Title:Discovery and Investigation of 1-[4-(2-Aminoethoxy)Phenylcarbonyl]- 3,5-Bis-(Benzylidene)-4-Piperidones as Candidate Antineoplastic Agents: Our Last 15 Years Study
Volume: 28
Issue: 13
Author(s): Mohammad Hossain*, Carlos E. Enci, Jonathan R. Dimmock*Umashankar Das*
Affiliation:
- School of Sciences, Indiana University Kokomo, Kokomo, Indiana 46904,United States
- Drug Discovery and Development Research Cluster, University of Saskatchewan, Saskatoon S7N 5E5, Saskatchewan,Canada
- Drug Discovery and Development Research Cluster, University of Saskatchewan, Saskatoon S7N 5E5, Saskatchewan,Canada
Keywords:
Piperidones, unsaturated ketones, curcumin, anticancer, cytotoxic, antimalarial, antimycobacterial,
multi-drug resistance.
Abstract: This review outlines the discovery and development of a novel series of 1-[4-2-
aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-piperidones (5-8) as potential drug candidates
over the last 15 years in our laboratory. Many of these compounds demonstrate excellent cytotoxic
properties and are often more potent than contemporary anticancer drugs. Two highly important features
of many of these molecules are first, the greater tumour-selective toxicity and second, the ability of these
molecules to act as modulators of multi-drug resistance. The modes of action of some of the potent
compounds are by apoptosis induction, generation of reactive oxygen species, activation of certain
caspases and affecting mitochondrial functions. These molecules also display promising antimalarial and
antimycobacterial properties. In a short term toxicity study, these molecules are well tolerated in mice.
Structure-activity relationships and a drug delivery system along with pharmacokinetic studies and
metabolic stability of these compounds, have been presented. The positive characteristics associated
with the series (5-8) warrant their further evaluations as candidate antineoplastic drug candidates.