Design, synthesis and bioevaluation of novel maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones as cytostatic agents |
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| Authors: | Dani Youssef Elizabeth Potter Mamta Jha Erik De Clercq Jan Balzarini James P Stables Amitabh Jha |
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| Institution: | aDépartement des Sciences, Université Sainte-Anne, Pointe-de-l’Église, NÉ, Canada BOW 1MO;bDepartment of Chemistry, Acadia University, Wolfvile, NS, Canada B4P 2R6;cRega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium;dNational Institute of Neurological Disorders and Stroke, Rockville, MD 20852, USA |
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| Abstract: | A novel series of maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones were prepared to investigate the efficacy of micronutrient conjugation in enhancing cytotoxic potency by improving selectivity and delivery. These compounds, prepared as anticancer agents, were expected to demonstrate enhanced selectivity towards malignant cells through the inhibition of topoisomerase IIα via protein thiolation. The cytostatic effects of these compounds were evaluated against three cell lines, namely murine L1210 leukemia cells, human Molt 4/C8 and CEM T-lymphocyte cells. All compounds were found to have greater potency than the reference drug melphalan. Several compounds were found to potently inhibit topoisomerase IIα and displayed cytostatic activity in the nanomolar range. |
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| Keywords: | 3 5-Bisarylmethylene-4-piperidones Cytostatic activity Anticancer Topoisomerase inhibitions QSAR |
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