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Novel Antiparasitic Molecules for Neglected Tropical Diseases

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 1286

Special Issue Editor


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Guest Editor
LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Interests: organic synthesis; fine chemistry; medicinal chemistry; pharmaceutical chemistry; drug development; porphyrin; photochemistry; photodynamic therapy; antimicrobial; ceramic materials; decarbonization; synthetic fuels
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Special Issue Information

Dear Colleagues,

Neglected tropical diseases (NTDs) are a group of parasitic infections affecting over a billion people in tropical and subtropical regions, primarily impacting impoverished communities. These diseases are caused by a variety of pathogens, including protozoa, helminths, and ectoparasites. Prominent examples include Chagas disease, human African trypanosomiasis, schistosomiasis, filariasis, and leishmaniasis. Together, NTDs affect more than one billion people globally, exerting a profound impact on public health, economic development, and social well-being in endemic communities. Despite progress having been made, these diseases remain underfunded and under-researched. Many current therapies suffer from high toxicity, limited efficacy, growing drug resistance, and impractical treatment regimens that hinder control efforts in endemic settings.

This Special Issue invites original research papers and comprehensive reviews that explore the discovery, design, and development of new antiparasitic molecules with potential application against neglected tropical diseases. Contributions may include studies on natural products, synthetic organic compounds, metal-based drugs, hybrid molecules, or repurposed drugs. Topics of interest include but are not limited to the following: molecular targets, structure–activity relationships, in vitro and in vivo activity, mechanisms of action, and innovative delivery systems. Research that bridges the gap between molecular innovation and therapeutic application is especially encouraged.

Dr. Carlos Monteiro
Guest Editor

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Keywords

  • neglected tropical diseases
  • antiparasitic agents
  • drug design and discovery
  • structure–activity relationships
  • drug resistance

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Published Papers (2 papers)

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Research

18 pages, 3615 KB  
Article
Using the Scaffold of FDA-Approved Drugs with Trypanocidal Activity to Identify New Anti-Trypanosoma cruzi Agents: An In Silico and In Vitro Approach
by Lenci K. Vázquez-Jiménez, Alonzo González-González, Timoteo Delgado-Maldonado, Rogelio Gómez-Escobedo, Guadalupe Avalos-Navarro, Adriana Moreno-Rodríguez, Alma D. Paz-González, Eyra Ortiz-Pérez, Benjamín Nogueda-Torres and Gildardo Rivera
Molecules 2026, 31(8), 1327; https://doi.org/10.3390/molecules31081327 - 17 Apr 2026
Viewed by 352
Abstract
Chagas disease affects millions of people worldwide, including those in Latin America. The only drugs available for its treatment are benznidazole and nifurtimox. However, these drugs present high toxicity and limited efficacy. Therefore, the search for new treatments continues. In this regard, computer-assisted [...] Read more.
Chagas disease affects millions of people worldwide, including those in Latin America. The only drugs available for its treatment are benznidazole and nifurtimox. However, these drugs present high toxicity and limited efficacy. Therefore, the search for new treatments continues. In this regard, computer-assisted drug design has been implemented in scientific research for drug repurposing, allowing for reduced costs and time. Therefore, the objective of this work was to search for analogs of FDA-approved drugs with activity against Trypanosoma cruzi through ligand-based virtual screening and their biological evaluation against blood trypomastigotes. The compound TD-095 (LC50 = 48.60 and 13.75 µM), a ketanserin analogue, TS-936 (LC50 = 71.55 and 37.54 µM), a terfenadine analogue, and TD-831 (LC50 = 75.94 and 26.17 µM), a sulfasalazine analogue, were considered as potential trans-sialidase inhibitors; TIM-967 (LC50 = 69.70 and 39.69 µM) and LK-284 (LC50 = 116.7 and 82.29 µM), two sulfonylurea analogues, were considered as potential triosephosphate isomerase inhibitors, showing better trypanocidal activity against NINOA and INC-5 strains, respectively, than the reference drugs. Molecular dynamics simulations predicted the stability of the compounds in complex with their respective proteins. Finally, the ADMET predictive analysis showed favorable properties for the compounds. These results support continued research into new agents against Trypanosoma cruzi, using structures of drugs already approved by the FDA. Full article
(This article belongs to the Special Issue Novel Antiparasitic Molecules for Neglected Tropical Diseases)
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18 pages, 9609 KB  
Article
An In Silico and In Vitro Approach Identified Potential Trypanothione Synthetase Inhibitors with Trypanocidal Activity
by Rogelio Gómez-Escobedo, Domingo Méndez-Álvarez, Alma D. Paz-González, Eyra Ortiz-Pérez, Lenci K. Vázquez-Jiménez, Ana Verónica Martínez-Vázquez, Timoteo Delgado-Maldonado, José M. Quintero-Solano, Citlali Vázquez, Emma Saavedra, Guadalupe Avalos-Navarro, Karina Vázquez, Gildardo Rivera and Benjamín Nogueda-Torres
Molecules 2026, 31(7), 1139; https://doi.org/10.3390/molecules31071139 - 30 Mar 2026
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Abstract
In this study, a drug repurposing strategy was implemented with the aim of identifying new trypanocidal agents against Trypanosoma cruzi (T. cruzi). A total of 924 Food and Drug Administration (FDA)-approved drugs were screened by molecular docking on three sites of [...] Read more.
In this study, a drug repurposing strategy was implemented with the aim of identifying new trypanocidal agents against Trypanosoma cruzi (T. cruzi). A total of 924 Food and Drug Administration (FDA)-approved drugs were screened by molecular docking on three sites of trypanothione synthetase (TS), including the catalytic site, a blind docking site, and a potential allosteric site. Selected compounds were further evaluated through in vitro and in vivo assays. Tadalafil, Zafirlukast, Raltegravir, and Olmesartan had better trypanocidal activity than the reference drugs Benznidazole and Nifurtimox in the in vitro evaluation against the trypomastigote form. Additionally, these drugs were able to decrease parasitemia by 20–50% in mice in an acute treatment. Molecular dynamics simulations (MDS) at 120 ns helped link findings from in vitro/in vivo experiments to a potential mechanism of action targeting T. cruzi trypanothione synthetase (TcTS). Therefore, the results encourage the use of these drugs to develop new anti-T. cruzi agents. Full article
(This article belongs to the Special Issue Novel Antiparasitic Molecules for Neglected Tropical Diseases)
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