Synthesis of novel 2-mercaptobenzoxazole based 1,2,3-triazoles as inhibitors of proinflammatory cytokines and suppressors of COX-2 gene expression

Saqlain Haider; Mohammad Sarwar Alam; Hinna Hamid; Syed Shafi; Abhijeet Dhulap; Firasat Hussain; Perwez Alam; Sadiq Umar; M A Q Pasha; Sameena Bano; Syed Nazreen; Yakub Ali; Chetna Kharbanda

doi:10.1016/j.ejmech.2014.05.012

Synthesis of novel 2-mercaptobenzoxazole based 1,2,3-triazoles as inhibitors of proinflammatory cytokines and suppressors of COX-2 gene expression

Eur J Med Chem. 2014 Jun 23:81:204-17. doi: 10.1016/j.ejmech.2014.05.012. Epub 2014 May 4.

Authors

Affiliations

¹ Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
² Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India. Electronic address: msalam@jamiahamdard.ac.in.
³ Unit for Research and Development of Information Products - CSIR, Pune 411038, India.
⁴ Department of Chemistry, Faculty of Science, University of Delhi, New Delhi 110007, India.
⁵ Functional Genomics Unit, CSIR - Institute of Genomics & Integrative Biology, New Delhi 110007, India.
⁶ Department of Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University) New Delhi 110 062, India.

PMID: 24836072
DOI: 10.1016/j.ejmech.2014.05.012

Abstract

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.

Keywords: Antinociceptive; Crystallography; Cyclooxygenase; Gene expression; Molecular docking.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analgesics / administration & dosage
Analgesics / chemical synthesis
Analgesics / pharmacology*
Animals
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Benzoxazoles / chemistry*
Cyclooxygenase 2 / biosynthesis
Cyclooxygenase 2 / genetics*
Cyclooxygenase 2 Inhibitors / administration & dosage
Cyclooxygenase 2 Inhibitors / chemical synthesis
Cyclooxygenase 2 Inhibitors / pharmacology*
Cytokines / antagonists & inhibitors*
Cytokines / blood
Cytokines / immunology
Edema / chemically induced
Edema / drug therapy
Gene Expression Regulation, Enzymologic / drug effects*
HeLa Cells
Humans
Inflammation / drug therapy
Mice
Models, Molecular
Pain / chemically induced
Pain / drug therapy
Rats
Rats, Wistar
Sulfhydryl Compounds / chemistry*
Triazoles / administration & dosage
Triazoles / chemical synthesis
Triazoles / pharmacology*
Tumor Cells, Cultured

Substances

Analgesics
Anti-Inflammatory Agents, Non-Steroidal
Benzoxazoles
Cyclooxygenase 2 Inhibitors
Cytokines
Sulfhydryl Compounds
Triazoles
2-mercaptobenzoxazole
Cyclooxygenase 2