title: In-silico screening of Schistosoma mansoni Sirtuin1 inhibitors for prioritization of drug candidates.
abstract: Schistosomiasis is a common, neglected parasitic disease caused by Schistosoma mansoni. Availability of two specific drug oxamniquine and praziquintel for treatment of the disease is a major concern. Recently NAD+ dependent lysine deacetylases have been identified as new drug targets in pathogens. Sirtuins are NAD+ dependent lysine deacetylases that are involved in a wide variety of vital cellular processes. Amongst them, members of sirtuin's class1 proteins are considered to be main target of the drugs. Sirtinol and Salermide are two known inhibitors of Schistosoma mansoni Class1sirtuin which is a protein with unknown 3-D structure. Here, we investigate molecular insights of interaction between modeled sirtuin1 structure and it's inhibitors, that were derivatives of Sirtinol and Salermide, to prioritize them for their binding affinities with target. A detailed examination of absorption, distribution, metabolism and toxicity of these inhibitors has also been included in the study. Finally we found two derivatives of Sirtinol to be most appropriate drug candidates for Schistosomiasis.
authors.affiliation: Institute of Interdisciplinary Studies, Center of Bioinformatics, Nehru Science Center, University of Allahabad, Allahabad, 211002 India.
authors.forename: Raghvendra
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Biotechnology, Motilal Nehru National Institute of Technology Allahabad, Allahabad, 211004 India.
authors.forename: Birendra Singh
authors.initials: BS
authors.lastname: Yadav
authors.affiliation: Institute of Interdisciplinary Studies, Center of Bioinformatics, Nehru Science Center, University of Allahabad, Allahabad, 211002 India.
authors.forename: Swati
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Mathematics, University of Allahabad, Allahabad, 211002 India.
authors.forename: Paras Nath
authors.initials: PN
authors.lastname: Pandey
authors.affiliation: Department of Biotechnology, Motilal Nehru National Institute of Technology Allahabad, Allahabad, 211004 India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Mani
keywords: ADMET profiling; Intestinal schistosomiasis; Molecular docking; Sirtinol 1; Sirtuin 1