Synthesis, antitubercular, antimicrobial activities and molecular docking study of quinoline bearing dihydropyrimidines.

In order to develop the antimicrobial and antitubercular agents, we have derived quinoline bearing dihydropyrimidine analogues 5a-o and structures of these compounds were determined by spectroscopic techniques. Further, we have calculated the molecular properties prediction and drug-likeness by Molinspiration property calculation toolkit and MolSoft software, respectively. The most active compound against Mycobacterium tuberculosis (5m, MIC = 0.20 µg/mL) also possessed a maximum drug-likeness model score (0.42). Compounds 5m, 5g and 5k were possessed promising antibacterial activity against tested bacterial species. Compound 5k was the only compound to have eye-catcher antifungal activity. Furthermore, the MTT cytotoxicity results on HeLa cells suggested lower cytotoxicity of biologically active compounds. Supramolecular interactions of the synthesized compounds has been assessed my means of molecular docking studies. Although all the synthesized compounds are showing preferably good interactions with their respective proteins, their binding free energies values suggest that these molecules are preferred for antitubercular activity rather than antimicrobial activity.

Design and synthesis of novel (Z)-5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-3-((1-substituted phenyl-1H-1,2,3-triazol-4-yl)methyl)thiazolidine-2,4-diones: a potential cytotoxic scaffolds and their molecular modeling studies.

In an effort to discover potential cytotoxic agents, a series of novel (Z)-5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-3-((1-substituted phenyl-1H-1,2,3-triazol-4-yl)methyl)thiazolidine-2,4-dione derivatives (8a-n) were designed and synthesized in various steps with acceptable reaction procedures with quantitative yields and characterized by 1H NMR, 13C NMR, IR, HRMS and ESI-MS spectra. These newly synthesized novel derivatives were screened for their in vitro cell viability/cytotoxic studies against human breast cancer cell line (MCF-7) with various concentrations of 0.625 µM, 1.25 µM, 2.5 µM, 5 µM and 10 µM, respectively. The biological interpretation assay outcome was demonstrated in terms of cell viability percentage reduction and IC50 values against standard reference drug cisplatin. Based on these results, most of the derivatives exhibited promising cytotoxic activity. Among them, particularly compounds 8j (R1 = OMe and R3 = NO2) and 8e (R3 = CF3) demonstrate remarkable cytotoxic activity with IC50 values 0.426 µM ± 0.455 and 0.608 µM ± 0.408, which are even better than the standard drug cisplatin 0.636 µM ± 0.458 and compounds 8m (R2 = OMe and R3 = OMe) and 8c (R3 = OMe) exhibited closely equivalent IC50 values to the standard drug with IC50 values 0.95 µM ± 0.32 and 0.976 µM ± 0.313 and rest of the compounds exhibits moderate cytotoxic activity. Moreover, molecular modeling studies and ADME calculations of the novel synthesized derivatives are in adequate consent with the pharmacological screening results.