Identification of Novel Zika Virus Inhibitors: A Screening using Thiosemicarbazones and Thiazoles Templates.

Autor: de Moraes Gomes PAT; Laboratory of Virology and Experimental Therapy, Federal University of Pernambuco, Recife, Brazil.; Laboratory of Medicinal Chemistry Planning, Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, Recife, PE, Brazil., Barros Freitas LA; Laboratory of Medicinal Chemistry Planning, Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, Recife, PE, Brazil., Pessoa Siqueira LR; Laboratory of Medicinal Chemistry Planning, Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, Recife, PE, Brazil., da Conceição JM; Laboratory of Medicinal Chemistry Planning, Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, Recife, PE, Brazil., Dos Santos IR; Laboratory of Medicinal Chemistry Planning, Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, Recife, PE, Brazil., Pinto AF; Laboratory of Medicinal Chemistry Planning, Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, Recife, PE, Brazil., de Melo Silva VG; Laboratory of Medicinal Chemistry Planning, Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, Recife, PE, Brazil., Nunes JS; Laboratory of Medicinal Chemistry Planning, Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, Recife, PE, Brazil., de Oliveira Cardoso MV; Laboratory of Prospecting of Bioactive Molecules, University of Pernambuco (UPE), Petrolina, PE, Brazil., Pena LJ; Laboratory of Virology and Experimental Therapy, Federal University of Pernambuco, Recife, Brazil., Lima Leite AC; Laboratory of Medicinal Chemistry Planning, Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, Recife, PE, Brazil.
Jazyk: angličtina
Zdroj: Current topics in medicinal chemistry [Curr Top Med Chem] 2023; Vol. 23 (6), pp. 426-439.
DOI: 10.2174/1568026623666221222124433
Abstrakt: Background: Zika virus (ZIKV) remains an important cause of congenital infection, fetal microcephaly, and Guillain-Barré syndrome in the population. In 2016, WHO declared a cluster of microcephaly cases and other neurological disorders reported as a global public health emergency in Brazil. There is still no specific treatment for Zika virus fever, only palliative care. Therefore, there is a need for new therapies against this disease. According to the literature, thiosemicarbazone, phthalimide and thiazole are privileged structures with several biological activities, including antiviral activity against various viruses.
Objective: Based on this, this work presents an antiviral screening using previously synthesized compounds derived from thiosemicarbazone, phthalimide, and thiazole as new hits active against ZIKV.
Methods: After synthesis and characterization, all compounds were submitted to Cytotoxicity by MTT and Antiviral activity against ZIKV assays.
Results: Compounds 63, 64, 65, and 73 exhibited major reductions in the ZIKV title from this evaluation. Compounds 63 (99.74%), 64 (99.77%), 65 (99.92%), and 73 (99.21%) showed a higher inhibition than the standard 6MMPr (98.74%) at the CC20 dose. These results revealed new chemical entities with anti-ZIKV activity.
Conclusion: These derivatives are promising candidates for further assays. In addition, the current approach brings a new privileged scaffolding, which may drive future drug discovery for ZIKV.
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Databáze: MEDLINE