2-acylamino-5-nitro-1,3-thiazoles: preparation and in vitro bioevaluation against four neglected protozoan parasites

Bioorganic & Medicinal Chemistry
Carlos Nava-ZuazoGabriel Navarrete-Vázquez

Abstract

The 2-acylamino-5-nitro-1,3-thiazole derivatives (1-14) were prepared using a one step reaction. All compounds were tested in vitro against four neglected protozoan parasites (Giardia intestinalis, Trichomonas vaginalis, Leishmania amazonensis and Trypanosoma cruzi). Acetamide (9), valeroylamide (10), benzamide (12), methylcarbamate (13) and ethyloxamate (14) derivatives were the most active compounds against G. intestinalis and T. vaginalis, showing nanomolar inhibition. Compound 13 (IC50=10nM), was 536-times more active than metronidazole, and 121-fold more effective than nitazoxanide against G. intestinalis. Compound 14 was 29-times more active than metronidazole and 6.5-fold more potent than nitazoxanide against T. vaginalis. Ureic derivatives 2, 3 and 5 showed moderate activity against L. amazonensis. None of them were active against T. cruzi. Ligand efficiency indexes analysis revealed higher intrinsic quality of the most active 2-acylamino derivatives than nitazoxanide and metronidazole. In silico toxicity profile was also computed for the most active compounds. A very low in vitro mammalian cytotoxicity was obtained for 13 and 14, showing selectivity indexes (SI) of 246,300 and 141,500, respectively. Nitazoxanide showed...Continue Reading

References

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Citations

Jul 2, 2015·Future Medicinal Chemistry·José L Medina-FrancoOscar Méndez-Lucio
Apr 5, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Emanuel Hernández-NúñezGabriel Navarrete Vázquez
Aug 7, 2018·PLoS Neglected Tropical Diseases·Kelly M HennesseyKayode K Ojo
Aug 15, 2017·Parasitology·Rebecca L CharltonPatrick G Steel
Dec 1, 2015·Frontiers in Microbiology·Amir AzamKamal Ahmad
Jun 12, 2020·Parasitology Research·Brenda Petró-SilveiraTiana Tasca
Jan 29, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anca-Maria BorceaOvidiu Oniga
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Sep 2, 2020·Journal of Medicinal Chemistry·Andrew RichesTina S Skinner-Adams

Related Concepts

Schizonticides
Protozoan Infections
Thiazoles
Drug Modeling
Analogs & derivatives
Giardia lamblia
Ligands
Metronidazole
Trichomonas vaginalis
Trypanosoma cruzi

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