Synthesis of Novel Sulfamethaoxazole 4-Thiazolidinone Hybrids and Their Biological Evaluation.

Azmat Ali Khan,Ahmed M Naglah,Mashooq A Bhat,Mohamed A Al-Omar

doi:10.3390/molecules25163570

Azmat Ali Khan, Ahmed M Naglah + Show 2 more

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https://doi.org/10.3390/molecules25163570

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Abstract

A search for potent antitubercular agents prompted us to design and synthesize sulfamethaoxazole incorporated 4-thiazolidinone hybrids (7a–l) by using a cyclocondensation reaction between 4-amino-N-(5-methylisoxazol-3-yl)benzenesulfonamide (4), aryl aldehyde (5a–l), and mercapto acetic acid (6) resulting in good to excellent yields. All the newly synthesized 4-thiazolidinone derivatives were screened for their in vitro antitubercular activity against M. Bovis BCG and M. tuberculosis H37Ra (MTB) strains. The compounds 7d, 7g, 7i, 7k, and 7l revealed promising antimycobacterial activity against M. Bovis and MTB strains with IC90 values in the range of 0.058–0.22 and 0.43–5.31 µg/mL, respectively. The most active compounds were also evaluated for their cytotoxicity against MCF-7, HCT 116, and A549 cell lines and were found to be non-cytotoxic. Moreover, the synthesized compounds were also analyzed for ADME (absorption, distribution, metabolism, and excretion) properties and showed potential as good oral drug candidates.

Highlights

Tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis (MTB) is one of the most infectious causes of mortality worldwide [1]
Bacillus Calmette-Guerin (BCG) is an attenuated derivative of a virulent strain of Mycobacterium bovis which has been used as a vaccine against MTB, as a recombinant vehicle for multivalent vaccines against other infectious diseases, and as cancer immunotherapy [5]
Compounds (7a–l) were prepared from a cyclocondensation is reported in Schemes 1 and 2

Summary

Introduction

Tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis (MTB) is one of the most infectious causes of mortality worldwide [1]. The pathogenic synergy between TB and HIV is alarming. TB frequently occurs in human immunodeficiency virus (HIV)/AIDS patients [2,3]. In 2019, according to the World Health Organization (WHO), 1.5 million deaths were reported due to TB, out of which 0.36 million people were infected with both HIV and TB. The proportion of new cases with multidrug-resistant tuberculosis (MDR-TB) was 3.5% and has not changed in comparison to recent years [4]. Bacillus Calmette-Guerin (BCG) is an attenuated derivative of a virulent strain of Mycobacterium bovis which has been used as a vaccine against MTB, as a recombinant vehicle for multivalent vaccines against other infectious diseases, and as cancer immunotherapy [5]

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