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Biginelli reaction (synthesis and chemoenzymatic resolution) and biotransformation of steroids by microorganisms

Grant number: 19/07654-2
Support Opportunities:Regular Research Grants
Start date: September 01, 2019
End date: November 30, 2021
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal Investigator:Andre Luiz Meleiro Porto
Grantee:Andre Luiz Meleiro Porto
Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Part I of this Regular Research Grant project will study a class of compounds called dihydropyrimidinones (DHPMs), which are known to have a variety of biological properties. Thus, synthetic methodologies will be developed with the purpose of obtaining numerous racemic DHPMs, most of them unpublished in the literature. These compounds will undergo biological assays concerning the negligible diseases caused by protozoa such as leishmaniasis and Chagas diseases. As well, the potential of these compounds will be evaluated against tumor cells and immunomodulatory properties. Also racemic DHPMs containing the tetrazole nucleus will be synthesized, which is known to have relevant biological properties. The racemic DHPMs will be submitted to the enzymatic kinetic resolution, which will be performed after a screening process involving the use of commercial enzymes, in order to perform the separation of the enantiomers. The enantiomerically pure compounds will be evaluated in the same biological assays. In Part II the biotransformation reactions of steroids by marine environment fungi will be investigated, mainly in electrons not activated electrons. Isolation and identification of the main biotransformation products of the 17±-ethynylestradiol steroids, nandrolone decanoate, among others, will be performed and analytical techniques (LC-UV, LC-MS, GC-MS, NMR) will be used. The contribution of this project is important for the areas of organic chemistry, biocatalysis, pharmaceutical, environmental, as well as for the training of qualified human resources in the area of biotechnology, through the use of biological agents for the production of bioactive compounds. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications (8)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CARDOSO DE PAULA, SAMUEL FILIPE; ROSSET, ISAC GEORGE; MELEIRO PORTO, ANDRE LUIZ. Hydroxylated steroids in C-7 and C-15 positions from progesterone bio-oxidation by the marine-derived fungus Penicillium oxalicum CBMAI 1996. BIOCATALYSIS AND AGRICULTURAL BIOTECHNOLOGY, v. 37, . (19/07654-2, 16/20155-7)
ZANIN, LUCAS LIMA; BRITO MATOS, THIAGO KELVIN; LEITAO, ANDREI; ELLENA, JAVIER; MELEIRO PORTO, ANDRE LUIZ. Biocatalytic Kinetic Resolution to Access Enantiomerically Enriched Dihydropyrimidinone/Thiones through Recognition of a Remote Stereocentre. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, v. N/A, p. 9-pg., . (19/07654-2, 18/15904-6, 16/20155-7, 17/15850-0)
DE QUEIROZ, THAYANE MELO; ELLENA, JAVIER; PORTO, ANDRE L. M.. Biotransformation of Ethinylestradiol by Whole Cells of Brazilian Marine-Derived FungusPenicillium oxalicumCBMAI 1996. MARINE BIOTECHNOLOGY, v. 22, n. 5, p. 10-pg., . (19/07654-2, 16/20155-7)
FERREIRA, IRLON M.; JIMENEZ, DAVID E. Q.; LOPES, SAMUEL Q.; DE OLIVEIRA, ALEX DE NAZARE; MATOS, MATEUS J. S.; PORTO, ANDRE L. M.. Ene-reductases: Contribution from Brazilian fungi in organic synthesis. RESULTS IN CHEMISTRY, v. 5, p. 12-pg., . (18/15904-6, 19/07654-2, 16/20155-7)
FÁBIO R. RIGOLIN; CARLA A. LEITE; WILLIAN G. BIROLLI; ANDRÉ L. M. PORTO; MIRNA H. R. SELEGHIM. Biodegradation of the Pyrethroid Pesticide Gamma-Cyhalothrin by Fungi from a Brazilian Cave. Journal of the Brazilian Chemical Society, v. 35, n. 8, . (18/15904-6, 17/19721-0, 16/20155-7, 19/07654-2)
DE QUEIROZ, THAYANE MELO; ELLENA, JAVIER; PORTO, ANDRE L. M.. Biotransformation of Ethinylestradiol by Whole Cells of Brazilian Marine-Derived FungusPenicillium oxalicumCBMAI 1996. MARINE BIOTECHNOLOGY, . (19/07654-2, 16/20155-7)
GARCIA, ANUSKA C. F. S.; BIROLLI, WILLIAN G.; ARAUJO, BRUNO R.; MARQUES, CARLA G.; BARBOSA-JUNIOR, ANTONIO M.; DINIZ, LEANDRO E. C.; PORTO, ANDRE L. M.; ROMAO, LUCIANE P. C.. Biodegradation of the Polycyclic Aromatic Hydrocarbon Fluoranthene by Fungi Strains from a Brazilian Tropical Peat. Journal of the Brazilian Chemical Society, v. 32, n. 9, p. 1874-1883, . (16/20155-7, 19/07654-2, 17/19721-0)