Synthesis, evaluation and modeling of some triazolothienopyrimidinones as anti-inflammatory and antimicrobial agents

• Published in: Future medicinal chemistry 2017-06, Vol.9 (9), p.881-897
• Main Authors: Bekhit, Adnan A, Farghaly, Ahmed M, Shafik, Ragab M, Elsemary, Mona MA, El-Shoukrofy, Mai S, Bekhit, Alaa El-Din A, Ibrahim, Tamer M
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Ulcer Agents - chemical synthesis; Anti-Ulcer Agents - chemistry; Anti-Ulcer Agents - pharmacology; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Candida albicans - drug effects; dual anti-inflammatory antimicrobial activities; Escherichia coli - drug effects; human COX-1 and COX-2 enzymatic assay; Male; Microbial Sensitivity Tests; Models, Molecular; molecular modeling studies; Molecular Structure; pyrazole; Rats; Rats, Sprague-Dawley; Staphylococcus aureus - drug effects; Stomach Ulcer - drug therapy; triazolothienopyrimidinone derivatives
• ISSN: 1756-8919; 1756-8927
• DOI: 10.4155/fmc-2016-0242

New triazolotetrahydrobenzothienopyrimidinone derivatives were synthesized. : Their structures were confirmed, and their anti-inflammatory, antimicrobial activities and ulcerogenic potentials were evaluated. Compounds and showed minimal ulcerogenic effect and high selectivity toward human recombinant COX-2 over COX-1 enzyme with IC values of 1.39, 1.22 and 0.56 μM, respectively. Their docking outcome correlated with their biological activity and confirmed the high selectivity binding toward COX-2. Compound displayed antimicrobial activity comparable to that of ampicillin against while compounds and were similar to ampicillin against . In addition, compounds and showed dual anti-inflammatory/antimicrobial activities. This work represents a promising matrix for developing new potential anti-inflammatory, antimicrobial and dual antimicrobial/anti-inflammatory candidates.