Banca de QUALIFICAÇÃO: MARINA BRANDÃO DA FONSECA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : MARINA BRANDÃO DA FONSECA
DATE: 10/05/2024
TIME: 13:00
LOCAL: Online
TITLE:

Synthesis and evaluation of 1,3,5-triazine hybrids with potential TSSK and EPPIN inhibitory activity aiming at non-hormonal male contraceptive action.

KEY WORDS:

spermatogenesis, motility, sperm.

PAGES: 20
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUMMARY:

The number of unintended pregnancies exceeded 120 million cases in the year
2022. Currently available contraceptive methods are predominantly aimed at
women. Methods intended for men include mainly condoms, withdrawal, and
vasectomy. Hormonal methods for male contraceptives are not ideal due to the
potential side effects of testosterone modulation, thus necessitating and
justifying the search for new non-hormonal contraceptive methods for the male
population. The development of non-hormonal male contraceptive drugs targets
spermatogenesis or sperm function. The protein kinase TSSK and the serine
protease EPPIN are highlighted. Studies have shown that the pyrimidine
compound named compound 19 is a promising inhibitor of TSSK 1 and 2 (key
proteins in spermatogenesis); however, its inhibition of other kinases
necessitates refinement of the molecule's selectivity profile. The triazine named
EP055 is a compound with proven inhibitory action on EPPIN (essential for
sperm motility), but further in vivo studies are needed. The objective of this
project is to synthesize a series of hybrid 1,3,5-triazines, with structural
characteristics similar to compound 19 and EP055, that could act as non-
hormonal male contraceptives. A hybrid drug that acts on different mechanisms
of action (spermatogenesis and sperm function) is beneficial because it allows
for continuous use or use only a few hours before sexual activity. Based on the
above, a series of 1,3,5-triazine hybrids was designed aiming for: optimization
of selectivity for TSSK over ALK; modification of toxic groups; and exploring
possible interactions by adding bulky groups. Subsequently, biological
evaluation is necessary to confirm interaction with the proposed proteins and
contraceptive action. The proposed assays aim to evaluate interaction with
target proteins and evaluate their influence on sperm motility.

COMMITTEE MEMBERS:
Presidente - 1220404 - CARLOS MAURICIO RABELLO DE SANT ANNA
Interno - 3292567 - EDUARDO HILLMANN WANDERLIND
Externa à Instituição - MARIA LETÍCIA DE CASTRO BARBOSA - UFJF