3,5-Bis(Phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones: A Novel Group of Cytotoxic Agents |
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| Authors: | JR DIMMOCK A JHA GA ZELLO RK SHARMA A SHRIVASTAV P SELVAKUMAR |
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| Institution: | 1. College of Pharmacy and Nutrition, University of Saskatchewan, S7N 5C9, Saskatoon, Saskatchewan, Canadadimmock@skyway.usask.ca;3. College of Pharmacy and Nutrition, University of Saskatchewan, S7N 5C9, Saskatoon, Saskatchewan, Canada;4. Department of Pathology, College of Medicine and Cancer Research Unit, Saskatoon Cancer Centre, S7N 4H4, Saskatoon, Saskatchewan, Canada |
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| Abstract: | A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones 3 have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity in these four screens. Molecular modeling revealed certain interplanar and bond angles and interatomic distances which were perceived to contribute to the observed bioactivity as well as providing suggestions for future structural modifications of the piperidones 3. Evaluation of representative compounds in series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at the maximum concentration utilized, namely 250?μM, only weak inhibiting properties were displayed by some of the compounds in series 4. Various members of series 3 and 4 were well tolerated in mice. |
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| Keywords: | 4-Piperidones Maleamic acids Cytotoxicity Molecular modeling Human N-myristoyltransferase |
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