ArticlePloS one2015
Inhibitors of the Candida albicans Major Facilitator Superfamily Transporter Mdr1p Responsible for Fluconazole Resistance.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 58 citations in OpenAlex.
- Lathyrane Diterpenoids: Half-Century of Chemical Insights and Therapeutic Potential.Plants (Basel, Switzerland) · 2026Review
- Advances in vulvovaginal candidiasis research: a comprehensive review from epidemiology, diagnosis, treatment to resistance mechanisms.Frontiers in microbiology · 2026Review
- Multidrug efflux pumps and innate azole resistance of Mucor lusitanicus.The Journal of antimicrobial chemotherapy · 2025Article
- Exploring Long Arm Amide-Linked Side Chains in the Design of Antifungal Azole Inhibitors of Sterol 14α-Demethylase (CYP51).Journal of medicinal chemistry · 2025Article
- Exploring the Arsenal of Novel Antifungal Drug Targets for Combating Fungal Infections.Current pharmaceutical biotechnology · 2025Review
- Azole Combinations and Multi-Targeting Drugs That Synergistically InhibitJournal of fungi (Basel, Switzerland) · 2024Review
- Overcoming Drug Resistance in a ClinicalAntibiotics (Basel, Switzerland) · 2023Article
- Clorgyline Analogs Synergize with Azoles against Drug Efflux inJournal of fungi (Basel, Switzerland) · 2023Article
- Atazanavir Resensitizes Candida auris to Azoles.Antimicrobial agents and chemotherapy · 2023Article
- Widespread genetic heterogeneity and genotypic grouping associated with fungicide resistance among barley spot form net blotch isolates in Australia.G3 (Bethesda, Md.) · 2023Article
- Functional Expression of RecombinantJournal of fungi (Basel, Switzerland) · 2023Article
- Characterisation ofJournal of fungi (Basel, Switzerland) · 2022Article
- The Application of Small Molecules to the Control of Typical Species Associated With Oral Infectious Diseases.Frontiers in cellular and infection microbiology · 2022Review
- Fungal Infections as an Uprising Threat to Human Health: Chemosensitization of Fungal Pathogens With AFP FromFrontiers in cellular and infection microbiology · 2022Review
- Curcumin affects function of Hsp90 and drug efflux pump ofFrontiers in cellular and infection microbiology · 2022Article
- Structural Insights into the Azole Resistance of theJournal of fungi (Basel, Switzerland) · 2021Article
- Low Glucose Mediated Fluconazole Tolerance inJournal of fungi (Basel, Switzerland) · 2021Article
- Directed Mutational Strategies Reveal Drug Binding and Transport by the MDR Transporters ofJournal of fungi (Basel, Switzerland) · 2021Review
- Mechanistic Understanding ofFrontiers in microbiology · 2021Review
- Potent Synergistic Interactions between Lopinavir and Azole Antifungal Drugs against Emerging Multidrug-Resistant Candida auris.Antimicrobial agents and chemotherapy · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTo identify a novel class of inhibitors of fungal transporters involved in drug resistance.
methodsA series of structurally-related low molecular mass compounds was synthesized using combinatorial chemistry of a cyclobutene-dione (squarile) core. These compounds were screened for their inhibition of plasma membrane Major Facilitator Superfamily (MFS) and ATP-binding cassette (ABC) transporters responsible for efflux pump-mediated drug resistance in the fungal pathogen Candida albicans. Strains of Saccharomyces cerevisiae that specifically overexpress the MFS pump CaMdr1p or the ABC transporter CaCdr1p were used in primary screens and counterscreens, respectively, and to detect inhibition of glucose-dependent Nile Red efflux. Efflux pump inhibition, activity as pump substrates and antifungal activity against yeast and clinical isolates expressing efflux pumps were determined using agarose diffusion susceptibility assays and checkerboard liquid chemosensitization assays with fluconazole.
resultsThe screen identified five structurally-related compounds which inhibited CaMdr1p. Two compounds, A and B, specifically chemosensitized AD/CaMDR1 to FLC in a pH-dependent fashion and acted synergistically with FLC in checkerboard liquid MIC assays but compound B had limited solubility. Compound A chemosensitized to FLC the azole-resistant C. albicans strain FR2, which over-expresses CaMdr1p, inhibited Nile Red efflux mediated by CaMdr1p but not CaCdr1p and was not toxic to cultured human cells. A minor growth-inhibitory effect of B on AD/CaMDR1, but not on AD/CaCDR1 and AD/CaCDR2, indicated that compound B may be a substrate of these transporters. The related compound F was found to have antifungal activity against the three pump over-expressing strains used in the study.
conclusionsCompound A is a 'first in class' small molecule inhibitor of MFS efflux pump CaMdr1p.
Indexed as
Identifiers
What OpenQuestion holds
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.