Banca de DEFESA: CARLA CAROLINE RIBEIRO DE MENDONCA
Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : CARLA CAROLINE RIBEIRO DE MENDONCA
DATE: 27/10/2022
TIME: 09:00
LOCAL: Link de acesso para videoconferência: https://meet.google.com/rvk-nuqz-iub
TITLE:
Employing QSAR to design synthetic accessible TRPM8 Inhibitors
KEY WORDS:
Transient Receptor Potential Melastatin 8; TRPM8; Antagonist; Rational planning; QSAR.
PAGES: 82
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:
In this work, 53 α-phenylglycine amides described by KOBAYASHI et al. (2016)
and (2021) were subjected to analysis by a diverse range of in silico approaches such
as activity cliff, molecular docking, molecular dynamics and QSAR-3D model building.
This with the objective of optimizing its structure for the elaboration of more assertive
prototypes to inhibit TRPM8. It is a non-selective ion channel, with polymodal
activation, which is related to some diseases such as migraine, overactive bladder and
prostate cancer. The structures have a consolidated synthetic route, as well as the
proposed prototypes. In silico studies were used to predict the 3D properties of
structures derived from existing ones with the hybrid QSAR model that presented
acceptable statistical results (R2 Adj = 0.87, Q2 loo = 0.86, Q2 ext = 0.75). Therefore, the
results obtained indicate that it can describe the relationship between structure and
activity. With all the information, it was seen that four prototypes for having predictive
pIC50 > 7.0, with one highlighted for having predictive pIC50 > 8.1, and other interesting
pharmacokinetic properties, are options for optimizing the most promising compound
of pIC50 = 6.68 activity described by KOBAYASHI and collaborators (2021). Therefore,
such compounds can be synthesized and studied for the development of new drugs.
COMMITTEE MEMBERS:
Externo à Instituição - EDEILDO FERREIRA DA SILVA JUNIOR - UFAL
Presidente - 1893445 - EUZEBIO GUIMARAES BARBOSA
Interna - 1055045 - MARCELA ABBOTT GALVAO URURAHY