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Anti-Parasite Drug Discovery
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Anti-Parasite Drug Discovery

A topical collection in Drugs and Drug Candidates (ISSN 2813-2998). This collection belongs to the section "Medicinal Chemistry and Preliminary Screening".

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Editor

Prof. Dr. Philippe Loiseau

E-Mail Website
Collection Editor
BioCIS, Faculty of Pharmacy, Université Paris-Saclay, CNRS, 91400 Orsay, France
Interests: parasitology; antiparasite chemotherapy; mechanism of action of antiparasite drugs; drug resistance; leishmaniasis
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

I would like to announce an opportunity for you to publish a paper in this Special Issue, entitled “Anti-parasite drug discovery”, published in the new MDPI journal Drugs and Drug Candidates.

This Topical Collection has been launched to provide a forum for the dissemination of the latest studies in this field, including all approaches based on drug design, chemical synthesis, the biological evaluation of new compounds, and their development through the pipeline of drug candidates.

The identification and development of more specific drugs that are less toxic than those presently used in both medical and veterinary clinics are clearly needed for the chemotherapy of parasitic diseases. Such a challenge involves complementary approaches where chemistry is the basis of drug innovation.

In a OneHealth context that implies respect for the environment, virtuous approaches must be considered, including green chemistry through a reduction in the use of toxic solvents, and the reduction in the number of synthesis steps through new synthesis pathways, in order to reduce the cost of anti-parasite drug production (these drugs being mainly used in developing countries).

I hope that you will consider submitting a manuscript for publication in this Topical Collection, which has no deadline, as the accepted manuscripts will be published as they are received.

Prof. Dr. Philippe Loiseau
Collection Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Drugs and Drug Candidates is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • anti-parasite agents
  • drugs
  • drug candidates
  • medicinal chemistry
  • anti-parasite evaluation
  • in vitro and in vivo models
  • pharmacokinetics
  • metabolism
  • toxicity

Published Papers (6 papers)

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2024

Jump to: 2023, 2022

32 pages, 1867 KiB  
Review
Opportunities and Difficulties in the Repurposing of HDAC Inhibitors as Antiparasitic Agents
by Tapas Kumar Mohapatra, Reena Rani Nayak, Ankit Ganeshpurkar, Prashant Tiwari and Dileep Kumar
Drugs Drug Candidates 2024, 3(1), 70-101; https://doi.org/10.3390/ddc3010006 - 18 Jan 2024
Viewed by 737
Abstract
Ongoing therapy for human parasite infections has a few known drugs but with serious side effects and the problem of drug resistance, impelling us to discover novel drug candidates with newer mechanisms of action. Universally, this has boosted the research in the design [...] Read more.
Ongoing therapy for human parasite infections has a few known drugs but with serious side effects and the problem of drug resistance, impelling us to discover novel drug candidates with newer mechanisms of action. Universally, this has boosted the research in the design and development of novel medicinal agents as antiparasitic drugs with a novel mode of action. Histone deacetylase inhibitors (HDACis) are used in a vast variety of diseases due to their anti-inflammatory properties. Drug repurposing strategies have already approved HDACis as cancer therapeutics and are now under investigation for many parasitic infections. Along with the expression of the gene, histone deacetylase (HDAC) enzymes also act as a slice of great multi-subunit complexes, targeting many non-histones, changing systemic and cellular levels signaling, and producing different cell-based specified effects. Zinc (Zn2+)- and nicotinamide adenine dinucleotide (NAD+)-dependent HDACs of parasites play pivotal roles in the alteration of gene expression of parasites. Some of them are already known to be responsible for the survival of several parasites under odd circumstances; thus, targeting them for therapeutic interventions will be novel for potential antiparasitic targets. This point of view outlines the knowledge of both class-I and class-II HDACis and sirtuin inhibitors that emerged to be the key players in the treatment of human parasitic disorders like Leishmaniasis, Schistosomiasis, Malaria, Trypanosomiasis, and Toxoplasmosis. This review also focuses on repurposing opportunities and challenges in HDAC inhibitors that are preceded by their clinical development as potent new antiparasitic drugs. Full article
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2023

