Arginase Flavonoid Anti-Leishmanial in Silico Inhibitors Flagged against Anti-Targets

• Published in: Molecules (Basel, Switzerland) Vol. 21; no. 5; p. 589
• Main Authors: Glisic, Sanja, Sencanski, Milan, Perovic, Vladimir, Stevanovic, Strahinja, García-Sosa, Alfonso T
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.05.2016; MDPI
• Subjects: anti-target; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; arginase; Arginase - antagonists & inhibitors; Bacterial infections; Biosynthesis; Computer Simulation; cytochrome P450; Databases, Chemical; Drug resistance; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Enzymes; flavonoid; Flavonoids; Flavonoids - chemistry; Flavonoids - pharmacology; Humans; in silico; Infections; Infectious diseases; Leishmania; Leishmania - enzymology; Leishmania - pathogenicity; leishmaniasis; Metabolism; Molecular Structure; Natural products; Parasites; Parasitic diseases; Polyamines; pregnane-X-receptor; Protozoa; Protozoan Proteins - antagonists & inhibitors; Quantitative Structure-Activity Relationship; screen; sulfotransferase; Toxicity; Tropical diseases; natural products; pregnane-X-receptor; Leishmania; anti-target; screen; cytochrome P450; flavonoid; in silico; sulfotransferase; leishmaniasis; arginase
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules21050589

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.