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Drug Design Against Neglected Tropical Diseases

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

Deadline for manuscript submissions: closed (30 March 2021) | Viewed by 3019

Special Issue Editors


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Guest Editor
Graduate Programme in Genomic Science and Biotechnology, Catholic University of Brasília, Taguatinga, Brasília, Brazil
Interests: fungal infection; biotechnology; recombinant protein; genomic; antifungals

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Guest Editor
Department of Clinical Analysis and Biomedicine, Laboratory of Medical Mycology, State University of Maringá, Maringá, Paraná, Brazil
Interests: fungal infection; antifungals; biotechnology; recombinant protein; bioinformatics; drug design

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Guest Editor
LORIA Institute (Laboratoire Lorrain de Recherches en Informatique et Applications), Université de Lorraine, CNRS, INRIA, Vandoeuvre les Nancy, France
Interests: virtual screening; molecular dynamics; Monte Carlo; QM/MM; molecular recognition; optimization; data mining; clustering; deep learning
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neglected tropical diseases are a major public health problem in tropical and subtropical countries. According to the WHO, they affect one billion people, and the costs for developing economies are in the range of billions of dollars each year. Advances in the frontier areas of knowledge, such as genomics, proteomics, and bioinformatics, have opened up new perspectives regarding the design of new therapeutic options, especially for diseases for which investment is restricted.
Thus, this Special Issues aims to discuss the state-of-the-art methodologies being used in drug design as well as their challenges and perspectives. In addition, it will review the literature regarding diseases whose studies are most advanced and whether models developed for those diseases can be applied to other diseases.

Prof. Dr. Maria Sueli Soares Felipe
Prof. Dr. Erika Seki Kioshima Cotica
Dr. Bernard Maigret
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 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

  • neglected tropical diseases
  • drug design
  • drug repositioning
  • in silico approaches
  • drug targets

Published Papers (1 paper)

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Research

21 pages, 9467 KiB  
Article
Optimization of 1,4-Naphthoquinone Hit Compound: A Computational, Phenotypic, and In Vivo Screening against Trypanosoma cruzi
by Leonardo S. Lara, Guilherme C. Lechuga, Caroline dos S. Moreira, Thaís B. Santos, Vitor F. Ferreira, David R. da Rocha and Mirian C. S. Pereira
Molecules 2021, 26(2), 423; https://doi.org/10.3390/molecules26020423 - 15 Jan 2021
Cited by 10 | Viewed by 2423
Abstract
Chagas disease (CD) still represents a serious public health problem in Latin America, even after more than 100 years of its discovery. Clinical treatments (nifurtimox and benznidazole) are considered inadequate, especially because of undesirable side effects and low efficacy in the chronic stages [...] Read more.
Chagas disease (CD) still represents a serious public health problem in Latin America, even after more than 100 years of its discovery. Clinical treatments (nifurtimox and benznidazole) are considered inadequate, especially because of undesirable side effects and low efficacy in the chronic stages of the disease, highlighting the urgency for discovering new effective and safe drugs. A small library of compounds (1ai and 2aj) was designed based on the structural optimization of a Hit compound derived from 1,4-naphthoquinones (C2) previously identified. The biological activity, structure-activity relationship (SAR), and the in silico physicochemical profiles of the naphthoquinone derivatives were analyzed. Most modifications resulted in increased trypanocidal activity but some substitutions also increased toxicity. The data reinforce the importance of the chlorine atom in the thiophenol benzene ring for trypanocidal activity, highlighting 1g, which exhibit a drug-likeness profile, as a promising compound against Trypanosoma cruzi. SAR analysis also revealed 1g as cliff generator in the structure-activity similarity map (SAS maps). However, compounds C2 and 1g were unable to reduce parasite load, and did not prevent mouse mortality in T. cruzi acute infection. Phenotypic screening and computational analysis have provided relevant information to advance the optimization and design of new 1,4-naphthoquinone derivatives with a better pharmacological profile. Full article
(This article belongs to the Special Issue Drug Design Against Neglected Tropical Diseases)
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