Synthesis and Evaluation of Non-peptidic Cysteine Protease Inhibitors of P. falciparum Derived from Etacrynic Acid

Dude, Marie-Adrienne; Kaeppler, Ulrich; Herb, Monika; Schiller, Markus; Schulz, F. A.; Vedder, Birgit; Heppner, Saskia; Pradel, Gabriele; Gut, Jiří; Rosenthal, Philip J.; Schirmeister, Tanja; Leippe, Matthias; Gelhaus, Christoph

doi:10.3390/molecules14010019

Cited by 10 publications

(8 citation statements)

References 31 publications

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“…The biotinylated compound (Fig. (13)) is a moderate inhibitor of Falcipain 2 and 3 and also displays modest activity against the W2 strain of P. falciparum [137].…”

Section: Falcipain Inhibitorsmentioning

confidence: 99%

Proteases of Plasmodium falciparum as Potential Drug Targets and Inhibitors Thereof

Wegscheid-Gerlach¹,

Gerber²,

Diederich

2010

CTMC

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Malaria, caused by protozoa of the genus Plasmodium, remains one of the most dreadful infectious diseases worldwide killing more than 1 million people per year. The emergence of multidrug-resistant parasites highly demands a steadfast and continuous search not only for new targets but also for new anti-infectives addressing the known ones. As proteases in general have been proven to be excellent drug targets and the development of inhibitors has frequently resulted in approved drugs, this review will only focus on the proteases of Plasmodium falciparum as drug targets. The completion of the sequencing of the Plasmodium falciparum genome in 2002 lead to the discovery of nearly 100 putative proteases encoded therein. Within this review, only those proteases and inhibitors thereof will be discussed in more detail, in which their biological function has been determined undoubtedly or in those cases, in which the development of specific inhibitors has significantly contributed to the understanding of the underlying biological role of the respective protease thus validating the role as promising drug target.

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“…The biotinylated compound (Fig. (13)) is a moderate inhibitor of Falcipain 2 and 3 and also displays modest activity against the W2 strain of P. falciparum [137].…”

Section: Falcipain Inhibitorsmentioning

confidence: 99%

Proteases of Plasmodium falciparum as Potential Drug Targets and Inhibitors Thereof

Wegscheid-Gerlach¹,

Gerber²,

Diederich

2010

CTMC

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“…Compound 24 was identified as the best FPs inhibitor. The investigators recommended future studies to evaluate the affinity binding properties of the identified compound, and to synthesize further peptidomimetic CPIs with etacrynic acid amides [134] .…”

Section: C] Peptidomimetic Inhibitorsmentioning

confidence: 99%

Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part III: Protozoa (2): Plasmodium spp.

Abaza

2019

Parasitologists United Journal

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“…The falcipain-3 inhibitors used in the QSAR studies were taken from a recent series of papers [4,10,11]. The geometries of ligands were optimized by the conjugate gradient method of energy minimization with the Tripos force field and Gasteiger-Hückel charges for all atoms until a gradient of 0.01 kcal mol −1 Å −1 was reached.…”

Section: Preparation Of the Ligand For Dockingmentioning

confidence: 99%

“…They have been found to be localized in the food vacuole, and are able to degrade hemoglobin [3]. So far, several peptidic, peptidomimetic, as well as nonpeptidic cysteine protease inhibitors have been synthesized and tested against malaria parasites [4].…”

Section: Introductionmentioning

confidence: 99%

De novo design of 7-aminocoumarin derivatives as novel falcipain-3 inhibitors

2011

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The availability of the crystal structure of falcipain-3, knowledge of the peptides carrying the 7-aminocoumarin moiety as falcipain-3 ligands/substrates, and a need for new antimalarial agents stimulated us to look at the possibility of finding some novel falcipain-3 inhibitors. In this paper, we report the effect of substitution at the 7-amino position of the coumarin nucleus on the inhibition of falcipain-3, which is a well-validated antimalarial target. The de novo drug design was assisted by QSAR studies that shed light on the binding patterns of known and the newly designed inhibitors, thus taking this discovery process to the next level.

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Synthesis and Evaluation of Non-peptidic Cysteine Protease Inhibitors of P. falciparum Derived from Etacrynic Acid

Cited by 10 publications

References 31 publications

Proteases of Plasmodium falciparum as Potential Drug Targets and Inhibitors Thereof

Proteases of Plasmodium falciparum as Potential Drug Targets and Inhibitors Thereof

Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part III: Protozoa (2): Plasmodium spp.

De novo design of 7-aminocoumarin derivatives as novel falcipain-3 inhibitors

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