Introduction: Compounds containing thiadiazole moiety are cognized to possess with variety of clinical and therapeutic activity. Finding a suitable drug target for newly synthesized compounds remain a major bottle neck in current high throughout medicinal chemistry era.
Aim:To effectively synthesize di substituted thiadiazole com pounds and demonstrate drug target identification using an in silico pharmacophore probing approach. Moreover, we also aim to validate the suitability of identified drug target.
Materials and Methods:A costeffective and environmental friendly chemical synthesis scheme for production of di substituted thiadiazole compounds was employed. Target identification was conducted by Pharmmapper software. Validation was accomplished by performing molecular docking and further Molecular Hydrophobic Potential (MHP) analysis.Results: Pharmacophore probing base approach identified hepatocyte growth factor receptor (cMet) as a suitable biological target for newly synthesized compounds. Binding free energy values indicate that compound 4b, 4e, 4g and 4h has tremendous potential to be further used as lead compound to design selective inhibitors of cMet receptor. MHP data from current study supports the possibility that hydrophobic contacts might act as major factor stabilizing thiadiazole cMet complex. Moreover, in silico observations of current study are in absolute accordance with previously described in vitro and crystallographic analysis.
Conclusion:We demonstrate that thiadiazole compounds synthesized in current investigation has high potential to act in modulation of hepatocyte growth factor receptor (cMet) activity and thereby act as putative therapeutic agent in cancer therapy.[Table/ Fig-1]: Schematic representation of methodology adopted in synthesis of novel thiadiazole derivatives in current study.
A series of novel [4-(1,2,3-thiadiazol-4-yl)phenoxy]methylene anchored 1,3,4-triazoles (8a-h) and 1,3,4-thiadiazoles (9a-i) were synthesized from thiosemicarbazide (7a-j). The structures of these newly synthesized compounds were confirmed on the basis of IR, 1 H-NMR, mass spectral techniques, and elemental analysis. The in vitro antimicrobial screenings of the synthesized compounds were carried out against four bacterial pathogens, namely Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and three fungal pathogens Candida albicans, Aspergillus niger and Aspergillus clavatus, using broth microdilution minimum inhibitory concentration method. The compounds 7d, 7j, 8a, 9a, 9b, and 9i exhibited promising antibacterial activity against the tested strains, whereas some compounds were found to be active against one of the tested bacterial strains.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.