Protein tyrosine phosphatase 1B (PTP1B) is an important target for the treatment of diabetes. A series of thiazolidin‐4‐one derivatives 8–22 was designed, synthesized and investigated as PTP1B inhibitors. The new molecules inhibited PTP1B with IC50 values in the micromolar range. 5‐(Furan‐2‐ylmethylene)‐2‐(4‐nitrophenylimino)thiazolidin‐4‐one (17) exhibited potency with a competitive type of enzyme inhibition. structure–activity relationship studies revealed various structural facets important for the potency of these analogues. The findings revealed a requirement for a nitro group‐including hydrophobic heteroaryl ring for PTP1B inhibition. Molecular docking studies afforded good correlation with experimental results. H‐bonding and π–π interactions were responsible for optimal binding and effective stabilization of virtual protein‐ligand complexes. Furthermore, in‐silico pharmacokinetic properties of test compounds predicted their drug‐like characteristics for potential oral use as antidiabetic agents.Additionally, a binding site model demonstrating crucial pharmacophoric characteristics influencing potency and binding affinity of inhibitors has been proposed, which can be employed in the design of future potential PTP1B inhibitors.
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, with high level of mortality worldwide, currently with approximately 10 million cases of tuberculosis. These rate of incidence are due to several factors such as bacterial resistance, AIDS, latent tuberculosis that reoccur in patient. Deazaflavin dependent nitroreductase (Ddn) is an emerging target in the field of antitubercular agent. Ddn catalyses the reduction of nitroimidazoles resulting in intra-cellular release of lethal reactive nitrogen species. Nitroimidazole class drug- delamanid and pretonamid are used in the treatment of MDR-TB. In this present study, 26 new nitroimidazole derivatives were designed and docked into Ddn enzyme. In docking study, compounds 3, 5, 15, 16, 17, 18 and 21 showed similar interaction with amino acid residues such as Tyr 65, Ser 78, Tyr 136 as pretonamid reference drug and highest docking score and better ADMET compatibility. The ADMET prediction docking study of new designed compound revealed that the compounds 3, 16, 17 and 21 showed good binding with Ddn. In future it may be good and effective lead for development of antitubercular agent.
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