AI Article Synopsis
- * Researchers have created a library of imidazo-fused heterocycles and found that imidazo-pyrimidine is particularly effective against leishmanial forms, showing an IC value of 6.63 μM, which is about twice as potent as the standard drug miltefosine.
- * The imidazo-pyrimidine compound demonstrates strong selective activity against the parasites while being over 10 times more harmful to the parasites compared to human cells, suggesting it could be a promising candidate for new leishman
Article Abstract
Leishmania poses a substantial threat to the human population all over the globe because of its visceral and cutaneous spread engendered by all 20 species. Unfortunately, the available drugs against leishmania are already hobbled with toxicity, prolonged treatment, and increasing instances of acquirement of resistance. Under these grave circumstances, the development of new drugs has become imperative to keep these harmful microbes at bay. To this end, a Groebke-Blackburn-Bienaymé multicomponent reaction-based library of different imidazo-fused heterocycles has been synthesized and screened against promastigotes and amastigotes. Among the library compounds, the imidazo-pyrimidine has been found to be the most effective (inhibitory concentration of 50% (IC) < 10 μM), with selective antileishmanial activity on amastigote forms, a stage of the parasite related to human disease. The compound has exhibited an IC value of 6.63 μM, being ∼two times more active than miltefosine, a reference drug. Furthermore, this compound is >10 times more destructive to the intracellular parasites than host cells. The observed in vitro antileishmanial activity along with suitable in silico physicochemical and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of compound reinforce the imidazo-pyrimidine scaffold as a new antileishmanial pharmacophore and encourage further murine experimental leishmaniasis studies.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621021 | PMC |
| http://dx.doi.org/10.1021/acsomega.3c05441 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis and biological evaluation of 4,7,9-trisubstituted benzoxazepines as antileishmanial agents.
Bioorg Med Chem Lett
December 2024
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0509 USA. Electronic address:
Herein we report a series of antileishmanial analogues derived from 4-[(3,5-dimethyl-4-isoxazolyl)acetyl]-9-[(1-methyl-3-piperidinyl)methoxy]-7-(5-methyl-2-thienyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine (1), which was identified through a previously reported high-throughput phenotypic screen. The analogue series was designed, synthesized, and evaluated for antileishmanial activity to establish pharmacophore elements and preliminary structure-activity relationships as key steps in validating the series for further optimization. This study led to identification of the early lead compound 46, which exhibited sub-micromolar proliferation inhibitory activity against intra-macrophage L.
View Article and Find Full Text PDFIdentification of Novel Antileishmanial Chemotypes By High-Throughput Virtual and In Vitro Screening.
Acta Parasitol
September 2024
Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan, Pakistan.
Background: Leishmaniasis is a deadly protozoan parasitic disease and a significant health problem in underdeveloped and developing countries. The global spread of the parasite, coupled with the emergence of drug resistance and severe side effects associated with existing treatments, has necessitated the identification of new and potential drugs.
Objective: This study aimed to identify promising compounds for the treatment of leishmaniasis by targeting two essential enzymes of Leishmania donovani: trypanothione reductase (Try-R) and trypanothione synthetase (Try-S).
Synthesis, biological activities, and structure-activity relationships of Morita-Baylis-Hillman adducts: An update.
Arch Pharm (Weinheim)
October 2024
Department of Chemistry, GLA University, Mathura, Uttar Pradesh, India.
The Morita-Baylis-Hillman (MBH) reaction is a unique C-C bond-forming technique for the generation of multifunctional allylic alcohols (MBH adducts) in a single operation. In recent years, these MBH adducts have emerged as a novel class of compounds with significant biological potential, including anticancer, anti-leishmanial, antibacterial, antifungal, anti-herbicidal effects and activity against Chagas disease, and so on. The aim of this review is to assimilate the literature findings from 2011 onwards related to the synthesis and biological potential of MBH adducts, with an emphasis on their structure-activity relationships (SAR).
View Article and Find Full Text PDF1,3,5-Triazine: Recent Development in Synthesis of its Analogs and Biological Profile.
Mini Rev Med Chem
October 2024
Department of Chemistry, Banasthali Vidyapith, Banasthali-304022, India.
Triazine is an important pharmacophore in the field of research for the development of novel medications due to its presence in numerous powerful physiologically active compounds with significant medical potential, such as anti-tumor, anti-viral, anti-inflammatory, anti-microbial, anti- HIV, anti-leishmanial and others. The easy availability of triazine, high reactivity, simple synthesis of their analog, and their notable broad range of biological activities have garnered chemist interest in designing s-triazine-based drugs. The interest of medicinal chemists has been sparked by the structure-activity relationship of these biologically active entities, leading to the discovery of several promising lead molecules.
View Article and Find Full Text PDFPhenotypic screening reveals a highly selective phthalimide-based compound with antileishmanial activity.
PLoS Negl Trop Dis
March 2024
Drug Discovery and Evaluation Unit, Department of Parasitology, Faculty of Science, Charles University in Prague, Biocev, Vestec, Czech Republic.
Pharmacophores such as hydroxyethylamine (HEA) and phthalimide (PHT) have been identified as potential synthons for the development of compounds against various parasitic infections. In order to further advance our progress, we conducted an experiment utilising a collection of PHT and HEA derivatives through phenotypic screening against a diverse set of protist parasites. This approach led to the identification of a number of compounds that exhibited significant effects on the survival of Entamoeba histolytica, Trypanosoma brucei, and multiple life-cycle stages of Leishmania spp.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!