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Advances in Therapeutics against Eukaryotic Pathogens
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Advances in Therapeutics against Eukaryotic Pathogens

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 July 2024 | Viewed by 2856

Special Issue Editor

Dr. Edward L. D'Antonio

E-Mail Website
Guest Editor
Department of Natural Sciences, University of South Carolina Beaufort, Bluffton, SC 29909, USA
Interests: structural biology; biochemistry; Chagas disease; leishmaniasis; neglected tropical diseases; medicinal chemistry

Special Issue Information

Dear Colleagues,

Eukaryotic pathogens are responsible for devastating diseases across the world, and, coupled with that, physicians are limited regarding their use of administering efficacious, tolerable, and non-toxic therapeutic options to patients in need. Moreover, given the lack of vaccinations for such diseases, or even the disposition of drug resistance, humankind heavily depends on anti-parasitic drugs. It is often observed that chemical therapeutics with biological activity against one pathogen may also be effective against another, or others. Thus, this Special Issue aims to identify recent advances from therapeutic drug compounds against eukaryotic microorganisms that cause human disease, which will be showcased and discussed. Submissions of experimental or simulated medicinal chemistry research that focus on the development of either known therapeutics and/or the discovery of novel compounds will be of high priority. Since Int. J. Mol. Sci. is dedicated to chemistry and biology at the molecular level, pure clinical studies will not be considered, but clinical submissions with biomolecular experiments are certainly welcomed.

Dr. Edward L. D'Antonio
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • medicinal chemistry
  • parasitology
  • pathogen
  • drug-target
  • NTD
  • cryptosporidia
  • Giardia
  • helminths
  • Leishmania
  • Naegleria
  • Plasmodium
  • Schistosoma
  • Toxoplasma
  • Trichomonas
  • Trypanosoma
 

Published Papers (2 papers)

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Research

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17 pages, 3277 KiB  
Article
Discovery of Strong 3-Nitro-2-Phenyl-2H-Chromene Analogues as Antitrypanosomal Agents and Inhibitors of Trypanosoma cruzi Glucokinase
by Shane M. Carey, Destiny M. O’Neill, Garrett B. Conner, Julian Sherman, Ana Rodriguez and Edward L. D’Antonio
Int. J. Mol. Sci. 2024, 25(8), 4319; https://doi.org/10.3390/ijms25084319 - 13 Apr 2024
Viewed by 686
Abstract
Chagas disease is one of the world’s neglected tropical diseases, caused by the human pathogenic protozoan parasite Trypanosoma cruzi. There is currently a lack of effective and tolerable clinically available therapeutics to treat this life-threatening illness and the discovery of modern alternative [...] Read more.
Chagas disease is one of the world’s neglected tropical diseases, caused by the human pathogenic protozoan parasite Trypanosoma cruzi. There is currently a lack of effective and tolerable clinically available therapeutics to treat this life-threatening illness and the discovery of modern alternative options is an urgent matter. T. cruzi glucokinase (TcGlcK) is a potential drug target because its product, d-glucose-6-phosphate, serves as a key metabolite in the pentose phosphate pathway, glycolysis, and gluconeogenesis. In 2019, we identified a novel cluster of TcGlcK inhibitors that also exhibited anti-T. cruzi efficacy called the 3-nitro-2-phenyl-2H-chromene analogues. This was achieved by performing a target-based high-throughput screening (HTS) campaign of 13,040 compounds. The selection criteria were based on first determining which compounds strongly inhibited TcGlcK in a primary screen, followed by establishing on-target confirmed hits from a confirmatory assay. Compounds that exhibited notable in vitro trypanocidal activity over the T. cruzi infective form (trypomastigotes and intracellular amastigotes) co-cultured in NIH-3T3 mammalian host cells, as well as having revealed low NIH-3T3 cytotoxicity, were further considered. Compounds GLK2-003 and GLK2-004 were determined to inhibit TcGlcK quite well with IC50 values of 6.1 µM and 4.8 µM, respectively. Illuminated by these findings, we herein screened a small compound library consisting of thirteen commercially available 3-nitro-2-phenyl-2H-chromene analogues, two of which were GLK2-003 and GLK2-004 (compounds 1 and 9, respectively). Twelve of these compounds had a one-point change from the chemical structure of GLK2-003. The analogues were run through a similar primary screening and confirmatory assay protocol to our previous HTS campaign. Subsequently, three in vitro biological assays were performed where compounds were screened against (a) T. cruzi (Tulahuen strain) infective form co-cultured within NIH-3T3 cells, (b) T. brucei brucei (427 strain) bloodstream form, and (c) NIH-3T3 host cells alone. We report on the TcGlcK inhibitor constant determinations, mode of enzyme inhibition, in vitro antitrypanosomal IC50 determinations, and an assessment of structure–activity relationships. Our results reveal that the 3-nitro-2-phenyl-2H-chromene scaffold holds promise and can be further optimized for both Chagas disease and human African trypanosomiasis early-stage drug discovery research. Full article
(This article belongs to the Special Issue Advances in Therapeutics against Eukaryotic Pathogens)
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Review

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12 pages, 979 KiB  
Review
Microscopic Menaces: The Impact of Mites on Human Health
by Christina Linn, Andrea O’Malley, Kriti Khatri, Elaine M. Wright, Dylan Sebagh, Miodrag Grbić, Krzysztof Kowal and Maksymilian Chruszcz
Int. J. Mol. Sci. 2024, 25(7), 3675; https://doi.org/10.3390/ijms25073675 - 26 Mar 2024
Viewed by 839
Abstract
Mites are highly prevalent arthropods that infest diverse ecological niches globally. Approximately 55,000 species of mites have been identified but many more are yet to be discovered. Of the ones we do know about, most go unnoticed by humans and animals. However, there [...] Read more.
Mites are highly prevalent arthropods that infest diverse ecological niches globally. Approximately 55,000 species of mites have been identified but many more are yet to be discovered. Of the ones we do know about, most go unnoticed by humans and animals. However, there are several species from the Acariformes superorder that exert a significant impact on global human health. House dust mites are a major source of inhaled allergens, affecting 10–20% of the world’s population; storage mites also cause a significant allergy in susceptible individuals; chiggers are the sole vectors for the bacterium that causes scrub typhus; Demodex mites are part of the normal microfauna of humans and their pets, but under certain conditions populations grow out of control and affect the integrity of the integumentary system; and scabies mites cause one of the most common dermatological diseases worldwide. On the other hand, recent genome sequences of mites provide novel tools for mite control and the development of new biomaterial with applications in biomedicine. Despite the palpable disease burden, mites remain understudied in parasitological research. By better understanding mite biology and disease processes, researchers can identify new ways to diagnose, manage, and prevent common mite-induced afflictions. This knowledge can lead to improved clinical outcomes and reduced disease burden from these remarkably widespread yet understudied creatures. Full article
(This article belongs to the Special Issue Advances in Therapeutics against Eukaryotic Pathogens)
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