VIRTUAL SCREENING OF PHYTOCHEMICALS FOR METHOTREXATE LIKE DIHYDROFOLATE REDUCTASE AND AMINOIMIDAZOLE-4-CARBOXAMIDE RIBONUCLEOTIDE (AICAR) TRANSFORMYLASE INHIBITORY PROPERTY USING MOLEGRO VIRTUAL DOCKER

Abstract

Objective: Methotrexate is an effective treatment for autoimmune diseases like Rheumatoid arthritis, vasculitis, and Psoriasis. Our aim is to do in silico screening of various phytochemicals present in common medicinal plants used in India for arthritis and fever for possible Dihydrofolate reductase (DHFR) and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) Transformylase inhibitory property similar to methotrexate (MTX) using molecular docking method.Methods: We did docking of 142 phytochemicals against DHFR and AICAR Transformylase domain of ATIC (AICAR Transformylase/Inosine monophosphate cyclohydrolase) enzyme structures extracted from Protein Data Bank (4M6K, 1P4R respectively), by utilizing the Molegro virtual docker Software. The docking scores of phytochemicals were compared with the scores of respective native reference ligands present in the crystal structures.Results: Compounds, dicrocin, melianone, calotropin, uscharidin and mauritine A showed more negative moldoc and rerank scores compared to folic acid and MTX when docked in the folate-binding pocket of DHFR. Dicrocin, melianone and hecogenin showed more negative moldoc and rerank scores compared to scores of AICAR and MTX, when docked in the cavity in AICAR Transformylase, which binds AICAR.Conclusion: The protein-ligand interaction plays a significant role in structural based drug designing. The present analysis shows that Melianone and dicrocin could be the potential lead molecules for the inhibition of both DHFR and AICAR transformylase like MTX. Uscharidin, calotropin, and mauritine A may be the potential DHFR inhibitor lead molecules and Hecogenin could be the potential lead molecule for inhibition of AICAR transformylase.Keywords: Dihydrofolate reductase, AICAR Transformylase, Melianone, Hecogenin, Mauritine