Studies of some cytotoxic plant materials

Abstract

Cancer is a deadly disease all over the world. Modern treatments of cancer include surgical resection, radiation therapy, chemotherapy and phytomedicine. A strong effort has been put into the search for novel anticancer agents from medicinal plants since the early 1950s. A number of plant derived natural products are already in use in cancer therapy and many agents seem to be more promising for future use in cancer chemotherapy. Infectious diseases are the main causes of death accounting for approximately one-half of all deaths in tropical countries. Perhaps it is not surprising to see these statistics in developing nations, but what may be remarkable is that, mortality rates due to infectious diseases are actually increasing in developed countries, such as the United States. Death from infectious diseases, ranked 5th in 1981 and have become the 3rd leading cause of death in 1992, an increase of 58%. Bangladesh possesses a rich heritage of traditional medicines with a large number of medicinal plants available throughout the country. Therefore, it is essential to conduct research on these and other plants for isolating secondary metabolites which may have potential medical applications. Calycopteris floribunda Lam., commonly known as 'goichia lata or goache lata', is a large climbing woody shrub from Bangladesh, and is well distributed in a number of other south-east Asian countries. Traditionally, C. floribunda has been used as an anthelminthic, astringent and carminative, and for the treatment of diarrhoea, dysentery, jaundice and malaria in many countries including Bangladesh. Pachypodol (5,4'-dihydroxy-3,7,3'-trimethoxy flavone) (1) has been isolated from the leaves of C. floribunda by repeated column chromatography over silica gel, followed by crystallization. Its identity has been confirmed by spectroscopic means. While the general toxicity of pachypodol (1) was determined by the brine shrimp lethality assay, the cytotoxic potential of this flavonoid was evaluated by the Promega's Cell Titer 96® Non-Radioactive Cell Proliferation Assay using the CaCo 2 colon cancer cell line (IC50 = 185.6 µM). Two known compounds, stigmasterol (2) [Habib et al.2007] and oleanolic acid (3) [Hung et al. 2001] have also been isolated from the leaves of C. floribunda by repeated column chromatography over silica gel. Their identity has been confirmed by spectroscopic means as well. Solvent-solvent partitioning followed by column chromatography of the MeOH extract of the seeds of Swietenia mahagoni afforded two limonoids, a known compound swietenolide (4) [Kadota et al. 1990] and 2-hydroxy-3-0-tigloylswietenolide (5).The compounds were charaterized by spectroscopic means. This is the first report of isolation of compound 5 as a natural product. The antibacterial activity of these molecules was assessed against eight multiple-drug resistant bacterial strains (clinical isolates) by the conventional disc diffusion method. Although, both compounds were active against test organisms, compound 5 displayed overall more potent activity than compound 4. While the general toxicity of the two limonoids, swietenolide (4) and 2- hydroxy-3-0- tigloylswietenolide (5) were determined by the brine shrimp lethality assay, the cytotoxic properties of these limonoids were evaluated by the Promega's Cell Titer 96® Non-Radioactive Cell Proliferation Assay using the CaCo 2 colon cancer cell line. Although, swietenolide (4) and 2-hydroxyl-3-0-tigloyiswietenolide (5) showed no significant anticancer activity, surprisingly 2-hydroxyl-3-O-tigloylswietenolide (5) appeared to be cell growth promoter.