Synthesis of novel 1,2,3-triazole based benzoxazolinones: their TNF-α based molecular docking with in-vivo anti-inflammatory, antinociceptive activities and ulcerogenic risk evaluation

Saqlain Haider; M Sarwar Alam; Hinna Hamid; Syed Shafi; Amit Nargotra; Priya Mahajan; Syed Nazreen; Arunasree M Kalle; Chetna Kharbanda; Yakub Ali; Aftab Alam; Amulya K Panda

doi:10.1016/j.ejmech.2013.10.032

Synthesis of novel 1,2,3-triazole based benzoxazolinones: their TNF-α based molecular docking with in-vivo anti-inflammatory, antinociceptive activities and ulcerogenic risk evaluation

Eur J Med Chem. 2013:70:579-88. doi: 10.1016/j.ejmech.2013.10.032. Epub 2013 Oct 22.

Authors

Saqlain Haider¹, M Sarwar Alam, Hinna Hamid, Syed Shafi, Amit Nargotra, Priya Mahajan, Syed Nazreen, Arunasree M Kalle, Chetna Kharbanda, Yakub Ali, Aftab Alam, Amulya K Panda

Affiliation

¹ Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.

PMID: 24211633
DOI: 10.1016/j.ejmech.2013.10.032

Abstract

A library of novel bis-heterocycles containing benzoxazolinone based 1,2,3-triazoles has been synthesized using click chemistry approach. The compound 3f exhibited potent selective COX-2 inhibition of 59.48% in comparison to standard drug celecoxib (66.36% inhibition). The compound 3i showed significant (p < 0.001, 50.95%), TNF-α inhibitory activity as compared to indomethacin (p < 0.001, 64.01%). The results of the carrageenan induced hind paw oedema showed that compounds 3a, 3f, 3i, 3o, and 3e exhibited potent anti-inflammatory activity in comparison to Indomethacin. The molecular docking studies revealed that 3i exhibits strong inhibitory effect due to the extra stability of the complex because of an extra π-π bond. The histopathology report showed that none of the compounds caused gastric ulceration.

Keywords: 1,2,3-Triazole; Benzoxazolinone; Carrageenan cyclooxygenase; Click chemistry; Molecular docking.

Publication types

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

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Benzoxazoles / administration & dosage
Benzoxazoles / chemical synthesis
Benzoxazoles / pharmacology*
Carrageenan
Cyclooxygenase 2 / metabolism
Cyclooxygenase 2 Inhibitors / administration & dosage
Cyclooxygenase 2 Inhibitors / chemical synthesis
Cyclooxygenase 2 Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Edema / chemically induced
Edema / drug therapy*
Epithelial Cells / cytology
Gastric Mucosa / cytology
Humans
Models, Molecular
Molecular Structure
Rats
Risk Factors
Structure-Activity Relationship
Triazoles / chemistry*
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Tumor Necrosis Factor-alpha / metabolism

Substances

Anti-Inflammatory Agents, Non-Steroidal
Benzoxazoles
Cyclooxygenase 2 Inhibitors
Triazoles
Tumor Necrosis Factor-alpha
Carrageenan
Cyclooxygenase 2