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

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 16; p. 3570
• Main Authors: Bhat, Mashooq A, Al-Omar, Mohamed A, Naglah, Ahmed M, Khan, Azmat Ali
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.08.2020; MDPI
• Subjects: 4-thiazolidinones; Acetic acid; Acids; Aldehydes; antimycobacterial activity; Antitubercular agents; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Antitubercular Agents - toxicity; Aromatic compounds; Bacillus Calmette-Guerin vaccine; BCG; Cancer; Cell Line, Tumor; Cell lines; Chemistry Techniques, Synthetic; Cytotoxicity; cytotoxicity study; Drug development; Drug resistance; HIV; Human immunodeficiency virus; Humans; Hybrids; Metabolism; Mycobacterium bovis - drug effects; Mycobacterium tuberculosis - drug effects; Oral administration; Oxazoles - chemical synthesis; Oxazoles - chemistry; Oxazoles - pharmacology; Oxazoles - toxicity; Structure-Activity Relationship; sulfamethaoxazole; Thiazolidines - chemistry; Tuberculosis; 4-thiazolidinones; cytotoxicity study; antimycobacterial activity; sulfamethaoxazole
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25163570

A search for potent antitubercular agents prompted us to design and synthesize sulfamethaoxazole incorporated 4-thiazolidinone hybrids ( - ) by using a cyclocondensation reaction between 4-amino- -(5-methylisoxazol-3-yl)benzenesulfonamide ( ), aryl aldehyde ( - ), and mercapto acetic acid ( ) resulting in good to excellent yields. All the newly synthesized 4-thiazolidinone derivatives were screened for their in vitro antitubercular activity against and ( strains. The compounds , , , , and revealed promising antimycobacterial activity against and strains with IC 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.