Identification of Compounds With Potential Dual Inhibitory Activity Against Drug Efflux Pumps in Resistant Cancer Cells and Bacteria: Protocol for a Systematic Review
Notice bibliographique
Résumé
BACKGROUND: Drug efflux mediated by transporter proteins is one of the major mechanisms conferring multidrug resistance (MDR) to antimicrobial agents in bacteria and to chemotherapeutics in cancer cells. Therefore, the development or identification of efflux modulators represents a promising strategy to overcome the resistant phenotype. Various chemical compounds have been tested in experimental studies as reversal agents either in combination with antimicrobial or anticancer drugs and have shown sensitizing activity in resistant bacteria or cancer cell lines. Owing to the common resistance mechanisms exhibited by bacteria and cancer cells, the identification of chemical agents with dual reversal activity offers a strategy to simultaneously combat antibacterial and cancer multidrug resistance. OBJECTIVE: This study aims to conduct a systematic review to identify compounds that have shown activity in reversing antibacterial as well as cancer MDR mediated by drug efflux pumps and to summarize their structural and biological parameters responsible for the interactions with drug efflux pumps. METHODS: The protocol has been developed in accordance with PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols) guidelines. We searched PubMed and Scopus databases for abstracts of full-text peer-reviewed journal papers in English language published between January 2012 and September 2024. Only studies from in vitro experiments were considered if they used methods to detect changes in antibiotic sensitivity of resistant bacteria and chemosensitivity of resistant cancer cells upon treatment with efflux pump inhibitors. A total of 763 unique records were identified. Of them, 246 were selected for full-text review based on the eligibility criteria. Abstract screening was performed by 2 independent reviewers. As of March 1, 2025, the systematic review is at the stage of completed abstract screening. The next steps of the full-text review, study selection, data extraction, and risk of bias assessment will be performed by 2 independent reviewers as well. Main data elements will include a structural identifier of the tested inhibitor, bacterial strain, cancer cell line, methods proving reversal activity, half maximal inhibitory concentration, and other relevant quantitative estimates of reversal activity. Data synthesis will be performed as a narrative summary and the content will be curated in tabular and graphical form. RESULTS: We anticipate that results from this study will outline the potential of various compounds to act as dual chemosensitizers and reverse both antimicrobial and cancer MDR. CONCLUSIONS: Our review will highlight the overlap between efflux pumps' inhibition as a strategy to combat MDR in both bacterial and cancer cells and it will provide structured data for rational drug design of dual efflux pump inhibitors. TRIAL REGISTRATION: PROSPERO CRD42024548350; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024548350. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/66197.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,042 | 0,067 |
| Méta-épidémiologie (sens strict) | 0,006 | 0,004 |
| Méta-épidémiologie (sens large) | 0,019 | 0,018 |
| Bibliométrie | 0,017 | 0,017 |
| Études des sciences et des technologies | 0,003 | 0,004 |
| Communication savante | 0,005 | 0,007 |
| Science ouverte | 0,004 | 0,004 |
| Intégrité de la recherche | 0,005 | 0,004 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,061 | 0,007 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».