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Synthesis and Biological Evaluation of New Bischromone Derivatives with Antiproliferative Activity
Author(s) -
SzulawskaMroczek Agata,
Szumilak Marta,
Szczesio Malgorzata,
Olczak Andrzej,
Nazarski Ryszard B.,
Lewgowd Wieslawa,
Czyz Malgorzata,
Stanczak Andrzej
Publication year - 2013
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201200220
Subject(s) - chemistry , piperazine , in vitro , stereochemistry , biological activity , reactivity (psychology) , cell cycle checkpoint , carboxylic acid , apoptosis , cell culture , chloride , chemical synthesis , molecule , structure–activity relationship , cell cycle , biochemistry , organic chemistry , biology , medicine , alternative medicine , pathology , genetics
Abstract The synthesis of new bischromone derivatives ( 4a – c and 5a – c ) as potential anticancer drugs is described. The difference in the reactivity between 4‐oxo‐4 H ‐chromene‐3‐carboxylic acid 2 (or its methyl ester 3 ) and 4‐oxo‐4 H ‐chromene‐3‐carbonyl chloride 1 with three different polyamines: 3,3′‐diamino‐ N ‐methyldipropylamine ( a ), 1,4‐ bis (3‐aminopropyl)piperazine ( b ), 4,9‐dioxa‐1,12‐dodecanediamine ( c ) resulted in the formation of two different groups of products, compounds 4a – c and 5a – c , designed in agreement with the bisintercalators' structural requirements. The transformation of 4‐oxo‐4 H ‐chromene‐3‐carboxylic acid into 2 H ‐chromene‐2,4(3 H )‐diones ( 5 ) was confirmed by the NMR and XRD experiments. Compounds 4a and 5a were evaluated in vitro in the highly aggressive melanoma cell line A375. An enhanced induction of apoptosis and cell cycle arrest clearly revealed that compound 5a was more potent than 4a . Compound 5a was also more active in diminishing the adhesive potential of melanoma cells. Current studies support the notion that small changes in the three‐dimensional structure of molecules might have a substantial impact on their biological activity.