Structure-Activity Relationship Studies of 9-Alkylamino-1,2,3,4-tetrahydroacridines against Leishmania (Leishmania) infantum Promastigotes

• Tipo: Artigo em Revista Científica Internacional
• Data: 2023

Autores

Silva, CFM (Autor) Outra; Leao, T (Autor) Outra; Dias, F (Autor) Outra; Tomas, AM (Autor) Outra; Pinto, DCGA (Autor) Outra; Oliveira, EFT (Autor) Outra; Oliveira, A (Autor) Outra; Pedro A Fernandes (Autor) FCUP; Silva, AMS (Autor) Outra

Revista

Título: Pharmaceutics

Vol. 15

Página Final: 669

ISSN: 1999-4923

Editora: MDPI

Indexação

ISI Web of Knowledge - 1 Citação

Scopus

Outras Informações

ID Authenticus: P-00Y-2M5

DOI: 10.3390/pharmaceutics15020669

Abstract (EN): Leishmaniasis is one of the most neglected diseases in modern times, mainly affecting people from developing countries of the tropics, subtropics and the Mediterranean basin, with approximately 350 million people considered at risk of developing this disease. The incidence of human leishmaniasis has increased over the past decades due to failing prevention and therapeutic measures-there are no vaccines and chemotherapy, which is problematic. Acridine derivatives constitute an interesting group of nitrogen-containing heterocyclic compounds associated with numerous bioactivities, with emphasis to their antileishmanial potential. The present work builds on computational studies focusing on a specific enzyme of the parasite, S-adenosylmethionine decarboxylase (AdoMet DC), with several 1,2,3,4-tetrahydro-acridines emerging as potential inhibitors, evidencing this scaffold as a promising building block for novel antileishmanial pharmaceuticals. Thus, several 1,2,3,4-tetrahydroacridine derivatives have been synthesized, their activity against Leishmania (Leishmania) infantum promastigotes evaluated and a structure-activity relationship (SAR) study was developed based on the results obtained. Even though the majority of the 1,2,3,4-tetrahydroacridines evaluated presented high levels of toxicity, the structural information gathered in this work allowed its application with another scaffold (quinoline), leading to the obtention of N-1,N-12-bis(7-chloroquinolin-4-yl)dodecane-1,12-diamine (12) as a promising novel antileishmanial agent (IC50 = 0.60 +/- 0.11 mu M, EC50 = 11.69 +/- 3.96 mu M and TI = 19.48).

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 15