Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain

Chiyanzu, Idan; Hansell, Elizabeth; Gut, Jiří; Rosenthal, Philip J.; McKerrow, James H.; Chibale, Kelly

doi:10.1016/s0960-894x(03)00756-x

Cited by 138 publications

(80 citation statements)

References 16 publications

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“…As far as nonpeptide FP inhibitors are concerned (Fig. 9), these include chalcones [108], which are biosynthetic precursors of flavonoids, isoquinolines [95,96] and thiosemicarbazones [109].…”

Section: Falcipain Inhibitors: Potential Antimalarial Drugsmentioning

confidence: 99%

Falcipains, Plasmodium falciparum Cysteine Proteases as Key Drug Targets Against Malaria

Teixeira¹,

Gomes²,

Gomes

2011

CMC

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There is a high demand for new drugs against malaria, which takes millions of lives annually. The abuse of classical antimalarials from the late 1940's to the early 1980's has bred resistant parasites, which led to the use of more potent drugs that ended up by refueling the resistance cycle. An example is chloroquine, once highly effective but now virtually useless against malaria.Structure-based rational drug design relies on high-resolution target structures to allow for screening of selective ligands/inhibitors. For the past two decades, and especially after the unveiling of the Plasmodium falciparum genome in 2002, enzymes of this lethal malaria parasite species have been increasingly attracting the attention of Medicinal Chemists worldwide as promising drug targets. There is particular emphasis on proteases having key roles on the degradation of host's hemoglobin within the food vacuole of blood-stage parasites, as these depend on such process for their survival. Among such enzymes, Plasmepsins (aspartic proteases) and, especially, Falcipains (cysteine proteases) are highly promising antimalarial drug targets. The present review will focus on the computational approaches made so far towards the unraveling of the structure, function and inhibition of Falcipains that, by virtue of their quite specific features, are excellent targets for highly selective inhibitors.

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Section: Falcipain Inhibitors: Potential Antimalarial Drugsmentioning

confidence: 99%

Falcipains, Plasmodium falciparum Cysteine Proteases as Key Drug Targets Against Malaria

Teixeira¹,

Gomes²,

Gomes

2011

CMC

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“…Alguns autores, efetuaram uma pequena modificação neste método e observaram que as tiossemicarbazonas também poderiam ser sintetizadas em solução neutra indicando que, possivelmente, o emprego do ácido não seria uma condição indispensável para formação dessas moléculas 34,45,46 . Neste sentido, Chiyanzu e colaboradores 46 demonstraram que as tiossemicarbazonas derivadas de isatina, que tinham sido anteriormente obtidas por Karah 15 utilizando o método convencional, também eram facilmente sintetizadas sem o auxílio de catalisadores (Esquema 4b).…”

Section: Esquema 2 Análise Retrossintética De Tiossemicarbazonasunclassified

Tiossemicarbazonas: métodos de obtenção, aplicações sintéticas e importância biológica

Tenório¹,

Góes²,

Lima³

et al. 2005

Quím. Nova

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“…MI-MTSC, MI-DMTSC and their complexes with cobalt(II), nickel(II), and copper(II) ions were prepared and characterized by spectral methods [25]. Other derivatives obtained by substituting groups at different other positions of the isatin and TSC moieties were also reported [12, [26][27][28][29]. In a few of these studies the focus was on obtaining water-soluble analogues of isatin thiosemicarbazone by substituting isatin at the aromatic ring.…”

Section: Introductionmentioning

confidence: 99%

A theoretical investigation on the isomerism and the NMR properties of thiosemicarbazones

Silva

Albu

2007

Open Chemistry

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Hybrid density functional theory calculations at the mPW1PW91/6-31+G(d,p) level of theory have been used to investigate the optimized structures and other molecular properties of five different series of thiosemicarbazones. The investigated compounds were obtained from acenaphthenequinone, isatin and its derivatives, and alloxan. The focus of the study is the isomerism and the NMR characterization of these thiosemicarbazones. It was found that only one isomer is expected for thiosemicarbazones and methylthiosemicarbazones, while for dimethylthiosemicarbazones, two isomers are possible. All investigated thiosemicarbazones exhibit a hydrazinic proton that is highly deshielded and resonates far downfield in the proton NMR spectra. This proton is a part of a characteristic sixmembered ring, and its NMR properties are a result of its strong, intermolecular hydrogen bond. The relationships between the calculated 1 H and 13 C NMR chemical shifts and various geometric parameters are reported.

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Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain

Cited by 138 publications

References 16 publications

Falcipains, Plasmodium falciparum Cysteine Proteases as Key Drug Targets Against Malaria

Falcipains, Plasmodium falciparum Cysteine Proteases as Key Drug Targets Against Malaria

Tiossemicarbazonas: métodos de obtenção, aplicações sintéticas e importância biológica

A theoretical investigation on the isomerism and the NMR properties of thiosemicarbazones

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