2. Academic Validation
  3. Novel Diacyl-hydrazide Compounds as Potential Therapeutics for Visceral Leishmaniasis

Novel Diacyl-hydrazide Compounds as Potential Therapeutics for Visceral Leishmaniasis

  • ACS Omega. 2024 Aug 22;9(35):37170-37182. doi: 10.1021/acsomega.4c04517.
Bernhard Jandl 1 2 3,  Rebecca Zheng 4,  Markus Muttenthaler 1 3,  Jonathan Baell 4 5 6
Affiliations

Affiliations

  • 1 Institute of Biological Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria.
  • 2 Vienna Doctoral School in Chemistry, University of Vienna, 1090 Vienna, Austria.
  • 3 Institute for Molecular Bioscience, The University of Queensland, 4072 Brisbane, Queensland, Australia.
  • 4 Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia.
  • 5 School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, China.
  • 6 Australian Translational Medicinal Chemistry Facility, Monash University, Parkville, Victoria 3052, Australia.
PMID: 39246504 DOI: 10.1021/acsomega.4c04517
Abstract

Visceral leishmaniasis is a neglected tropical disease with the highest mortality among different forms of leishmaniasis manifestation in humans. The disease is caused by the parasitic protists Leishmania donovani and Leishmania infantum, and treatments remain unsuitable due to high costs, complicated administration, lack of efficacy, variable patient susceptibility, toxic side effects, and rising parasitic resistance. Herein, we report a structure-activity relationship (SAR) exploration of the diacyl-hydrazide scaffold identified to have antiparasitic activity from a high-throughput screen against L. donovani, Trypanosoma cruzi, and Trypanosoma brucei. This SAR study revealed new structural insights into this scaffold related to bioactivity resulting in a new series of lead compounds with nanomolar activity against L. donovani and no toxicity against human THP-1 macrophages. These optimized diacyl-hydrazide compounds set the stage for future drug development and hold promise for a new treatment avenue for visceral leishmaniasis.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z