Human protozoan diseases represent a serious health problem worldwide, affecting mainly people in social and economic vulnerability. These diseases have attracted little investment in drug discovery, which is reflected in the limited available therapeutic arsenal. Authorized drugs present problems such as low efficacy in some stages of the disease or toxicity, which result in undesirable side effects and treatment abandonment. Moreover, the emergence of drug-resistant parasite strains makes necessary an even greater effort to develop safe and effective antiparasitic agents. Among the chemotypes investigated for parasitic diseases, the indole nucleus has emerged as a privileged molecular scaffold for the generation of new drug candidates. In this review, the authors provide an overview of the indole-based compounds developed against important parasitic diseases, namely malaria, trypanosomiasis and leishmaniasis, by focusing on the design, optimization and synthesis of the most relevant synthetic indole scaffolds recently reported.
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http://dx.doi.org/10.3390/molecules27010319 | DOI Listing |
RSC Adv
January 2025
The Organic Chemistry Research Laboratory (OCRL), Department of Chemistry, Faculty of Science, University of Zanjan Zanjan 45371-38791 Iran
In recent research, quinoline and indole structures have gained recognition for their significant clinical relevance and effectiveness. These compounds are known for their wide-ranging pharmacological effects, which include anticancer, antibacterial, antifungal, antiviral, and anti-inflammatory properties. Researchers have successfully implemented a variety of innovative synthetic strategies, leading to the creation of numerous compounds that display fascinating biological activities in diverse fields.
View Article and Find Full Text PDFACS Infect Dis
January 2025
Pharmaceutical Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani, Vidya Vihar 333031, (RJ) India.
Antimicrobial drug resistance is a significant global health challenge, causing hundreds of thousands of deaths annually and severely impacting healthcare systems worldwide. Several reported antimicrobial compounds have a guanidine motif, as the positive charge on guanidine promotes cell lysis. Therefore, pyrrole- and indole-based allylidene hydrazine carboximidamide derivatives with guanidine motifs are proposed as antimicrobial agents that mimic cationic antimicrobial peptides (CAMPs).
View Article and Find Full Text PDFAntioxidants (Basel)
December 2024
Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy.
Based on the established neuroprotective properties of indole-based compounds and their significant potential as multi-targeted therapeutic agents, a series of synthetic indole-phenolic compounds was evaluated as multifunctional neuroprotectors. Each compound demonstrated metal-chelating properties, particularly in sequestering copper ions, with quantitative analysis revealing approximately 40% chelating activity across all the compounds. In cellular models, these hybrid compounds exhibited strong antioxidant and cytoprotective effects, countering reactive oxygen species (ROS) generated by the Aβ(25-35) peptide and its oxidative byproduct, hydrogen peroxide, as demonstrated by quantitative analysis showing on average a 25% increase in cell viability and a reduction in ROS levels to basal states.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of Pharmaceutical Chemistry, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Belagavi 590 010, Karnataka, India.
Indole, a fundamental heterocyclic core, has emerged as a cornerstone in the medicinal chemistry due to its diverse biological activities and structural versatility. This aromatic compound, present in natural as well as synthetic compounds, offers a versatile platform for the drug discovery. By strategically incorporating functional groups or pharmacophores, researchers can tailor indole-derivatives to target a wide range of diseases.
View Article and Find Full Text PDFEur J Med Chem
February 2025
Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616, Nizwa, Oman. Electronic address:
In this present work, we describe the syntheses of a new series of 32 1H-indole-based-meldrum linked 1H-1,2,3-triazole derivatives (2-13, 15a-15f, 16a-16f, 17a-17f and 19a, 19b, 20a), which constitute a new class of 1H-1,2,3-triazoles. Compounds 15a-15f, 16a-16f, 17a-17f have been prepared by employing "click" reactions between substituted 1H-indole-based meldrum alkynes (11, 12 and 13) and substituted aromatic azides (14a-14f) in the presence of copper iodide (CuI) and Hünig's base. Then, the synthesis of compounds 19, 20 through decomposition of meldrum moiety.
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