Mechanism of unusual formation of 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones and 4-oxo-4H-chromene-3-carbothioic acid N-phenylamides and their antimicrobial evaluation

• Published in: European journal of medicinal chemistry 2009-08, Vol.44 (8), p.3209-3216
• Main Authors: RAJ, Tilak, RICHA KAUR BHATIA, RAKESH KUMAR SHARMA, GUPTA, Vivek, SHARMA, Deepak, SINGH ISHAR, Mohan Paul
• Format: Article
• Language: English
• Subjects: Amides - chemistry; Amides - pharmacology; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Bacteria - drug effects; Biological and medical sciences; Chromones - chemistry; Crystallography, X-Ray; Fungi - drug effects; Medical sciences; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Spectrum Analysis; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.03.030

6/6,7-Substituted 3-formylchromones (9a-e) react with 2 equivalents of 2-phenyl-4-dimethylamino-1-thia-3-azabuta-1,3-diene (10) or thiobenzamide (11) in refluxing toluene to furnish novel substituted 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones (12a-e). However, reactions of substituted 2-anilino-3-formylchromones (15a-d) with thiobenzamide (11, 2 equivalents) in refluxing xylene furnish 4-oxo-4H-chromene-3-carbothioic acid N-phenylamide (17a-d) in high yields. A mechanistic rationalization of the conversion of 2-anilino-3-formylchromones (15a-d) to N-phenylamides (17a-d), and 3-formylchromones (9a-e) to the corresponding thioaldehydes, is proffered. All the compounds (12a-e, 17a-d) display very high antifungal and antibacterial activities against a number of strains. Dithiazole 12d exhibits a very high antifungal activity (MIC 5 microg/ml) against Geotrichum candidum, better than fluconazole (MIC 09 microg/ml) and also possesses good antibacterial activity (MIC 52 microg/ml) against Shigella flexneri.