Optimization of Thiazolidone Scaffolds Using Pocket Modeling for Development of Potential Secretory System Inhibitors of Mycobacterium tuberculosis

Turkish Journal of Pharmaceutical Sciences

article

Shivratna V. KHARE¹  Sujata P. CHOUDHARI²  Siddharth P. PHALLE¹  Santosh S. KUMBHAR¹  Prafulla B. CHOUDHARI¹  Sambhaji R. MASAL¹  Aakash K. PATIL¹  Rakesh P. DHAVALE³  Durgacharan A. BHAGWAT³  Atul M. KADAM⁴ 

[1] Bharati Vidyapeeth College of Pharmacy, Department of Pharmaceutical Chemistry, Computational Chemistry Research Lab;Sarojini College of Pharmacy, Department of Pharmaceutical Analysis;Bharati Vidyapeeth College of Pharmacy, Department of Pharmaceutics;Shree Santkrupa College of Pharmacy, Department of Pharmaceutics

关键词: Mycobacterium tuberculosis;    Sec;    ESX;    docking;    antimycobacterial;    multidrug resistant;    pocket modeling;   

DOI  :  10.4274/tjps.galenos.2018.12599

来源: Galenos Yayinevi

【 摘 要 】

Objectives: Mycobacterium tuberculosis is the causative organism of tuberculosis, which is the most lethal disease after cancer in the current decade. The development of multidrug and broadly drug-resistant strains is making the problem of tuberculosis more and more critical. In the last 40 years, only one molecule has been added to the treatment regimen. Generally, drug design and development programs target proteins whose function is known to be essential to the bacterial cell. M. tuberculosis possesses specialized protein export systems like the SecA2 export pathway and ESX pathways. Materials and Methods: In the present communication, rational development of an antimycobacterial agent’s targeting protein export system was carried out by integrating pocket modeling and virtual analysis. Results: The 23 identified potential lead compounds were synthesized, characterized by physicochemical and spectroscopic methods like infrared and nuclear magnetic resonance spectroscopy, and further screened for antimycobacterial activity using isoniazid as standard. All the designed compounds showed profound antimycobacterial activity. Conclusion: We found that Q30, M9, M26, U8, and R26 molecules had significant desirable biological activity and specific interactions with Sec of mycobacteria. Further optimization of these leads is necessary for the development of potential antimycobacterial drug candidates with fewer side effects.

【 授权许可】

Unknown