title: 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.
authors.affiliation: Faculty of Medicine, Department of Molecular Biology of Cancer, Medical University of Lodz, 90-151 Lodz, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Szulawska-Mroczek
authors.forename: Marta
authors.initials: M
authors.lastname: Szumilak
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Szczesio
authors.forename: Andrzej
authors.initials: A
authors.lastname: Olczak
authors.forename: Ryszard B
authors.initials: RB
authors.lastname: Nazarski
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Lewgowd
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Czyz
authors.forename: Andrzej
authors.initials: A
authors.lastname: Stanczak
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D002867:Chromones