Synthesis, Molecular Docking Studies and ADME Prediction of Some New Albendazole Derivatives as α-Glucosidase Inhibitors.

A series of novel 2-(substituted arylidene)-N-(5-(propylthio)-2,3-dihydro-1H-benzo[d]imidazol-2-yl)hydrazine-1-carboxamide derivatives 3a-i were synthesized via condensation of N-(5-(propylthio)-1H-benzo[d]imidazol-2-yl) hydrazinecarboxamide (2), with the corresponding ketone or aldehydes. The chemical structures of the compounds prepared were confirmed by analytical and spectral data. The compounds were screened for their α-glucosidase inhibitory activity and all of them showed better inhibition than acarbose, except 3h. In particular, compound 3a proved to be the most active compound among all synthetic derivatives having IC50 value 12.88±0.98 µM. Also, molecular docking studies were carried out for the compounds to figure out the binding interactions. Compound 3a has exhibited the highest binding energy (ΔG = -9.4 kcal/mol) and the most hydrogen bond interactions with active sites. Eventually, in silico studies were in good agreement with in vitro studies.

Design, Synthesis, and Molecular Docking Studies of a Conjugated Thiadiazole-Thiourea Scaffold as Antituberculosis Agents.

In view of the emergence and frequency of multidrug-resistant and extensively drug-resistant tuberculosis and consequences of acquired resistance to clinically used drugs, we undertook the design and synthesis of novel prototypes that possess the advantage of the two pharmacophores of thiourea and 1,3,4-thiadiazole in a single molecular backbone. Three compounds from our series were distinguished from the others by their promising activity profiles against Mycobacterium tuberculosis strain H37Rv. Compounds 11 and 19 were the most active representatives with minimum inhibitory concentration (MIC) values of 10.96 and 11.48 µM, respectively. Compound 15 was shown to inhibit M. tuberculosis strain H37Rv with an MIC value of 17.81 µM. Cytotoxicity results in the Vero cell line showed that these three derivatives had selectivity indices between 1.8 and 8.7. In order to rationalize the biological results of our compounds, molecular docking studies with the enoyl acyl carrier protein reductase (InhA) of M. tuberculosis were performed and compounds 11, 15, and 19 were found to have good docking scores in the range of -7.12 to -7.83 kcal/mol.