Development of a Potent Inhibitor of the <i>Plasmodium</i> Proteasome with Reduced Mammalian Toxicity

LaMonte, Gregory; Almaliti, Jehad; Bibo-Verdugo, Betsaida; Keller, Lena; Zou, Bing; Yang, Jennifer H.; Antonova‐Koch, Yevgeniya; Orjuela-Sánchez, Pamela; Boyle, Colleen A.; Vigil, Edgar; Wang, Lawrence; Goldgof, Gregory M.; Gerwick, Lena; O’Donoghue, Anthony J.; Winzeler, Elizabeth A.; Gerwick, William H.; Ottilie, Sabine

doi:10.1021/acs.jmedchem.7b00671

Cited by 86 publications

(128 citation statements)

References 42 publications

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“…The published in silico models were mostly applied for lead identification/optimization (13 articles) of the known Plasmodium targets (13 targets). Most articles are specific for P. falciparum targets (Campbell et al, 2014;Kumari et al, 2016;LaMonte et al, 2017;Lhouvum et al, 2013;MacDonald and Boyd, 2015;Raza et al, 2017;Ren et al, 2016;Sharma et al, 2016); 3 articles involved target for P. vivax (MacDonald et al, 2015;Rout et al, 2016;Bouillon et al, 2013) and 1 article involved target for liver stage of Plasmodium (Sullivan et al, 2015). Five articles were applied in silico modeling for target identification/validation (Lhouvum et al, 2013;Mehra et al, 2015;Paul et al, 2015;Rout et al, 2015;Pandey et al, 2014).…”

Section: Study Selectionmentioning

confidence: 99%

“…Five articles were applied in silico modeling for target identification/validation (Lhouvum et al, 2013;Mehra et al, 2015;Paul et al, 2015;Rout et al, 2015;Pandey et al, 2014). Both structure-based (Bouillon et al, 2013;LaMonte et al, 2017;MacDonald and Boyd, 2015;Raza et al, 2017;Ren et al, 2016;Rout and Mahapatra, 2016;Sullivan et al, 2015) and ligandbased (Villalobos et al, 2013;Kumari et al, 2016;Ren et al, 2016;Sharma et al, 2016) approaches were applied to obtain lead antimalarial candidates. Two articles also assessed ADMET properties (Ren et al, 2016;Rout and Mahapatra, 2016).…”

Section: Study Selectionmentioning

confidence: 99%

“… Not focusing on in silico modeling  Not focusing on antimalarial drug discovery Campbell et al, 2014;LaMonte et al, 2017;Sullivan et al, 2015). Homology modelling, molecular docking, 2D-or 3D-QSAR and pharmacophore modeling were commonly applied methods.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Lead identification/optimization involved identification of potent antimalarial candidate molecules which are inhibitors of known specific Plasmodium targets (13 targets) encoded by the malaria parasite genome. These included: inosine monophosphate dehydrogenase (IMPDH) (Raza et al, 2017), proteasome (LaMonte et al, 2017), lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) (Ren et al, 2016), heat shock regulated A (HrA or DegP) (Sharma et al, 2016), P. falciparum M18 (Kumari et al, 2016), P. falciparum aspartyl aminopeptidase (PfM18AAP) (Kumari et al, 2016), leucine amino peptidase (M17 LAP) (Rout and Mahapatra, 2016), P. falciparum glycogen synthase kinase-3 (PfGSK-3), P. falciparum CTP synthetase (PfCTPS), choline kinase (PfCK), and glutathione S-transferase (PfGST) (Verma et al, 2015), Plasmodium peptidyl-prolyl cis/trans isomerase (MacDonald and Boyd, 2015), Plasmodium phosphatases, cytochrome bc1 (Jimenez et al, 2013), and P. vivax subtilin-like serine protease (PvSUB1) (Bouillon et al, 2013). Application of the modeling for target identification/validation included Nmyristoyltransferase (NMT) (Paul et al, 2015), Plasmodium phosphatases (Campbell et al, 2014;Pandey et al, 2014), and PFI1625c metalloprotease (Lhouvum et al, 2013).…”

Section: Study Characteristicsmentioning

confidence: 99%

See 3 more Smart Citations

A systematic review: Application of in silico models for antimalarial drug discovery

Cheoymang¹,

Na‐Bangchang²

2018

Afr. J. Pharm. Pharmacol.

