Synthesis of novel 2-mercaptobenzoxazole based 1,2,3-triazoles as inhibitors of proinflammatory cytokines and suppressors of COX-2 gene expression.
A library of novel bis-heterocycles containing 2-mercaptobenzoxazole based 1,2,3-triazoles has been synthesized using click chemistry approach. The compound 4 exhibited the most potent in vivo anti-inflammatory activity with 66.66% and 61.11% inhibition in comparison to celecoxib which showed 72.22% and 65.55% inhibition after 3 h and 5 h respectively. The compounds 4 and 9 suppressed the COX-2 gene expression by 0.94 and 0.79 fold and exhibited a selective index (COX-1/COX-2) of 64.79 and 66.47 respectively in comparison to celecoxib (SI value of 75.56). The in silico molecular docking studies showed the interactions of these molecules with Tyr-59, Tyr-119 and Gly-121. When compared with the standard drug celecoxib, compounds 4, 5, 7, 9 and 16 did not cause any gastric ulceration.
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Saqlain
S
Haider
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India. Electronic address: msalam@jamiahamdard.ac.in.
Mohammad Sarwar
MS
Alam
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Hinna
H
Hamid
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Syed
S
Shafi
Unit for Research and Development of Information Products - CSIR, Pune 411038, India.
Abhijeet
A
Dhulap
Department of Chemistry, Faculty of Science, University of Delhi, New Delhi 110007, India.
Firasat
F
Hussain
Functional Genomics Unit, CSIR - Institute of Genomics & Integrative Biology, New Delhi 110007, India.
Perwez
P
Alam
Department of Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University) New Delhi 110 062, India.
Sadiq
S
Umar
Functional Genomics Unit, CSIR - Institute of Genomics & Integrative Biology, New Delhi 110007, India.
M A Q
MA
Pasha
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Sameena
S
Bano
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Syed
S
Nazreen
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Yakub
Y
Ali
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Chetna
C
Kharbanda
D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D001583:Benzoxazoles / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D008958:Models, Molecular; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014230:Triazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001583:Benzoxazoles; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D013438:Sulfhydryl Compounds; D014230:Triazoles; C525534:2-mercaptobenzoxazole; D051546:Cyclooxygenase 2
Antinociceptive; Crystallography; Cyclooxygenase; Gene expression; Molecular docking