Targeting the hTRPV6 with capsaicinoid inhibitors (2019)
- Authors:
- Autor USP: CUNHA, MICAEL RODRIGUES - FCF
- Unidade: FCF
- Sigla do Departamento: FBF
- Subjects: QUÍMICA FARMACÊUTICA; NEOPLASIAS
- Agências de fomento:
- Language: Inglês
- Abstract: Capsaicin is a substance produced by Capsicum peppers with extensive biological activity reported in the literature. Among these studies, it was suggested that the anti-tumor activity is related to modulation of the Transient Potential Receptor Vanilloid (TRPV) channels. Capsaicin is known to bind with very high affinity to TRPV1 ('IC IND. 50' ≈ 7 nM), triggering the burning sensation followed by analgesia. However, recent studies have suggested that the pro-apoptotic effects of capsaicin are TRPV6-mediated. Herein we report the development of a novel inhibitor of the TRPV6 using two different strategies for compounds design. We generated a series of direct and chimeric capsaicinoids based on the literature compounds, capsaicin, and cis-22a. These analogs were probed against HEK-hTRPV6 and the hits were further optimized. Based on the previous SAR and chemical optimization, we found 56h, named MRC-130, a derivative that remarkably inhibited TRPV6 in the nanomolar range ('IC IND. 50' = 83 ± 4 nM), possess high selectivity and stability in vitro, and lesser hERG inhibition compared to the reference compound, cis-22a. It is expected that these new molecules would contribute significantly to the study on the TRPV6 function and its role in tumor pathophysiology
- Imprenta:
- Data da defesa: 03.12.2019
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ABNT
CUNHA, Micael Rodrigues. Targeting the hTRPV6 with capsaicinoid inhibitors. 2019. Tese (Doutorado) – Universidade de São Paulo, São Paulo, 2019. Disponível em: http://www.teses.usp.br/teses/disponiveis/9/9138/tde-10122019-105212/. Acesso em: 23 abr. 2024. -
APA
Cunha, M. R. (2019). Targeting the hTRPV6 with capsaicinoid inhibitors (Tese (Doutorado). Universidade de São Paulo, São Paulo. Recuperado de http://www.teses.usp.br/teses/disponiveis/9/9138/tde-10122019-105212/ -
NLM
Cunha MR. Targeting the hTRPV6 with capsaicinoid inhibitors [Internet]. 2019 ;[citado 2024 abr. 23 ] Available from: http://www.teses.usp.br/teses/disponiveis/9/9138/tde-10122019-105212/ -
Vancouver
Cunha MR. Targeting the hTRPV6 with capsaicinoid inhibitors [Internet]. 2019 ;[citado 2024 abr. 23 ] Available from: http://www.teses.usp.br/teses/disponiveis/9/9138/tde-10122019-105212/
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