Janković, NenadMilović E.Jovanovic, JelenaMarković, ZoranVranes, MilanStanojkovic, TatjanaMatic, IvanaDjordjic Crnogorac, MarijaKlisuric, OliveraCvetinov, MiroslavAbbas Bukhari S.2022-09-132022-09-1320220009-2797https://scidar.kg.ac.rs/handle/123456789/14987In order to discover new dual-active agents, a series of novel Biginelli hybrids (tetrahydropyrimidines) and their ruthenium(II) complexes were synthesized. Newly synthesized compounds were characterized by IR, NMR, and X-ray techniques and investigated for their cytotoxic effect on human cancer cell lines HeLa, LS174, A549, A375, K562 and normal fibroblasts (MRC-5). For further examination of the cytotoxic mechanisms of novel complexes, two of them were chosen for analyzing their effects on the distribution of HeLa cells in the cell cycle phases. The results of the flow cytometry analysis suggest that the proportion of cells in G2/M phase was decreased following the increase of subG1 phase in all treatments. These results confirmed that cells treated with 5b and 5c were induced to undergo apoptotic death. The ruthenium complexes 5a-5d show significant inhibitory potency against SARS-CoV-2 Mpro. Therefore, molecule 5b has significance, while 5e possesses the lowest values of ΔGbind and Ki, which are comparable to cinanserin, and hydroxychloroquine. In addition, achieved results will open a new avenue in drug design for more research on the possible therapeutic applications of dual-active Biginelli-based drugs (anticancer-antiviral). Dual-active drugs based on the hybridization concept “one drug curing two diseases” could be a successful tactic in healing patients who have cancer and the virus SARS-CoV-2 at the same time.restrictedAccessarticle10.1016/j.cbi.2022.1100252-s2.0-85132880263