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Pharmaceutics
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Advances in Antiparasitic Agents
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Advances in Antiparasitic Agents

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 24 May 2026 | Viewed by 4586

Special Issue Editor

Prof. Dr. Juan José García-Rodríguez

E-Mail Website
Guest Editor
Department of Parasitology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Interests: parasitology; helminths; immunology; immunomodulation; parasite immunomodulation

Special Issue Information

Dear Colleagues,

The development of new antiparasitic drugs is crucial for global health, particularly in tropical and subtropical regions where parasitic infections are prevalent. Parasitic diseases, such as malaria, leishmaniasis, and schistosomiasis, affect millions of people annually, leading to significant morbidity and mortality. Traditional treatments are increasingly compromised by the emergence of drug-resistant parasites, making it necessary to discover and develop new therapeutic agents.

Research into new antiparasitic drugs involves a multidisciplinary approach, incorporating advances in genomics, bioinformatics, and molecular biology. Genomic studies enable the identification of novel drug targets by elucidating the genetic makeup and metabolic pathways of parasites. These targets can be exploited to design specific inhibitors that disrupt a parasite’s life cycle without harming a host. High-throughput screening methods, coupled with bioinformatics tools, facilitate the rapid identification of potential drug candidates from vast chemical libraries.

In addition, the development of antiparasitic drugs benefits from advances in drug delivery systems. Nanotechnology, for instance, offers innovative solutions for enhancing drug bioavailability and targeting specific tissues, thereby increasing therapeutic efficacy and reducing side effects. The integration of these technologies into antiparasitic drug research promises more effective treatments with improved safety profiles.

In conclusion, ongoing research into new antiparasitic drugs is of vital importance to combat the global burden of parasitic diseases. By addressing the challenges of drug resistance and improving drug delivery mechanisms, researchers can develop innovative therapies that save lives and improve the quality of life of millions of individuals affected by parasitic infections.

This Special Issue invites contributions covering the most recent advances in both the development of new antiparasitic drugs and in studies on the modifications of or synergies between molecules that contribute to an increase in the efficacy or safety of existing drugs. We encourage the submission of original and review articles showing advances in pharmaceutical technology, pharmacokinetics, metabolism, pharmacology, both in vitro and in vivo experiments, and in silico modeling as well as simulation approaches.

I look forward to receiving your contributions.

Prof. Dr. Juan José García-Rodríguez
Guest 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 special issue 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. Pharmaceutics is an international peer-reviewed open access monthly 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 2900 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

  • parasites
  • parasitic diseases
  • drug combinations
  • antiparasitic activity
  • pharmacokinetics
  • drug resistance
  • mechanism of action
  • formulations
  • drug synthesis and discovery

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Published Papers (4 papers)

