Background:
Multidrug 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.
Aim:
This study aimed to find Novel MDR modulators to effectively combat multidrug resistance in cancer cells.
Objective:
We synthesized various novel benzo-annelated 1,4-dihydropyridines to evaluate them as MDR modulators
towards ABCB1 in cancer cells.
Methods:
Synthesized 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.
Results:
Compounds 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 or restoration of cancer cell sensitivity towards the used anticancer drug.
Conclusion:
Novel 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.