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Synthesis and Biological Evaluation of 2-thiazolylimino-5-arylidene-4- thiazolidinone Derivatives as Potent Antimycobacterial Agents

[ Vol. 13 , Issue. 2 ]

Author(s):

Monika Jain, Rohani P. Burman, Villendra S. Negi, Sarbjit S. Jhamb, Alka Mital and Manjinder S. Gill   Pages 105 - 113 ( 9 )

Abstract:


Background: The recent emergence of multi-drug resistant (MDR) and extensively drugresistant (XDR) cases of tuberculosis has lead to the search for new structural classes of anti-TB drugs that can be effective against these strains of Mycobacterium tuberculosis. In the present study a series of 2-thiazolylimino-5-arylidene-4-thiazolidinone derivatives, unsubstituted and mono-substituted with hydroxy, methoxy, fluoro, chloro and nitro groups on the aryl ring were synthesized and assayed for their in vitro antimycobacterial activity against drug-sensitive M. tb H37Rv strain. Methods: In vitro antimycobacterial activity against drug-sensitive M. tb H37Rv strain (susceptible both to rifampicin and isoniazid) was performed and expressed as % inhibition at minimum inhibitory concentration (MIC) values. Compounds were initially tested for IC<sub>99</sub> at a concentration of 6.25 &#181;g/ml in BACTEC-460 TB radiometric system, and Isoniazid (0.1 &#181;g/ml) and rifampicin (2.0 μg/ml) were taken as reference standards. Results: We report the synthesis and antimycobacterial activities of 2- thiazolylimino-5-arylidene-4-thiazolidinone derivatives, expressed as % inhibitions, and their MIC values. All of the above synthesized compounds showed substantial antimycobacterial activity in the preliminary screening, and some of the compounds, 8-14, exhibited excellent antimycobacterial activities (86-98 % inhibition) at 6.25–12.5 &#181;g/ml against drugsensitive M. tb H37Rv strain. Conclusion: The 2-thiazolylimino-5-arylidene-4-thiazolidinone derivatives were identified as a new antitubercular chemical entity in this study. Two of the active compounds, 9 and 14 and their derivatives have been identified as potential lead molecules for further drug development. It was observed that the hydroxyl and bulky alkoxy groups enhance antimycobacterial activity, while a halogen substituent decreases the activity. Further structural optimization and identification of molecules are underway in our laboratory..

Keywords:

Antimycobacterial activity, Mycobacterium tuberculosis, Thiazolidinone derivatives.

Affiliation:

, , , , , Department of Pharmaceutical Technology–Process Chemistry, National Institute of Pharmaceutical Education and Research, Sector- 67, S.A.S. Nagar-160062, India.



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