Recent Patents on Anti-Cancer Drug Discovery, Volume (13), No (2), Year (2018-2) , Pages (1-10)

Title : ( Synthesis and DFT study on Hantzsch reaction to produce asymmetrical compounds of 1,4-dihydropyridine derivatives for P-glycoprotein inhibition as anticancer agent )

Authors: Sh. Mollazadeh , Fatemeh Moosavi , F. Hadizadeh , M. Seifi , J. Behravan , M. Iman ,

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Abstract

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 of P-gp. 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 reactants. 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.

Keywords

, 1, 4-dihydropyridine; DFT study; Hantzsch reaction; P-glycoprotein; molecular orbital; synthesis
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@article{paperid:1069042,
author = {Sh. Mollazadeh and Moosavi, Fatemeh and F. Hadizadeh and M. Seifi and J. Behravan and M. Iman},
title = {Synthesis and DFT study on Hantzsch reaction to produce asymmetrical compounds of 1,4-dihydropyridine derivatives for P-glycoprotein inhibition as anticancer agent},
journal = {Recent Patents on Anti-Cancer Drug Discovery},
year = {2018},
volume = {13},
number = {2},
month = {February},
issn = {1574-8928},
pages = {1--10},
numpages = {9},
keywords = {1;4-dihydropyridine; DFT study; Hantzsch reaction; P-glycoprotein; molecular orbital; synthesis},
}

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%0 Journal Article
%T Synthesis and DFT study on Hantzsch reaction to produce asymmetrical compounds of 1,4-dihydropyridine derivatives for P-glycoprotein inhibition as anticancer agent
%A Sh. Mollazadeh
%A Moosavi, Fatemeh
%A F. Hadizadeh
%A M. Seifi
%A J. Behravan
%A M. Iman
%J Recent Patents on Anti-Cancer Drug Discovery
%@ 1574-8928
%D 2018

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