title: Repositioning of 2,4-dichlorophenoxy acetic acid as a potential anti-inflammatory agent: in silico and pharmaceutical formulation study.
abstract: 2,4-Dichlorophenoxy acetic acid (2,4-D) is a well-known plant auxin which is widely used in plant tissue culture experiments as well as a weed killer and a herbicide. In this study, 2,4-D was rediscovered as a new anti-inflammatory agent through an in silico molecular modeling and docking studies along with drug formulation and in vivo anti-inflammatory inspection. The molecular modeling and docking studies indicated high affinity of 2,4-D toward COX-2 enzyme in a way similar to Ibuprofen, suggesting a higher anti-inflammatory activity. Molecular docking by both MOE 2013.08 and Leadit 2.1.2 revealed excellent binding pattern compared to some of well-known non-steroidal anti-inflammatory drugs. 2,4-D was formulated in different gel bases. In vitro drug release experiments were used to examine the best 2,4-D formula for in vivo studies. In vivo carrageenan-induced hind paw edema inflammatory model in rats was used to test the in silico finding. 2,4-D showed potential in vivo anti-inflammatory activity and significantly reduced the concentration of prostaglandin E2 in hind paw tissues in a way similar to Ibuprofen. These results may open the door to introduce a new anti-inflammatory molecule; especially that 2,4-D is a well-investigated regarding its toxicity and side effect.
authors.affiliation: College of Clinical Pharmacy, King Faisal University, P.O. 380, Ahsaa 31982, Saudi Arabia; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, EinHelwan, Cairo, 11795, Egypt. Electronic address: mmohammed@kfu.edu.sa.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Khedr
authors.affiliation: College of Clinical Pharmacy, King Faisal University, P.O. 380, Ahsaa 31982, Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, University of Zagazig, Zagazig 44519, Egypt.
authors.forename: Tamer M
authors.initials: TM
authors.lastname: Shehata
authors.affiliation: College of Clinical Pharmacy, King Faisal University, P.O. 380, Ahsaa 31982, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, University of Zagazig, Zagazig 44519, Egypt.
authors.forename: Maged E
authors.initials: ME
authors.lastname: Mohamed
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D058492:Drug Repositioning / Q000379:methods; D004487:Edema / Q000188:drug therapy / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D015084:2,4-Dichlorophenoxyacetic Acid; D002351:Carrageenan; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: 2,4-Dichlorophenoxy acetic acid (PubChem CID: 1486); 2.4-Dichlorophenoxy acetic acid; Alcofenac (PubChem CID: 602242); Desmethyl fluriprofen (PubChem CID: 11831237); Fluriprofen (PubChem CID: 3394); Gel formulation; Ibuprofen (PubChem CID: 3672); Indomethacin (PubChem CID: 3715); Ketoprofen (PubChem CID: 3825); Molecular docking; Molecular modeling; Naproxen (PubChem CID: 156391); Propylene glycol (PubChem CID: 1030); Prostaglandin E(2); Rat hind paw; and Carboxymethyl cellulose (PubChem CID: 23706213)