title: In vivo anti-inflammatory activity and docking study of newly synthesized benzimidazole derivatives bearing oxadiazole and morpholine rings.
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 IC50values of 8.00μM. Compounds 5o and 5q were also found to exhibit good COX-2 inhibition with IC50values 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.
authors.affiliation: 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.
authors.forename: Ankita
authors.initials: A
authors.lastname: Rathore
authors.affiliation: School of Computational & Integrative Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Raja
authors.initials: R
authors.lastname: Sudhakar
authors.affiliation: Department of Medicinal Chemistry, Maharishi Arvind College of Pharmacy Jaipur, Rajasthan 301 039, India.
authors.forename: Mohamed Jawed
authors.initials: MJ
authors.lastname: Ahsan
authors.affiliation: College of Clinical Pharmacy, University of Dammam, Dammam 31441, Saudi Arabia.
authors.forename: Abuzer
authors.initials: A
authors.lastname: Ali
authors.affiliation: School of Computational & Integrative Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Naidu
authors.initials: N
authors.lastname: Subbarao
authors.affiliation: Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835 215, India.
authors.forename: Surender Singh
authors.initials: SS
authors.lastname: Jadav
authors.affiliation: Department of Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Sadiq
authors.initials: S
authors.lastname: Umar
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India. Electronic address: yarmsy@rediffmail.com.
authors.forename: M Shahar
authors.initials: MS
authors.lastname: Yar
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy; D008297:Male; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D010069:Oxadiazoles / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D014456:Ulcer / Q000139:chemically induced
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001562:Benzimidazoles; D052246:Cyclooxygenase 2 Inhibitors; D010069:Oxadiazoles
keywords: Anti-inflammatory; Benzimidazole; Lipid peroxidation; Molecular docking; Oxadiazole; Ulcerogenic activity