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.

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).