LE3 .A278 2004

2004

Jha, Amitabh

Acadia University

Bachelor of Science

Honours

Chemistry

Chemistry

Electrophilic compounds, like N-mustards (e.g. Alkeran®) have long been used as powerful anti-cancer agents because of their ability to alkylate nucleic acids. Owing to this non-selective genotoxic behaviour, DNA damage to other normal cells sometimes triggers mutagenesis and carcinogenesis. This investigation deals with discovery of nongenotoxic alkylating agents which are selectively cytotoxic to cancerous cells by inhibiting vital enzyme systems. Use of compounds containing α-β unsaturated ketone systems is gaining importance as electrophilic centers for alkylation of cellular proteins. α,β-Unsaturated ketones have a remarkable affinity for thiol groups (abundant on proteins) and little or no affinity for hydroxyl and amino groups (present on nucleic acids) under physiological conditions. Consequently, a series of 1-arylidene-3,4-dihydro-3- (phenylallylidene)-naphthalen-2(1H)-ones were designed and successfully synthesized as anti-neoplastic agents. These compounds were characterized by spectroscopic techniques. Biological evaluation in relevant assay systems indicated that these compounds possess moderate selective cytotoxicity towards human cancer lines and displayed excellent preliminary safety profiles. Structure-activity relationship studies indicated that the anticancer activity of these compounds can be enhanced by appropriate modification in the structure which will form bases of future investigations.

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https://scholar.acadiau.ca/islandora/object/theses:429