Mefenamic acid inhibit transforming growth factor-beta type-1: Repurposing anti-inflammatory drugs in wound healing using in-silico approaches

Abstract

Mefenamic acid inhibit transforming growth factor-beta type-1: Repurposing anti-inflammatory drugs in wound healing using in-silico approaches Miah Roney a,b, Abdul Rashid Issahaku c,d, Normaiza Binti Zamri a, Mohd Fadhlizil Fasihi Mohd Aluwi a,b,* a Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Tun Razak, 26300 Gambang, Kuantan, Pahang Darul Makmur, Malaysia b Centre for Bio-Aromatic Research, Universiti Malaysia Pahang Al-Sultan Abdulah, Lebuhraya Tun Razak, 26300 Gambang, Kuantan, Pahang Darul Makmur, Malaysia c Department of Chemistry, University of the Free State, 205 Nelson Mandela Avenue, Bloemfontein 9301, South Africa d West African Centre for Computational Research and Innovation, Ghana A R T I C L E I N F O Handling Editor: Prof A Angelo Azzi Keywords: Mefenamic acid In-silico Wound healing Docking MD simulation A B S T R A C T Due to low cost and time-saving benefits, drug repurposing is a safe and successful method to discover drug. A druggable target for inflammation, transforming growth factor-beta type-1 (TGF-β 1) has been identified to be associated with wound healing. Finding the most effective TGF-β 1 inhibitor among FDA-approved anti-inflammatory medications was the goal of the current investigation. To find the best hits against TGF-β 1, we used structure-based virtual screening on medications that have received FDA approval. We discovered two FDAapproved medications with notable selectivity and affinity for the binding pocket of TGF-β 1. Mefenamic acid, one of these found hits, interacts with key TGF-β 1 residues and favourably attaches to the binding pocket, requiring further study. The kinetics of the binding between mefenamic acid and TGF-β 1 were revealed by allatom precise molecular dynamics (MD) simulations. Mefenamic acid, which may also be used as a possible lead chemical against TGF-β 1, may be a promising TGF-β 1 inhibitor.