Development of 'S', 'N' Heterocycles as Antimycobacterials Targeting Fatty Acid Biosynthesis

• Published in: Current computer-aided drug design Vol. 16; no. 6; p. 718
• Main Authors: Dahiwade, Lalita K, Rochlani, Sneha P, Choudhari, Prafulla B, Dhavale, Rakesh P, More, Harinath N
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2020
• Subjects: heterocyclic; isoniazid; molecular docking; Mycobacterium tuberculosis; InhA; Antitubercular
• ISSN: 1875-6697
• DOI: 10.2174/1573409915666191017150843

Mycobacterium tuberculosis is a causative organism of tuberculosis, which is the most deadly disease after cancer in the current decade. The development of multidrug and broadly drug- resistant strains makes the tuberculosis problem more and more critical. In the last 40 years, only one molecule is added to the treatment regimen. Generally, drug design and development programs are targeted proteins whose function is known to be essential to the bacterial cell. Here are the development of 'S', 'N' heterocycles as antimycobacterials targeting fatty acid biosynthesis are reported. In the present communication, rational development of anti-mycobacterial agent's targeting fatty acid biosynthesis has been done by integrating the pocket modeling and virtual analysis. The identified potential 33 lead compounds were synthesized, characterized by physicochemical and spectroscopic methods like IR, NMR spectroscopy and further screened for antimycobacterial activity using isoniazid as standard. All the designed compounds have shown profound antimycobacterial activity. In this present communication, we found that 3c, 3f, 3l and 4k molecules had expressive desirable biological activity and specific interactions with fatty acids. Further optimization of these leads is necessary for the development of potential antimycobacterial drug candidates having fewer side effects.