ArticleAnti-cancer agents in medicinal chemistry2024
Evaluation of Novel Benzo-annelated 1,4-dihydropyridines as MDR Modulators in Cancer Cells.
Article in Anti-cancer agents in medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Breaking the Efflux Barrier: P-Glycoprotein and Emerging Strategies to Overcome Multidrug Resistance in Cancer.Cancers · 2026Review
- Designing 1,4-Dihydropyridines-Based Multitarget Therapeutics: Recent Advances and Future Directions.Current topics in medicinal chemistry · 2025Review
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Authors and funding
4 authors.
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Abstract
backgroundMultidrug resistance (MDR) is the main problem in anticancer therapy today. Causative transmembrane efflux pumps in cancer cells have been reconsidered as promising anticancer target structures to restore anticancer drug sensitivity by various strategies, including MDR modulators. MDR modulators interfere with the efflux pumps and improve the cellular efficiency of chemotherapeutics. So far, only a few candidates have gone through clinical trials with disappointing results because of low specificity and toxic properties.
aimThis study aimed to find novel MDR modulators to effectively combat multidrug resistance in cancer cells.
objectiveWe synthesized various novel benzo-annelated 1,4-dihydropyridines to evaluate them as MDR modulators towards ABCB1 in cancer cells.
methodsSynthesized compounds were purified by column chromatography. The MDR modulation of ABCB1 was determined in cellular efflux assays using the flow cytometry technique and cellular fluorescent measurements by the use of each fluorescent substrate.
resultsCompounds were yielded in a two-step reaction with structurally varied components. Further, substituent- dependent effects on the determined MDR inhibiting properties towards ABCB1 were discussed. Cellular studies prove that there is no toxicity and restoration of cancer cell sensitivity towards the used anticancer drug.
conclusionNovel MDR modulators could be identified with favorable methoxy and ester group functions. Their use in both ABCB1 non-expressing and overexpressing cells proves a selective toxicity-increasing effect of the applied anticancer agent in the ABCB1 overexpressing cells, whereas the toxicity effect of the anticancer drug was almost unchanged in the non-expressing cells. These results qualify our novel compounds as perspective anticancer drugs compared to MDR modulators with nonselective toxicity properties.
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Registered trials
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