Phenylhydrazides as inhibitors of Leishmania amazonensis arginase and antileishmanial activity

Lima, E.C.D.; Branco, Frederico Silva Castelo; Maquiaveli, Claudia do Carmo; Farias, André Borges; Rennó, Magdalena N.; Boechat, Núbia; Silva, Edson R.

doi:10.1016/j.bmc.2019.07.022

Cited by 18 publications

(18 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16 The lactam 5 could also be acylated to give 7 in 94% yield with nearly no reduction in the product dr and er values. 17 The lactone ring of the chiral product 3a could be opened by BnNH2 via an ester-to-amide exchange to give 8 with a good yield and er value, 18 although the diastereoselectivity slightly dropped. The acidic carbon of the malonate moiety on 3a could react with alkyl bromides 19 (products 9 and 10) under basic conditions.…”

Section: Resultsmentioning

confidence: 99%

Umpolung of donor–acceptor cyclopropanesviaN-heterocyclic carbene organic catalysis

et al. 2021

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Umpolung of donor–acceptor cyclopropanesviaN-heterocyclic carbene organic catalysis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The first synthetic L-ARG inhibitor, containing a thiosemicarbazide as a key pharmacophoric element, showed a selective parasite inhibition, but failed to kill the parasite efficiently in vitro [27,28]. Recently, a series of synthetic compounds, containing a phenilhydrazides moiety were described as a new pharmacophoric group that targets L-ARG, and kills the L. amazonensis promastigotes in vitro [29].…”

Section: Discussionmentioning

confidence: 99%

Cinnamides Target Leishmania amazonensis Arginase Selectively

et al. 2020

View full text Add to dashboard Cite

Caffeic acid and related natural compounds were previously described as Leishmania amazonensis arginase (L-ARG) inhibitors, and against the whole parasite in vitro. In this study, we tested cinnamides that were previously synthesized to target human arginase. The compound caffeic acid phenethyl amide (CAPA), a weak inhibitor of human arginase (IC50 = 60.3 ± 7.8 μM) was found to have 9-fold more potency against L-ARG (IC50 = 6.9 ± 0.7 μM). The other compounds that did not inhibit human arginase were characterized as L-ARG, showing an IC50 between 1.3–17.8 μM, and where the most active was compound 15 (IC50 = 1.3 ± 0.1 μM). All compounds were also tested against L. amazonensis promastigotes, and only the compound CAPA showed an inhibitory activity (IC50 = 80 μM). In addition, in an attempt to gain an insight into the mechanism of competitive L-ARG inhibitors, and their selectivity over mammalian enzymes, we performed an extensive computational investigation, to provide the basis for the selective inhibition of L-ARG for this series of compounds. In conclusion, our results indicated that the compounds based on cinnamoyl or 3,4-hydroxy cinnamoyl moiety could be a promising starting point for the design of potential antileishmanial drugs based on selective L-ARG inhibitors.

show abstract

“…The compounds were tested against L. amazonensis promastigotes and some of them were submitted to molecular docking experiments in order to obtain further information about their potential binding mode. The best-acting compound in the L. amazonensis promastigotes assay ( 47 , Figure , EC 50 of 12.7 μM), showed interactions with relevant residues, which are conserved in arginase family enzymes and involved in the coordination of the binuclear manganese cluster within the active site …”

Section: Arginasementioning

confidence: 99%

Metalloenzyme Inhibitors against Zoonotic Infections: Focus on Leishmania and Schistosoma

Rossi,

Tudino,

Carullo

et al. 2024

ACS Infect. Dis.

View full text Add to dashboard Cite

The term "zoonosis" denotes diseases transmissible among vertebrate animals and humans. These diseases constitute a significant public health challenge, comprising 61% of human pathogens and causing an estimated 2.7 million deaths annually. Zoonoses not only affect human health but also impact animal welfare and economic stability, particularly in low-and middleincome nations. Leishmaniasis and schistosomiasis are two important neglected tropical diseases with a high prevalence in tropical and subtropical areas, imposing significant burdens on affected regions. Schistosomiasis, particularly rampant in sub-Saharan Africa, lacks alternative treatments to praziquantel, prompting concerns regarding parasite resistance. Similarly, leishmaniasis poses challenges with unsatisfactory treatments, urging the development of novel therapeutic strategies. Effective prevention demands a One Health approach, integrating diverse disciplines to enhance diagnostics and develop safer drugs. Metalloenzymes, involved in parasite biology and critical in different biological pathways, emerged in the last few years as useful drug targets for the treatment of human diseases. Herein we have reviewed recent reports on the discovery of inhibitors of metalloenzymes associated with zoonotic diseases like histone deacetylases (HDACs), carbonic anhydrase (CA), arginase, and heme-dependent enzymes.

show abstract

Phenylhydrazides as inhibitors of Leishmania amazonensis arginase and antileishmanial activity

Cited by 18 publications

References 35 publications

Umpolung of donor–acceptor cyclopropanesviaN-heterocyclic carbene organic catalysis

Umpolung of donor–acceptor cyclopropanesviaN-heterocyclic carbene organic catalysis

Cinnamides Target Leishmania amazonensis Arginase Selectively

Metalloenzyme Inhibitors against Zoonotic Infections: Focus on Leishmania and Schistosoma

Contact Info

Product

Resources

About