Banca de DEFESA: LEONARDO ARAUJO SILVA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : LEONARDO ARAUJO SILVA
DATE: 08/08/2022
TIME: 13:00
LOCAL: Apresentação em ambiente virtual, via Google Meet
TITLE:

Synthesis and evaluation of the trypanocidal activity of new beta-lapachone-derived azoles

KEY WORDS:

beta-lapachone, naftoimidazoles, naftoxazole, synthesis, Trypanosoma cruzi

PAGES: 268
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Síntese Orgânica
SUMMARY:

More than 100 years after its discovery, Chagas disease still represents a challenge for humanity, since its treatment has serious gaps. In addition to not being satisfactorily effective in the chronic phase of the disease, the drugs used worldwide for its treatment, nifurtimox and benznidazole, cause severe side effects to patients treated with them. Thousands of people die each year due to this disease, which mainly affects tropical regions, such as Brazil. In Brazil, only benznidazole is authorized by the National Health Surveillance Agency (ANVISA) for the treatment of Chagas disease. Thus, it is essential that the scientific community dedicate itself to the search for new drugs for the treatment of Chagas disease, more efficient than the actual. In this sense, beta-lapachone derivatives have emerged as promising compounds, especially the azole derivatives. beta-lapachone is a naphthoquinone, found in several tree and shrub species of the Bignoniaceae family, among them, the ipê. In the last decades, several research groups, especially in Brazil, have been dedicated to the synthesis of beta-lapachone derivatives, to combat several pathogens, including Trypanosoma cruzi, which causes Chagas disease. In this work, 26 imidazole derivatives and 2 oxazole derivatives of beta-lapachone were synthesized, of which 21 are unpublished, in addition, a 2-amine-oxazole derived from ortho-phenanthroline-quinone was synthesized. Among the synthesized compounds, 16 were evaluated in vitro for trypanocidal activity, in addition to beta-lapachone, against the amastigote and trypomastigote forms of T. cruzi. Nine of the evaluated compounds were more active in the tests than beta- lapachone, under the conditions tested, among which, two were more active than the standard drug itself, benznidazole. It was also possible to verify that both present greater selectivity for the parasite than for the host cells. One of these two most active had its mechanism of action under the parasite investigated, and it was found that the main damage caused by the compound in question was in the mitochondria, causing swelling, and a washing aspect, in the organelle. In addition to the valuable results of trypanocidal activity, this work also enabled the development of a new method for the synthesis of 2-amine-oxazoles.

BANKING MEMBERS:
Presidente - 1058758 - MARCO EDILSON FREIRE DE LIMA
Interno - 1220404 - CARLOS MAURICIO RABELLO DE SANT ANNA
Interna - 1177598 - ROSANE NORA CASTRO
Externo à Instituição - EUFRÂNIO NUNES DA SILVA JÚNIOR - UFMG
Externa à Instituição - ANDREA ROSANE DA SILVA - CEFET/RJ
Externa à Instituição - WANDA PEREIRA ALMEIDA - UNICAMP
Externo à Instituição - BAUER DE OLIVEIRA BERNARDES - CEFET/RJ