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Research

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18 pages, 2097 KB  
Article
Use of Metabolomics Approach in the Discovery of Active Compounds from Macroalgae Laurencia Species Against Schistosomiasis
by Amanda Beatriz Silva Soares, Patricia Aoki Miyasato, Rafaela Paula de Freitas, Adolfo Luis Almeida Maleski, Daniel Carvalho Pimenta, Pio Colepicolo, Erika Mattos Stein, Arthur Ladeira Macedo, Carlos Alexandre Carollo and Eliana Nakano
Pharmaceutics 2025, 17(10), 1294; https://doi.org/10.3390/pharmaceutics17101294 - 2 Oct 2025
Viewed by 539
Abstract
Background: Marine macroalgae has been studied by our research group as alternative sources of bioactive compounds with promising antiparasitic activity, particularly against Schistosoma mansoni. Objectives: This study aimed to employ a metabolomics-based approach to identify anthelminthic active compounds from the macroalgae [...] Read more.
Background: Marine macroalgae has been studied by our research group as alternative sources of bioactive compounds with promising antiparasitic activity, particularly against Schistosoma mansoni. Objectives: This study aimed to employ a metabolomics-based approach to identify anthelminthic active compounds from the macroalgae Laurencia aldingensis Saito and Womersley 1974 and Laurencia dendroidea J. Agardh 1852. Methods: The algae were extracted using a dichloromethane/methanol mixture, followed by liquid–liquid partitioning and sequential chromatographic fractionation using solvents of varying polarities. The resulting fractions were tested for biological activity against adult Schistosoma mansoni worms. Detailed chemical characterization of the extracts was conducted via HPLC-DAD-MS/MS, with subsequent data alignment and statistical analysis (Pearson correlation) to associate specific chemical compounds with the observed bioactivity. Results: Non-polar fractions (hexane and dichloromethane) exhibited significant anthelminthic activity, substantially reducing parasite viability and reproduction. Specific subfractions obtained from the dichloromethane fraction demonstrated notable activity. Metabolomic analysis revealed considerable chemical diversity, emphasizing the presence of bromophenols and halogenated sesquiterpenes, including potentially novel compounds with therapeutic potential against schistosomiasis. Conclusions: The metabolomics approach proved effective in identifying promising bioactive compounds from Laurencia spp. macroalgae with activity against S. mansoni. Full article
(This article belongs to the Special Issue Advances in Antiparasitic Agents)
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20 pages, 4017 KB  
Article
Design, Synthesis, In Vitro and In Silico Biological Evaluation of New Pyridine-2,5-Dicarboxylates Esters Bearing Natural Source Fragments as Anti-Trypanosomatid Agents
by Luis M. Sánchez-Palestino, Adriana Moreno-Rodríguez, Diana V. Navarrete-Carriola, Marlet Martínez-Archundia, Marhian López-Vargas, Liliana Argueta-Figueroa, Lenci K. Vázquez-Jiménez, Alma D. Paz-González, Eyra Ortiz-Pérez, Michael P. Doyle and Gildardo Rivera
Pharmaceutics 2025, 17(10), 1271; https://doi.org/10.3390/pharmaceutics17101271 - 28 Sep 2025
Viewed by 797
Abstract
Background: Chagas disease and leishmaniasis remain public health concerns. Despite the existence of approved medications for the treatment of these diseases, most patients discontinue treatment due to long drug regimens and/or the severe side effects of these drugs. This leads to treatment [...] Read more.
Background: Chagas disease and leishmaniasis remain public health concerns. Despite the existence of approved medications for the treatment of these diseases, most patients discontinue treatment due to long drug regimens and/or the severe side effects of these drugs. This leads to treatment failure and potential future drug resistance. Therefore, the search for new molecules with trypanocidal activity, low cytotoxicity, and high selectivity is essential to address this challenge. Methods: In this work, three series (a, b, and c) of pyridine-2,5-dicarboxylate esters were synthesized using different β-keto-esters bearing naturally occurring fragments and 1,2,3-triazine-1-oxides via the inverse electron demand Diels–Alder (IEDDA) reaction. The structural elucidation of the compounds was performed using NMR (1H and 13C) and HRMS, and the crystal structure of compound 6a was also obtained. Furthermore, a biological assay was performed for all synthesized and characterized compounds to determine their cytotoxicity against Trypanosoma cruzi, Leishmania mexicana, and the J774.2 macrophage cell line. Finally, the in silico determination of their pharmacokinetic and toxicological properties was performed using the SwissADME and ProTox 3.0 platforms. Results: Compounds 3a, 4a, 5a, 4b, and 8c had the highest anti-Trypanosoma cruzi activity against both strains (IC50 ≤ 56.68 µM). Compounds 8b, 10a, 9b, and 12b had considerable leishmanicidal activity against Leishmania mexicana against both strains (IC50 ≤ 161.53 µM). Furthermore, in silico prediction of ADMET properties suggest that these pyridine compounds possess good pharmacokinetic profile. The results are also consistent with low in vitro cytotoxicity and high selectivity. Conclusions: The synthesized pyridine-2,5-dicarboxylate esters have promising activity against Trypanosoma cruzi and Leishmania mexicana, with low cytotoxicity and good drug-like properties, suggesting that these compounds are potential candidates for further evaluation as new treatments for Chagas disease and leishmaniasis. Full article
(This article belongs to the Special Issue Advances in Antiparasitic Agents)
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15 pages, 2319 KB  
Article
Nifuroxazide and 4-Hydroxybenzhydrazone Derivatives as New Antiparasitic (Trypanosoma cruzi and Leishmania mexicana) and Anti-Mycobacterium tuberculosis Agents
by Timoteo Delgado-Maldonado, Diana V. Navarrete-Carriola, Lenci K. Vázquez-Jiménez, Alma D. Paz-González, Baojie Wan, Scott Franzblau, Othman Mueen Mohammed, Lorena Rodríguez-Páez, Charmina Aguirre-Alvarado, Verónica Alcántara-Farfán, Joaquín Cordero-Martínez, Debasish Bandyopadhyay, Adriana Moreno-Rodríguez and Gildardo Rivera
Pharmaceutics 2025, 17(5), 621; https://doi.org/10.3390/pharmaceutics17050621 - 7 May 2025
Cited by 1 | Viewed by 1178
Abstract
Background/Objectives: Nifuroxazide (Nfz) is a drug that has been used as a scaffold for designing antimicrobial and antiparasitic agents. This study aimed to synthesize and evaluate in vitro of Nfz and twenty-five 4-hydroxybenzhydrazone derivatives as potential anti-Trypanosoma cruzi, anti-Leishmania mexicana [...] Read more.
Background/Objectives: Nifuroxazide (Nfz) is a drug that has been used as a scaffold for designing antimicrobial and antiparasitic agents. This study aimed to synthesize and evaluate in vitro of Nfz and twenty-five 4-hydroxybenzhydrazone derivatives as potential anti-Trypanosoma cruzi, anti-Leishmania mexicana, and anti-Mycobacterium tuberculosis agents. Methods: The compounds were synthesized by condensing 4-hydroxybenzhydrazide with appropriate aldehydes in acidic conditions and structurally confirmed by spectroscopic techniques. All compounds were evaluated in vitro against T. cruzi strains (NINOA and A1), L. mexicana (M379 and FCQEPS strains), and M. tuberculosis (H37Rv strain), followed by enzymatic assays against T. cruzi cysteine proteases. Results: Compound Nfz-24 (IC50 = 6.8 μM) had better trypanocidal activity than the reference drugs benznidazole (IC50 > 30 μM) and nifurtimox (IC50 > 7 μM) against the NINOA strain, and Nfz-8 (IC50 = 7.2 μM) was the compound most active against the A1 strain with a high inhibition of T. cruzi cysteine proteases (IC50 = 4.6 μM) and low cytotoxic effects (CC50 >100 μM). On the other hand, compound Nfz-5 (IC50 = 5.2 μM) had a 25-fold better leishmanicidal effect than glucantime (IC50 > 125 μM) against the L. mexicana M379 strain, and compound Nfz-13 had the best leishmanicidal effects (IC50 = 10.2 μM) against the FCQEPS strain. Finally, Nfz, Nfz-1, and Nfz-2 had minimum inhibitory concentration (MIC) values of 12.3, 5.1, and 18.8 μg/mL against M. tuberculosis, respectively. Conclusions: In summary, these results suggest that the compounds Nfz-1, Nfz-2, Nfz-5, Nfz-8, Nfz-10, Nfz-15, Nfz-24, and Nfz-25 are candidates for further studies to develop new and more potent anti-T. cruzi, anti-leishmaniasis, and anti-M. tuberculosis agents. Full article
(This article belongs to the Special Issue Advances in Antiparasitic Agents)
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Review

