Synthesis, Biological Activity and Preliminary in Silico ADMET Screening of Polyamine Conjugates with Bicyclic Systems

双环体系多胺结合物的合成、生物活性及初步计算机ADMET筛选

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作者:Marta Szumilak, Malgorzata Galdyszynska, Kamila Dominska, Irena I Bak-Sypien, Anna Merecz-Sadowska, Andrzej Stanczak, Boleslaw T Karwowski, Agnieszka W Piastowska-Ciesielska

Abstract

Polyamine conjugates with bicyclic terminal groups including quinazoline, naphthalene, quinoline, coumarine and indole have been obtained and their cytotoxic activity against PC-3, DU-145 and MCF-7 cell lines was evaluated in vitro. Their antiproliferative potential differed markedly and depended on both their chemical structure and the type of cancer cell line. Noncovalent DNA-binding properties of the most active compounds have been examined using ds-DNA thermal melting studies and topo I activity assay. The promising biological activity, DNA intercalative binding mode and favorable drug-like properties of bis(naphthalene-2-carboxamides) make them a good lead for further development of potential anticancer drugs.

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