Banca de QUALIFICAÇÃO: RITA YANKA PEREIRA DA SILVA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : RITA YANKA PEREIRA DA SILVA
DATE: 15/12/2025
TIME: 09:00
LOCAL: VIDEOCONFERÊNCIA
TITLE:

Similarity-Based Profiling of Hydrazone-Containing Scaffolds Active Against Leishmania Amastigotes

KEY WORDS:

Naphthoquinones; triazoles; medicinal chemistry; Chagas disease; dihydroorotate dehydrogenase.

PAGES: 105
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

Naphthoquinones are a class of chemical compounds whose main characteristic is redox action induced by the aromatic system. This property is responsible for several biological activities, including antiparasitic and antiproliferative actions. Another class of compounds with various reported biological activities are triazoles, whose lipophilicity is important, especially for activity against intracellular antigens, as it favors passage through the cell membrane. The trypanocidal activity of naphthoquinones and triazoles has been investigated and proven in recent years, since Chagas disease is a neglected tropical disease for which available drugs were discovered more than 50 years ago, and the parasite has already developed resistance mechanisms to most of them, making treatment difficult. Furthermore, treatment is costly, prolonged, and causes many adverse effects, reducing patient adherence. Another disease with a global impact, which is one of the leading causes of death on the planet, and for which the development of safer and more effective therapies is necessary, is cancer. Many approaches prolong and improve quality of life, but mortality caused by the disease remains high. In this work, molecules with the 1,4-naphthoquinone core associated with triazole cores are being synthesized and tested against dihydroorotate dehydrogenase (DHODH), an enzyme related to RNA and DNA synthesis in proliferating cells, against Trypanosoma cruzi, and against Acute Myeloid Leukemia cell lines (MOLM-13 and THP-1). The produced molecular structures are being subjected to virtual screening for the prediction of possible biological targets, and confirmatory tests are being performed to validate the targets. DHODH was one of the targets identified in the screening, and in the inhibition assay against the enzyme, the 4g molecule showed a high percentage of inhibition, even higher than that of the standard. In antiproliferative assays against leukemia cell lines, the 2h compound stood out for its high potency against several cell lines and low IC50.

COMMITTEE MEMBERS:
Presidente - 1239642 - ALISSON MACARIO DE OLIVEIRA
Externa à Instituição - DAYSE CAROLINE SEVERIANO DA CUNHA - UFRN
Externo ao Programa - 1803692 - FABRICIO GAVA MENEZES - null