Jump to: 2024, 2022

11 pages, 1466 KiB  
Article
Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays
by Camila M. Clemente, Renée Onnainty, Nadina Usseglio, Gladys E. Granero and Soledad Ravetti
Drugs Drug Candidates 2023, 2(3), 770-780; https://doi.org/10.3390/ddc2030038 - 19 Sep 2023
Viewed by 984
Abstract
Based on the demonstrated and reported trypanocidal, leishmanicidal, and antiplasmodial activities of two menthol prodrugs, it was decided to proceed with preformulation studies, which are of key relevance in the drug discovery process. The aim of this study is to examine the stability [...] Read more.
Based on the demonstrated and reported trypanocidal, leishmanicidal, and antiplasmodial activities of two menthol prodrugs, it was decided to proceed with preformulation studies, which are of key relevance in the drug discovery process. The aim of this study is to examine the stability and permeability of two new menthol prodrugs with antiparasitic activity. To determine the stability of menthol and its prodrugs, the corresponding studies were carried out in buffered solutions at pH values of 1.2, 5.8, and 7.4 at 37 °C. In silico permeability studies were performed using the free PerMM software and then in vitro permeability studies were performed using a biomimetic artificial membrane (BAM). Permeability studies conducted in silico predicted that both menthol and its prodrugs would pass through biological membranes via flip-flop movement. This prediction was subsequently confirmed by in vitro BAM permeability studies, where it was observed that the menthol prodrugs (1c and 1g) exhibited the highest Papp (apparent permeability) value compared to the parent compound. The study reveals that menthol prodrugs exhibit stability at a pH of 5.8 and possess sufficient in vitro permeability values as preformulation parameters. Full article
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20 pages, 1057 KiB  
Article
Synthesis and Antimalarial Evaluation of New 1,3,5-tris[(4-(Substituted-aminomethyl)phenyl)methyl]benzene Derivatives: A Novel Alternative Antiparasitic Scaffold
by Sandra Albenque-Rubio, Jean Guillon, Anita Cohen, Patrice Agnamey, Solène Savrimoutou, Stéphane Moreau, Jean-Louis Mergny, Luisa Ronga, Ioannis Kanavos, Serge Moukha, Pascale Dozolme and Pascal Sonnet
Drugs Drug Candidates 2023, 2(3), 653-672; https://doi.org/10.3390/ddc2030033 - 08 Aug 2023
Viewed by 1145
Abstract
A series of new 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene compounds were designed, synthesized, and evaluated in vitro against two parasites (Plasmodium falciparum and Leishmania donovani). The biological results showed antimalarial activity with IC50 values in the sub and μM range. The in [...] Read more.
A series of new 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene compounds were designed, synthesized, and evaluated in vitro against two parasites (Plasmodium falciparum and Leishmania donovani). The biological results showed antimalarial activity with IC50 values in the sub and μM range. The in vitro cytotoxicity of these new aza polyaromatic derivatives was also evaluated on human HepG2 cells. The 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene 1m was found as one of the most potent and promising antimalarial candidates with a ratio of cytotoxic to antiprotozoal activities of 83.67 against the P. falciparum CQ-sensitive strain 3D7. In addition, derivative 1r was also identified as the most interesting antimalarial compound with a selectivity index (SI) of 17.28 on the W2 P. falciparum CQ-resistant strain. It was previously described that the telomeres of P. falciparum could be considered as potential targets of these kinds of aza heterocycles; thus, the ability of these new derivatives to stabilize the parasitic telomeric G-quadruplexes was measured through a FRET melting assay. Full article
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29 pages, 2809 KiB  
Review
Inhibitors of Farnesyl Diphosphate Synthase and Squalene Synthase: Potential Source for Anti-Trypanosomatidae Drug Discovery
by Boniface Pone Kamdem and Fabrice Fekam Boyom
Drugs Drug Candidates 2023, 2(3), 624-652; https://doi.org/10.3390/ddc2030032 - 04 Aug 2023
Viewed by 1354
Abstract
Trypanosomatids are mainly responsible for leishmaniasis, sleeping sickness, and Chagas disease, which are the most challenging among the neglected tropical diseases due to the problem of drug resistance. Although problems of target deconvolution and polypharmacology are encountered, a target-based approach is a rational [...] Read more.
Trypanosomatids are mainly responsible for leishmaniasis, sleeping sickness, and Chagas disease, which are the most challenging among the neglected tropical diseases due to the problem of drug resistance. Although problems of target deconvolution and polypharmacology are encountered, a target-based approach is a rational method for screening drug candidates targeting a biomolecule that causes infections. The present study aims to summarize the latest information regarding potential inhibitors of squalene synthase and farnesyl phosphate synthase with anti-Trypanosomatidae activity. The information was obtained by referencing textbooks and major scientific databases from their inception until April 2023. Based on in vitro experiments, more than seventy compounds were reported to inhibit squalene synthase and farnesyl diphosphate synthase. Among these compounds, more than 30 were found to be active in vitro against Trypanosomatidae, inferring that these compounds can be used as scaffolds to develop new drugs against trypanosomatid-related infections. Overall, natural and synthetic products can inhibit enzymes that are crucial for the survival and virulence of trypanosomatids. Moreover, in vitro experiments have confirmed the activity of more than half of these inhibitors using cell-based assays. Nevertheless, additional studies on the cytotoxicity, pharmacokinetics, and lead optimization of potent anti-Trypanosomatid compounds should be investigated. Full article
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9 pages, 614 KiB  
Article
In Vitro Evaluation of Arylsulfonamide Derivatives against Trypanosoma cruzi
by Policarpo Ademar Sales Junior, Silvane Maria Fonseca Murta and Jason Guy Taylor
Drugs Drug Candidates 2023, 2(2), 477-485; https://doi.org/10.3390/ddc2020024 - 08 Jun 2023
Viewed by 979
Abstract
Chagas disease is caused by the parasite protozoan Trypanosoma cruzi (T. cruzi) and affects millions of people in over 21 countries in around the world. The main forms of treatment of this disease, benznidazole and nifurtimox, present low cure rates in [...] Read more.
Chagas disease is caused by the parasite protozoan Trypanosoma cruzi (T. cruzi) and affects millions of people in over 21 countries in around the world. The main forms of treatment of this disease, benznidazole and nifurtimox, present low cure rates in the chronic phase and often have serious side effects. Herein, we describe the evaluation of the trypanocidal activity of arylsulfonamides. The arylsulfonamides were evaluated in vitro against the amastigote and trypomastigote forms of the parasite. An enantiomerically pure example of arylsulfonamide was also tested. The initial results suggest that the arylsulfonamides evaluated act as DNA binding agents. A moderate activity was monitored against the intracellular forms of T. cruzi, with the best compound exhibiting an IC50 value at 22 μM and a selectivity index of 120. However, the level of activity was not favorable for progressing towards in vivo studies for Chagas disease. Full article
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2022

