Vol. 7, Issue 1, Part A (2025)

Tuberculosis (TB) caused by Mycobacterium tuberculosis, is one of the leading infectious diseases in humans that has led to 1.5 million deaths in the year 2020. Hence it is required to develop novel compounds possessing antimycobacterial properties to enhance current therapies. Recently, a key area of research focus is the advancement of novel adamantane based drug molecules with enhanced pharmacokinetic and pharmacodynamic properties. The adamantyl moiety is well established as a crucial pharmacophore in biologically active compounds. Incorporating the adamantyl core into molecules can significantly influence their lipophilicity, pharmacological, and biological properties.

On the light of the above points, two adamantane hydrazide hydrazone derivatives namely N’-(5-Bromo-4-hydroxy-3-methoxybenzylidene) adamantane-1-carbohydrazide (5-BVAC) and N’-(4-hydroxy-3-methoxy-5-nitro benzylidene) adamantane-1-carbohydrazide (5-NVAC) were synthesised and tested against a susceptible strain of Mycobacterium tuberculosis (H37Rv). The derivatives showed significant antituberculosis activity when compared with known antituberculosis drug Isoniazid.

The in silico study was carried with MmpL3 from M. smegmatis which has the similar genus as Mycobacterium tuberculosis (H37Rv). The results show that newly synthesised derivatives to be a new inhibitor of MmpL3 with the binding mode similar to that of other antituberculars that target MmpL3.