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Malaria remains the global public health problem due to the reemergence of drug resistance. There is an urgent need for development of new antimalarial candidates which are effective against resistant malaria parasite. This systematic review evaluates the published research studies that applied in silico modeling during the discovery process of antimalarial drugs. Literature searches were conducted using PubMed, EBSCO, EMBASE, and Web of Science to identify the relevant articles using the search terms "Malaria" "In silico model", "Computer-based drug design", "Antimalarial drug", and "Drug discovery". Only the articles published in English between 2008 and May 2015 were included in the analysis. A total of 17 relevant articles met the search criteria. Most articles are studies specific to Plasmodium falciparum targets; 3 and 1 articles, respectively involve target for P. vivax and liver stage of Plasmodium. Both structure-based and ligand-based approaches were applied to obtain lead antimalarial candidates. Two articles also assessed absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Confirmation of activity of the candidate leads by in vitro and/or in vivo assays were reported in some studies. Homology modelling, molecular docking, 2D-or 3D-QSAR and pharmacophore modeling are commonly applied methods. One study used de novo synthesis for lead identification and one study applied phylogenetic analysis for target identification/validation.

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Section: Study Selectionmentioning

confidence: 99%

Section: Study Selectionmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

See 2 more Smart Citations

A systematic review: Application of in silico models for antimalarial drug discovery

Cheoymang¹,

Na‐Bangchang²

2018

Afr. J. Pharm. Pharmacol.

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show abstract

“…Actualmente se adelantan proyectos para combatir la resistencia que se presenta a los Universidad de Manizales -Facultad de Ciencias de la Salud medicamentos convencionales, principalmente en el continente Africano. Uno de estos medicamentos es carmoficina B, que actúa inhibiendo tanto la etapa sexual como asexual de la infección, siendo la subunidad β5 del proteosoma su blanco molecular [47].…”

Section: Perspectivas Futurasunclassified

Malaria, enfermedad tropical de múltiples métodos diagnósticos

Moreno

Sánchez

Giraldo

et al. 2017

archmed

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La malaria es una enfermedad causada por el parasito de género Plasmodium, que se transmite mediante la picadura de la hembra del mosquito Anopheles. Entre los años 2000 a 2015 se han reportado 212 millones de casos a nivel mundial. En Colombia, la malaria es considerada un problema de salud pública, se estima que al menos el 70% del territorio cuenta con las condiciones ecológicas necesarias para la transmisión del parasito. Para evitar el aumento en el número de casos de malaria, se utilizan 3 pilares de prevención: evitar la exposición y realizar control del vector, quimioprofilaxis y diagnóstico oportuno. Después de este último, se debe brindar el tratamiento, cuyos objetivos son: curación clínica del paciente, curación radical de la infección y control de la transmisión. Para el diagnóstico, existen diferentes métodos, los cuales se evalúan y diferencian de acuerdo a la sensibilidad y especificidad; con base en esto, se define el Gold Standard, como prueba de referencia. En la actualidad, el Gold Standard para el diagnóstico de malaria es un método microscópico: gota gruesa. Sin embargo, existen otros métodos: extendido de sangre periférica, métodos moleculares y métodos serológicos.

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Drug Discovery and Development for Kinetoplastid Diseases

Caffrey

Steverding

Ferreira

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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In this article, we review the disease, biology, and biochemistry of kinetoplastids, as well as the new drugs and drug candidates that have entered the clinic in the last decade. We also describe examples of the preclinical exploration of small molecules against various protein targets (e.g. cysteine proteases, the proteasome, and tubulin), as well as cutting‐edge molecular and computational strategies and technologies being brought to bear to discover and develop new antitrypanosomal drugs. For comprehensive descriptions of the disease, biology, and drug therapies prior to 2011, the reader is encouraged to review the article by P.M. Woster that appeared in 2010 in the seventh edition of Burger's Medicinal Chemistry, Drug Discovery, and Development, entitled Antiprotozoal/Antiparasitic Agents.

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Development of a Potent Inhibitor of the Plasmodium Proteasome with Reduced Mammalian Toxicity

Cited by 86 publications

References 42 publications

A systematic review: Application of in silico models for antimalarial drug discovery

A systematic review: Application of in silico models for antimalarial drug discovery

Malaria, enfermedad tropical de múltiples métodos diagnósticos

Drug Discovery and Development for Kinetoplastid Diseases

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