Novel Hybrid 1,2,4- and 1,2,3-Triazoles Targeting Mycobacterium Tuberculosis Enoyl Acyl Carrier Protein Reductase (InhA): Design, Synthesis, and Molecular Docking

Abstract

Tuberculosis (TB) caused by Mycobacterium tuberculosis is still a serious public health concern around the world. More treatment strategies or more specific molecular targets have been sought by researchers. One of the most important targets is M. tuberculosis’ enoyl-acyl carrier protein reductase InhA which is considered a promising, well-studied target for anti-tuberculosis medication development. Our team has made it a goal to find new lead structures that could be useful in the creation of new antitubercular drugs. In this study, a new class of 1,2,3- and 1,2,4-triazole hybrid compounds was prepared. Click synthesis was used to afford 1,2,3-triazoles scaffold linked to 1,2,4-triazole by fixable mercaptomethylene linker. The new prepared compounds have been characterized by different spectroscopic tools. The designed compounds were tested in vitro against the InhA enzyme. At 10 nM, the inhibitors 5b, 5c, 7c, 7d, 7e, and 7f successfully and totally (100%) inhibited the InhA enzyme. The IC50 values were calculated using different concentrations. With IC50 values of 0.074 and 0.13 nM, 7c and 7e were the most promising InhA inhibitors. Furthermore, a molecular docking investigation was carried out to support antitubercular activity as well as to analyze the binding manner of the screened compounds with the target InhA enzyme’s binding site.

Synthesis of 1,2,4‐triazole and 1,3,4‐oxadiazole derivatives as inhibitors for STAT3 enzymes of breast cancer

“…5-Arylmethyl-1,3,4-oxadiazole-2-thiols 5a,b were prepared as previously stated by Li et al [14] Compounds 10a,b were synthesized as described by El Sawy et al [15] for the synthesis of 10a and by Deshmukh et al [16] for the synthesis of 10b by refluxing compounds 5a,b with hydrazine hydrate. Compound 10a,b has been previously synthesized by Kamboj et al [17] through a slightly different method by directly refluxing potassium dithiocarbazinate with hydrazine hydrate.…”

Explicit molecular dynamics simulation studies to discover novel natural compound analogues as Mycobacterium tuberculosis inhibitors

“…We further made an analogy with the other compounds retrieved from the recently published literature [ 54 , 55 ]. Correspondingly 20 compounds were sketched on Biovia Draw 2017.…”

Synthesis of novel pyrazolone candidates with studying some biological activities and in-silico studies

“…Molecular docking was analyzed via the CB-Dock server ( http://clab.labshare.cn/cb-dock/php/index.php ) 42 , 43 . CB-Dock2 automatically identifies binding sites, calculates center and size, customizes docking box size based on query ligands, and performs molecular docking with AutoDock Vina 1.1.2.…”