ArticleJournal of medicinal chemistry2014
Propargyl-linked antifolates are dual inhibitors of Candida albicans and Candida glabrata.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 50 citations in OpenAlex.
- Chemoinformatics exploration of synthetically accessibleIn silico pharmacology · 2025Article
- Antimicrobial activities of metabolites isolated from endophytic Aspergillus flavus of Sarcophyton ehrenbergi supported by in-silico study and NMR spectroscopy.Fungal biology and biotechnology · 2023Article
- Promising Antifungal Molecules against Mucormycosis Agents Identified from Pandemic Response BoxJournal of fungi (Basel, Switzerland) · 2023Article
- Repurposing benzbromarone as antifolate to develop novel antifungal therapy for Candida albicans.Journal of molecular modeling · 2022Article
- Biological and computational studies provide insights intoBiochemistry and biophysics reports · 2021Article
- Dihydrofolate Reductase Is a Valid Target for Antifungal Development in the Human PathogenmSphere · 2020Article
- Characterization of trimethoprim resistantChemical science · 2017Article
- Direct Substitution of Arylalkynyl Carbinols Provides Access to Diverse Terminal Acetylene Building Blocks.Organic letters · 2017Article
- Crystal Structures of Trimethoprim-Resistant DfrA1 Rationalize Potent Inhibition by Propargyl-Linked Antifolates.ACS infectious diseases · 2016Article
- Propargyl-Linked Antifolates Are Potent Inhibitors of Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis.PloS one · 2016Article
- Synthesis, bioactivity, molecular docking and POM analyses of novel substituted thieno[2,3-b]thiophenes and related congeners.Molecules (Basel, Switzerland) · 2015Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Species of Candida, primarily C. albicans and with increasing prevalence, C. glabrata, are responsible for the majority of fungal bloodstream infections that cause morbidity, especially among immune compromised patients. While the development of new antifungal agents that target the essential enzyme, dihydrofolate reductase (DHFR), in both Candida species would be ideal, previous attempts have resulted in antifolates that exhibit inconsistencies between enzyme inhibition and antifungal properties. In this article, we describe the evaluation of pairs of propargyl-linked antifolates that possess similar physicochemical properties but different shapes. All of these compounds are effective at inhibiting the fungal enzymes and the growth of C. glabrata; however, the inhibition of the growth of C. albicans is shape-dependent with extended para-linked compounds proving more effective than compact, meta-linked compounds. Using crystal structures of DHFR from C. albicans and C. glabrata bound to lead compounds, 13 new para-linked compounds designed to inhibit both species were synthesized. Eight of these compounds potently inhibit the growth of both fungal species with three compounds displaying dual MIC values less than 1 μg/mL. Analysis of the active compounds shows that shape and distribution of polar functionality is critical in achieving dual antifungal activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.