Psoriasis is characterized as chronic inflammatory disorder of skin having unregulated hyperproliferation and shedding of plaques. As per first line treatment
methotrexate is the most widely used cytotoxic
drug for
psoriasis. It shows anti-proliferative effect with hDHFR while anti-inflammatory and immunosuppressive action is due to AICART. Serious hepatotoxic effects are recognized with long-term treatment of
methotrexate. In this study, in silico technique is used in this work to find Dual-Acting
Methotrexate-like molecules with increased efficacy and decreased toxicity. Structure-based virtual screening assisted by a fragment-based method against a library of chemicals that are similar to
methotrexate revealing 36 and 27 potential inhibitors of hDHFR and AICART respectively. Further, based on dock score, binding energy, molecular interactions, and ADME/T analysis compound 135565151 was chosen for dynamic stability evaluation. Overall, these findings provided information on possible
methotrexate analogues for the treatment of
psoriasis that had lower hepatotoxicity.Communicated by Ramaswamy H. Sarma.