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50 pages, 2436 KB  
Review
Harnessing Phytonanotechnology to Tackle Neglected Parasitic Diseases: Focus on Chagas Disease and Malaria
by Manuela García, María S. Magi and Mónica C. García
Pharmaceutics 2025, 17(8), 1043; https://doi.org/10.3390/pharmaceutics17081043 - 12 Aug 2025
Viewed by 1095
Abstract
Neglected parasitic diseases such as Chagas disease and malaria continue to pose major public health challenges, particularly in low-resource settings. Current therapies are often limited by high toxicity, poor efficacy, drug resistance, and limited accessibility. Phytochemicals, naturally occurring compounds in plants, have played [...] Read more.
Neglected parasitic diseases such as Chagas disease and malaria continue to pose major public health challenges, particularly in low-resource settings. Current therapies are often limited by high toxicity, poor efficacy, drug resistance, and limited accessibility. Phytochemicals, naturally occurring compounds in plants, have played a crucial role in medicine since ancient times and have gained renewed attention for their demonstrated antiparasitic activity. However, many products of natural origin (PNOs) face significant barriers to clinical use, including poor solubility, low bioavailability, and chemical instability. These limitations have driven researchers to explore alternative and innovative approaches based on the use of PNOs to tackle these parasitic infections more effectively. This review provides a comprehensive overview of key PNOs with proven activity against Trypanosoma cruzi and Plasmodium spp., the causative agents of Chagas disease and malaria, respectively. Recent advances in the design of phytonanoformulations are analyzed and discussed, emphasizing the potential of nanocarrier-based systems incorporating PNOs as a strategy to improve the pharmacokinetic and therapeutic properties of these natural products. By critically examining the integration of phytochemicals into nanotechnology-based drug delivery platforms, this review highlights the promise of phytonanotechnology to overcome current limitations in antiparasitic therapy and support the development of more effective and accessible treatments for neglected parasitic diseases. Full article
(This article belongs to the Special Issue Advances in Antiparasitic Agents)
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