Vanillin-Related N-Acylhydrazones: Synthesis, Antischistosomal Properties and Target Fishing Studies

Autor(es):Mostrar menos -

Rando, Daniela G. G. ^[1] ; da Costa, Marcela O. L. ^[1] ; Pavani, Thais F. A. ^[1] ; Oliveira, Thiago ^[1] ; dos Santos, Paloma F. ^[1] ; Amorim, Carina R. ^[1] ; Pinto, Pedro L. S. ^[2] ; de Brito, Mariana G. ^[3] ; Silva, Marcos P. N. ^[3] ; Roquini, Daniel B. ^[3] ; de Moraes, Josue ^[3]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Ciencias Farmaceut, Inst Ciencias Ambientais Quim & Farmaceut, Grp Pesquisas Quimicofarmaceut, Diadema, SP - Brazil

^[2] Adolfo Lutz Inst, Nucleo Enteroparasitas, Sao Paulo, SP - Brazil

^[3] Univ Guarulhos, Nucleo Pesquisa Doencas Negligenciadas, Praca Tereza Cristina 229, BR-07023070 Guarulhos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CURRENT TOPICS IN MEDICINAL CHEMISTRY; v. 19, n. 14, p. 1241-1251, 2019.
• Citações Web of Science: 1

Resumo

Background: Schistosomiasis is a neglected disease, which affects millions of people in developing countries. Its treatment relies on a single therapeutic alternative, the praziquantel. This situation may lead to drug resistance which, in turn, made urgent the need for new antischistosomal agents. N-acylhydrazones are usually explored as good antimicrobial agents, but the vanillin-related N-acylhydrazones have never been tested by their antiparasitic potential. Objective: Herein, we report the synthesis of seven analogues, three of them unpublished, their biological investigation against Schistosoma mansoni and Target Fishing studies. Methods: The compounds were synthesized following classical synthetical approaches. The anthelmintic potential was assessed as well as their cytotoxicity profile. Confocal laser scanning microscopy and target fishing study were performed to better understand the observed antischistosomal activity. Results: Compound GPQF-407 exhibited good antischistosomal activity (47.91 mu M) with suitable selec ivity index (4.14). Confocal laser scanning microscopy revealed that it triggered severe tegumental destruction and tubercle disintegration. Target fishing studies pointed out some probable targets, such as the serine-threonine kinases, dihydroorotate dehydrogenases and carbonic anhydrase II. Conclusion: The GPQF-407 was revealed to be a promising antischistosomal agent which, besides presenting the N-acylhydrazone privileged scaffold, also could be easily synthesized on large scales from commercially available materials. (AU)

• Processo FAPESP: 16/22488-3 - Reposicionamento de fármacos para doenças negligenciadas: identificação de novos agentes anti-helmínticos
• Beneficiário: Josué de Moraes
• Modalidade de apoio: Auxílio à Pesquisa - Regular