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ID: ALA1149759
Journal: Eur J Med Chem
Title: Cytotoxic 3,5-bis(benzylidene)piperidin-4-ones and N-acyl analogs displaying selective toxicity for malignant cells.
Authors: Pati HN, Das U, Quail JW, Kawase M, Sakagami H, Dimmock JR.
Abstract: A series of 3,5-bis(benzylidene)piperidin-4-ones 1, 1-acryloyl-3,5-bis(benzylidene)piperidin-4-ones 2 and adducts of 2 with sodium 2-mercaptoethanesulfonate (mesna), namely series 3, were prepared as candidate cytotoxic agents. These compounds were examined against neoplastic HSC-2, HSC-4 and HL-60 cells as well as HGF, HPC and HPLF normal cell lines and many of the compounds displayed selective toxicity for malignant cells. The CC50 values of the analogs in series 2 towards the cancer cell lines were mainly submicromolar. The relative potencies, selectivity and logP values were in the order of 2>1>3. The sulfonic acid group of a representative compound in series 3 was replaced by a thiol function to produce 4 leading to substantial increases in cytotoxic potencies and hydrophobicity indicating that the presence of a hydrophilic sulfonic acid group was disadvantageous in terms of potency. Molecular modeling suggested that the superior cytotoxicity of various members of series 1-3 over an acyclic analog 5 may have been due to the greater torsion angles theta1 and theta2 created between the arylidene aryl rings and the adjacent olefinic groups in series 1-3.
CiteXplore: 17499885