Background: P-glycoprotein (P-gp) causes the efflux of cancer chemotherapy drugs from
tumor cells, so its inhibition can be one target for designing and synthesis of new anticancer drugs.
Objective: In this study, new compounds of 1,4-dihydropyridine (DHP) were recommended as inhibitors
Methods: We synthesized new symmetrical DHP with 36% - 43% yield by the reaction of new reactants.
In biological studies, these compounds have high lipophilicity, and thus low water solubility. Four
reactants I with different reactivity was computed and compared using DFT study. The LUMO-map was
differently distributed on each reactant. Amine intermediate underwent tautomerism as a transition state
and it seems to play important role in reaction progress. Calculations were performed to select suitable
Results: Two different reactants I, including one polar group and a non-polar group, were used to produce
asymmetric compounds with 49% - 60% yield. These asymmetric DHPs were more soluble than
symmetric DHPs. In the final step, another selected symmetric product (by the elimination of chlorine
atom) was synthesized in high yield (74%) by using DFT study.
Conclusion: In this study, selected reactants by DFT calculation have increased the yield of reaction
from 36% to 74% without any catalyst. The diversity of products is a noticeable topic. Racemic asymmetric
compounds with R and S enantiomers have the potential for enantiomeric separation. Each of
these enantiomers could have a different physiological effect.