title: Arginase Flavonoid Anti-Leishmanial in Silico Inhibitors Flagged against Anti-Targets.
abstract: Arginase, a drug target for the treatment of leishmaniasis, is involved in the biosynthesis of polyamines. Flavonoids are interesting natural compounds found in many foods and some of them may inhibit this enzyme. The MetIDB database containing 5667 compounds was screened using an EIIP/AQVN filter and 3D QSAR to find the most promising candidate compounds. In addition, these top hits were screened in silico versus human arginase and an anti-target battery consisting of cytochromes P450 2a6, 2c9, 3a4, sulfotransferase, and the pregnane-X-receptor in order to flag their possible interactions with these proteins involved in the metabolism of substances. The resulting compounds may have promise to be further developed for the treatment of leishmaniasis.
authors.affiliation: Center for Multidisciplinary Research, Institute of Nuclear Sciences VINCA, University of Belgrade, P.O. Box 522, 11001 Belgrade, Serbia. sanja@vin.bg.ac.rs.
authors.forename: Sanja
authors.initials: S
authors.lastname: Glisic
authors.affiliation: Center for Multidisciplinary Research, Institute of Nuclear Sciences VINCA, University of Belgrade, P.O. Box 522, 11001 Belgrade, Serbia. sencanski@vin.bg.ac.rs.
authors.forename: Milan
authors.initials: M
authors.lastname: Sencanski
authors.affiliation: Center for Multidisciplinary Research, Institute of Nuclear Sciences VINCA, University of Belgrade, P.O. Box 522, 11001 Belgrade, Serbia. vladaper@vinca.rs.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Perovic
authors.affiliation: Center for Multidisciplinary Research, Institute of Nuclear Sciences VINCA, University of Belgrade, P.O. Box 522, 11001 Belgrade, Serbia. strahinja.stevanovic@protonmail.com.
authors.forename: Strahinja
authors.initials: S
authors.lastname: Stevanovic
authors.affiliation: Institute of Chemistry, University of Tartu, Ravila 14a, Tartu 50411, Estonia. alfonsog@ut.ee.
authors.forename: Alfonso T
authors.initials: AT
authors.lastname: García-Sosa
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology; D001119:Arginase / Q000037:antagonists & inhibitors*; D003198:Computer Simulation; D062126:Databases, Chemical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007891:Leishmania / Q000201:enzymology / Q000472:pathogenicity; D015394:Molecular Structure; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids; D015800:Protozoan Proteins; D001119:Arginase
keywords: Leishmania; anti-target; arginase; cytochrome P450; flavonoid; in silico; leishmaniasis; natural products; pregnane-X-receptor; screen; sulfotransferase