In vivo anti-inflammatory activity and docking study of newly synthesized benzimidazole derivatives bearing oxadiazole and morpholine rings

Ankita Rathore; Raja Sudhakar; Mohamed Jawed Ahsan; Abuzer Ali; Naidu Subbarao; Surender Singh Jadav; Sadiq Umar; M Shahar Yar

doi:10.1016/j.bioorg.2016.11.014

In vivo anti-inflammatory activity and docking study of newly synthesized benzimidazole derivatives bearing oxadiazole and morpholine rings

Bioorg Chem. 2017 Feb:70:107-117. doi: 10.1016/j.bioorg.2016.11.014. Epub 2016 Nov 29.

Authors

Ankita Rathore¹, Raja Sudhakar², Mohamed Jawed Ahsan³, Abuzer Ali⁴, Naidu Subbarao², Surender Singh Jadav⁵, Sadiq Umar⁶, M Shahar Yar⁷

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India; College of Pharmacy and Dentistry, Buraydah Private Colleges, Al-Qassim 31717, Saudi Arabia.
² School of Computational & Integrative Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
³ Department of Medicinal Chemistry, Maharishi Arvind College of Pharmacy Jaipur, Rajasthan 301 039, India.
⁴ College of Clinical Pharmacy, University of Dammam, Dammam 31441, Saudi Arabia.
⁵ Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835 215, India.
⁶ Department of Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
⁷ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India. Electronic address: yarmsy@rediffmail.com.

PMID: 27923497
DOI: 10.1016/j.bioorg.2016.11.014

Abstract

In search of potential therapeutics for inflammatory disease, we report herein the synthesis, characterization and anti-inflammatory activities of a new series of 1-{(5-substituted-1,3,4-oxadiazol-2-yl)methyl}-2-(morpholinomethyl)-1H-benzimidazoles (5a-r). The anti-inflammatory activity of the compounds was evaluated using carrageenan induced rat paw edema test. Some compounds showed excellent anti-inflammatory activity in carrageenan induced rat paw edema test. 1-{(5-(2-Chlorophenyl)-1,3,4-oxadiazol-2-yl)methyl}-2-(morpholinomethyl)-1H-benzimidazole (5g) showed maximum anti-inflammatory (74.17±1.28% inhibition) with reduced ulcerogenic and lipid peroxidation profile and also showed significant COX-2 inhibition with IC₅₀ values of 8.00μM. Compounds 5o and 5q were also found to exhibit good COX-2 inhibition with IC₅₀ values of 11.4 and 13.7μM concentrations. Molecular docking study showed that morpholine and oxadiazole rings linked to the benzimidazole nucleus play an important role in binding with the COX-2.

Keywords: Anti-inflammatory; Benzimidazole; Lipid peroxidation; Molecular docking; Oxadiazole; Ulcerogenic activity.

Publication types

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

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / adverse effects
Anti-Inflammatory Agents, Non-Steroidal / chemistry*
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
Benzimidazoles / adverse effects
Benzimidazoles / chemistry*
Benzimidazoles / pharmacology
Benzimidazoles / therapeutic use*
Cyclooxygenase 2 Inhibitors / adverse effects
Cyclooxygenase 2 Inhibitors / chemistry
Cyclooxygenase 2 Inhibitors / pharmacology
Cyclooxygenase 2 Inhibitors / therapeutic use
Edema / drug therapy
Male
Models, Molecular
Molecular Docking Simulation
Oxadiazoles / adverse effects
Oxadiazoles / chemistry*
Oxadiazoles / pharmacology
Oxadiazoles / therapeutic use*
Rats, Wistar
Ulcer / chemically induced

Substances

Anti-Inflammatory Agents, Non-Steroidal
Benzimidazoles
Cyclooxygenase 2 Inhibitors
Oxadiazoles