Jump to: 2024, 2023

13 pages, 1254 KiB  
Article
Synthesis, Characterization, and Activity of Hydroxymethylnitrofurazone Nanocrystals against Trypanosoma cruzi and Leishmania spp.
by Cauê Benito Scarim, Aline de Souza, Débora Soares Souza Marins, Elda Gonçalves dos Santos, Lívia de Figueiredo Diniz Castro, Ivo Santana Caldas, Patrícia Ferreira Espuri, Marcos José Marques, Elizabeth Igne Ferreira, Nadia Araci Bou-Chacra and Chung Man Chin
Drugs Drug Candidates 2022, 1(1), 43-55; https://doi.org/10.3390/ddc1010005 - 13 Dec 2022
Viewed by 1504
Abstract
Hydroxymethylnitrofurazone (NFOH) is a prodrug of nitrofurazone devoid of mutagenic toxicity, with in vitro and in vivo activity against Trypanosoma cruzi (T. cruzi) and in vitro activity against Leishmania. In this study, we aimed to increase the solubility of [...] Read more.
Hydroxymethylnitrofurazone (NFOH) is a prodrug of nitrofurazone devoid of mutagenic toxicity, with in vitro and in vivo activity against Trypanosoma cruzi (T. cruzi) and in vitro activity against Leishmania. In this study, we aimed to increase the solubility of NFOH to improve its efficacy against T. cruzi (Chagas disease) and Leishmania species (Leishmaniasis) highly. Two formulations of NFOH nanocrystals (NFOH-F1 and NFOH-F2) were prepared and characterized by determining their particle sizes, size distribution, morphologies, crystal properties, and anti-trypanosomatid activities. Furthermore, cytotoxicity assays were performed. The results showed that the optimized particle size of 108.2 ± 0.8 nm (NFOH-F1) and 132.4 ± 2.3 nm (NFOH-F2) increased the saturation solubility and dissolution rate of the nanocrystals. These formulations exhibited moderate anti-Leishmania effects (Leishmania amazonensis) in vitro and potent in vitro activity against T. cruzi parasites (Y strain). Moreover, both formulations could reduce parasitemia (around 89–95% during the parasitemic peak) in a short animal model trial (Y strain from T. cruzi). These results suggested that the increased water solubility of the NFOH nanocrystals improved their activity against Chagas disease in both in vitro and in vivo assays. Full article
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