Synthesis and Biological Evaluation of New Bischromone Derivatives with Antiproliferative Activity

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-4H-chromene-3-carboxylic acid 2 (or its methyl ester 3) and 4-oxo-4H-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-4H-chromene-3-carboxylic acid into 2H-chromene-2,4(3H)-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.

Crystal structure of 3-amino-9-methoxy-1-phenyl-1H-benzo[f]chromene-2-carbonitrile, C21H16N2O2

“…Chromene and benzochromene derivatives have attracted considerable interest owing to their biological and pharmaceutical activities such as antibacterial [1][2][3], antifungal [4][5][6], vascular-disrupting [7], antioxidant [8,9], anticancer [10][11][12][13], estrogenic anticoagulant and antispasmolytic [14], antileishmanial [15], antiproliferative and apoptosis inducing [16][17][18][19].…”

Anticancer activity of some polyamine derivatives on human prostate and breast cancer cell lines

“…1) used in this study, were chosen from previously synthesized and in vitro evaluated polyamine derivatives. Their synthesis and analytical data were described earlier (Szumilak et al, 2010;Trathnigg et al 1985, Szulawska-Mroczek et al, 2013. Both substances were dissolved immediately before the experiment at concentrations ranging from 5 μM to 50 μM for 3a and 5 μM to 90 μM for 5a.…”

“…Our quest for potential anticancer agents is focused on symmetrical polyamine derivatives with bicyclic terminal moieties designed according to bisintercalators' structural requirements (Szulawska-Mroczek et al, 2013;Szumilak et al, 2010). Bisintercalators are able to interact reversibly with double stranded (dsDNA) by simultaneous insertion of two chromophores usually tethered by a polyamine linker.…”

“…Our previous studies involving synthesis and biological in vitro evaluation of polyamine derivatives with various bicyclic moieties, revealed that polyamine derivatives with quinoline 3a and chromane 5a scaffolds (Fig. 1) are the most promising entities exhibiting antiproliferative activity toward a highly aggressive melanoma cell line A375 (Szulawska-Mroczek et al, 2013;Szumilak et al, 2010). Although the chemical structure of 5a was formerly known as a chelating agent (Trathnigg et al, 1985), we have obtained it by another route and assessed its antiproliferative activity together with other chromone/ chromane derivatives designed as potential bisintercalators (Szulawska-Mroczek et al, 2013).…”

An Efficient, Green, Catalyst Free Synthesis and Crystallographic Study of Benzo-4h-Pyrans in Aqueous Medium

“…[15] In particular, 2-Amino-4H-chromene derivatives are of recent interest for their antitumor activities. [16] In addition, 4H-chromene derivatives observed some biological and pharmacological effects such as treatment of advanced solid tumors, [17] blood anticoagulant warfarin, [18] anticancer therapeutic, [19] inhibitor of Bcl-2 protein and apoptosis inducer. [20] Multi-component reactions (MCRs) have been successfully employed to generate highly diverse combinatorial libraries for high-throughput screening of biological and pharmacological activities.…”