Synthesis and biological evaluation of some thiazolylpyrazole derivatives as dual anti-inflammatory antimicrobial agents.
The synthesis of a novel series of 4-thiazolylpyrazolyl derivatives is described in the present report. All the newly synthesized compounds were examined for their anti-inflammatory activity using cotton pellet-induced granuloma and carrageenan-induced rat paw edema bioassays. Their inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), ulcerogenic effect and acute toxicity were also determined. Furthermore, all compounds were evaluated for their in vitro antimicrobial activity against Escherichia coli, Staphylococcus aureus and Candida albicans. A docking pose for compounds 8b, 10a and 10b separately in the active site of the human COX-2 enzyme and DNA-gyrase B was also obtained. The results revealed that compounds 8b, 10a and 10b exhibited good anti-inflammatory activity with no or minimal ulcerogenic effect and good safety margin. Compounds 10a and 10b were found to be the most potent anti-inflammatory agents in the present study. Meanwhile, 10a and 10b displayed higher selective inhibitory activity towards COX-2 compared to indomethacin. Moreover, compounds 10a and 10b exhibited promising antibacterial against both E. coli and S. aureus. Docking studies for 8b, 10a and 10b with COX-2 (PDB ID: 1CX2) and DNA-gyrase B (PDB ID: 1EI1) showed good binding profile.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt. adnbekhit@hotmail.com
Adnan A
AA
Bekhit
Hesham T Y
HT
Fahmy
Sherif A F
SA
Rostom
Alaa
A
El-Din A Bekhit
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D002351:Carrageenan; D020134:Catalytic Domain; D032561:Cotton Fiber; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004926:Escherichia coli / Q000187:drug effects*; D006099:Granuloma / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013211:Staphylococcus aureus / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D011720:Pyrazoles; D013844:Thiazoles; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2