title: In-silico analyses of natural products on leishmania enzyme targets.
abstract: Natural products are compounds that are isolated from plants, provide a variety of lead structures for the development of new drugs by the pharmaceutical industry. The interest in these substances increases because of their beneficial effects on human health, which include antiviral, antiallergic, antiplatelet, anti-inflammatory, antitumor, antioxidant, and antiparasitic activities. Leishmaniasis is the infection caused by protozoa of the genus Leishmania, which affects mainly people who live in poor countries, and can cause chronic fever, liver problems, anemia, and other blood problems. Current chemotherapies against the disease cause side effects, and are ineffective. There are no vaccines, and new chemotherapeutic agents for the treatment of leishmaniasis are greatly needed. This work reports on some of the enzymatic targets studied in the development of new drugs using natural products as inhibitors for the treatment of leishmaniasis. We applied ligand-based-virtual screening using Random Forest, associated with structure-based-virtual screening (docking), of a small dataset of 683 flavonoids and derivatives from an in-house data bank to select structures with potential inhibitory activity against pyruvate kinase, an important enzyme in Leishmania mexicana's energy production chemistry. The computer-aided drug design studies revealed good results against Leishmaniasis for flavones.
authors.forename: L
authors.initials: L
authors.lastname: Scotti
authors.forename: H
authors.initials: H
authors.lastname: Ishiki
authors.forename: F J B
authors.initials: FJ
authors.lastname: Mendonça Júnior
authors.forename: M S
authors.initials: MS
authors.lastname: Da Silva
authors.affiliation: Health Sciences Center, Federal University of Paraiba, Campus I, 58051-970, Joao Pessoa, PB, Brazil. luciana.scotti@gmail.com.
authors.forename: M T
authors.initials: MT
authors.lastname: Scotti
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000228:Adenine Phosphoribosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019540:Area Under Curve; D001119:Arginase / Q000037:antagonists & inhibitors / Q000378:metabolism; D001665:Binding Sites; D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017076:Computer-Aided Design; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007891:Leishmania / Q000187:drug effects / Q000201:enzymology*; D062105:Molecular Docking Simulation; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012372:ROC Curve
chemical_list: D001688:Biological Products; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; D010088:Oxidoreductases; C085592:pteridine reductase; D044925:Oxidoreductases Acting on CH-CH Group Donors; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase; D000228:Adenine Phosphoribosyltransferase; D001119:Arginase; D019696:Peptidylprolyl Isomerase