VIRTUAL SCREENING OF PHYTOCHEMICALS OF MORINDA CITRIFOLIA AS ANTI-INFLAMMATORY AND ANTI-ALZHEIMER AGENTS USING MOLEGRO VIRTUAL DOCKER ON p38-α MITOGEN ACTIVATED PROTEIN KINASE ENZYME

Objective: Pharmacological and genetic inhibition of p38α mitogen-activated protein kinase (p38α MAPK) has potential in the treatment of humandiseases such as autoimmune diseases, heart failure, Alzheimer disease, and Parkinsonism. Our aim is to do in-silico screening of phytochemicals ofMorinda citrifolia for p38α MAPK inhibitory property by docking method.Methods: We did docking of various phytochemicals present in M. citrifolia against p38α MAPK enzyme extracted from Protein Data Bank (ID-4F9Y),by utilizing the Molegro virtual docker Software. The docking scores of phytochemicals were compared with the scores of native reference ligandspresent in the crystal structure 4F9Y.Results: Isoprincepin and balanophonin show better docking scores when compared to reference ligands in the protein. Isoprincepin has potentialto act in a highly selective manner on p38α MAPK as it binds to Met 109 in the phylogenetically conserved kinase hinge region and thereby induces aconformational change known as glycine flip phenomenon. Balanophonin has favorable physiochemical properties for blood-brain barrier penetrationand can act on p38α MAPK in the brain.Conclusion: Some of the phytochemicals present in M. citrifolia have p38α MAPK binding and possible inhibitory potential.Keywords: p38α mitogen-activated protein kinase, Isoprincepin, Balanophonin, Molegro virtual docker

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

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