ISSNs: 2214-7853

Abstract

Highlights: Series of spiro quinoxaline-pyrimidone based heterocyclic compounds (RD1–RD12) were synthesized with green catalyst. The compounds were screened for biomolecular interactions and medicinal activities. Molecular docking study of all the compounds with 1 BNA and BSA (4F5S) was carried out. ADME study of all the synthesized were also carried out. All the compounds have good pharmacokinetic profile. Abstract: Spiro heterocyclic compounds are found to behave as biologically active agents due to their conformational features. The spiro quinoxaline-pyrimidone based heterocyclic compounds (RD 1–RD 12) were synthesized using green catalyst potash alum and structurally characterized using proton NMR, IR, and mass spectral analysis. Antimicrobial activity was performed against five different bacteria to find minimum inhibitory concentration, and it was obtained in the range of 105–240 µM. Compound (RD 10) was most active against staphylococcus aureus (105 µM). In vitro cytotoxicity assay was carried out on brine shrimp, and LC50 values were observed in between 5.66 and 16.34 µg/mL. The compounds to be potentially active against cancer, the compound should effectively bind with the DNA. The binding affinity of all the compounds with DNA and BSA was determined using absorption titration experiment. The Kb value of compound-DNA and compound-BSA was found 0.42–1.93 × 10 5 M −1 and 0.066–2.97 × 10 4 M −1, respectively. The partial intercalation mode of binding for all the compounds with the CT-DNA was proven by the absorption titration, viscosity measurement, and molecular docking study. Docking study of all the compounds was performed with 1 BNA and BSA (4F5S) using autodock vina software. Docking energy data were found in the range of −6.9 to −9.6 kcal/mol and −6.1 to −10.3 kcal/mol with 1 BNA and BSA, respectively. The pharmacokinetic profile of all the compounds was checked using online platforms SwissADME and admetSAR. Anticancer activity was performed using MTT assay on the MCF-7 cell line and the IC50 values are ranged between 60.72 and 188.29 µg/mL.