Synthesis of new 3-acetyl-1,3,4-oxadiazolines combined with pyrimidines as antileishmanial and antiviral agents

合成新的 3-乙酰基-1,3,4-恶二唑啉与嘧啶联合用作抗利什曼原虫和抗病毒药物

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作者:Saida Lachhab, Az-Eddine El Mansouri, Ahmad Mehdi, Indira Dennemont, Johan Neyts, Dirk Jochmans, Graciela Andrei, Robert Snoeck, Yogesh S Sanghvi, Mustapha Ait Ali, Philippe M Loiseau, Hassan B Lazrek

Abstract

A new series of 3-acetyl-1,3,4-oxadiazoline hybrid molecules was designed and synthesized using a condensation between acyclonucleosides and substituted phenylhydrazone. All intermediates and final products were screened against Leishmania donovani, a Protozoan parasite and against three viruses SARS-CoV-2, HCMV and VZV. While no significant activity was observed against the viruses, the intermediate with 6-azatymine as thymine and 5-azathymine-3-acetyl-1,3,4-oxadiazoline hybrid exhibited a significant antileishmanial activity. The later compound was the most promising, exhibiting an IC50 value at 8.98 µM on L. donovani intramacrophage amastigotes and a moderate selectivity index value at 2.4.

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