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

• Main Authors: Mashooq A. Bhat, Mohamed A. Al-Omar, Ahmed M. Naglah, Azmat Ali Khan
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: Molecules
• Subjects: 4-thiazolidinones; sulfamethaoxazole; antimycobacterial activity; cytotoxicity study
• Online Access: https://www.mdpi.com/1420-3049/25/16/3570

A search for potent antitubercular agents prompted us to design and synthesize sulfamethaoxazole incorporated 4-thiazolidinone hybrids (<b>7a</b>–<b>l</b>) by using a cyclocondensation reaction between 4-amino-<i>N</i>-(5-methylisoxazol-3-yl)benzenesulfonamide (<b>4</b>), aryl aldehyde (<b>5a</b>–<b>l</b>), and mercapto acetic acid (<b>6</b>) resulting in good to excellent yields. All the newly synthesized 4-thiazolidinone derivatives were screened for their in vitro antitubercular activity against <i>M. Bovis BCG</i> and <i>M. tuberculosis H37Ra</i> (<i>MTB)</i> strains. The compounds <b>7d</b>, <b>7g</b>, <b>7i</b>, <b>7k</b>, and <b>7l</b> revealed promising antimycobacterial activity against <i>M. Bovis</i> and <i>MTB</i> 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.