Anticancer potential of Spiro-isoxazolidine derivatives of Parthenin

Abstract

The term cancer refers to a group of diseases which share similar characteristics. newlineCancer can affect all living cells in the body, at all ages and in both genders. The newlinecausation is multifactorial and the disease process differs at different sites. Apoptosis newlinecontributes to the anti-tumor activity of many chemotherapeutic drugs. The control newlineof cancer requires the effective implementation of knowledge derived from more newlinethan two decades of successful research. Drug discovery has been an essential newlinepursuit of mankind since prehistoric times. Because of the structural and biological newlinediversity of their constituents, terrestrial plants offer a unique, renewable resource for newlinethe discovery of potential new drug entities. The most pertinent question is how to newlinefind the needle (active compound) in the haystack. Traditional chemotherapy drugs newlineare indeed toxins. Most often, they kill all dividing cells; in addition to cancer cells, newlinethese often include hair follicles and the cells lining the intestine. Parthenium newlinehysterophorus L. (congress grass, carrot weed, wild feverfew) is an exotic weed that newlinewas accidentally introduced in India in 1956 through imported food grains. It has newlinebecome a common weed causing dermatitis of epidemic proportions. Parthenin, a newlinesesquiterpene lactone, is the major toxin present in Parthenium hysterophorous. The newlinespiro derivatives of parthenin are prepared and successfully tested as anticancer newlineagents and spiro-heterocyclic derivatives of parthenin exhibited improved newlinecytotoxicity as indicated by the in vitro cell based assay. newlineSeven spiro-isoxazolidine derivatives of parthenin were screened against HL-60 cells newlineand four compounds were selected on the basis of their lower IC50 values. These four newlinecompounds were subjected to MTT assay, Hoechst staining, Cell Cycle analysis and newlineDNA fragmentation to assess their in-vitro apoptotic potential.