Formulation and Evaluation of Epoxides derived from oxygen heterocyclic compounds and Indane 1, 3 diones as possible specific targeting agents for cytotoxic activity

Abstract

The chemotherapy of neoplastic disease has become increasingly important in newlinerecent years. Most cancer patients now receive some form of chemotherapy even newlinethough it is merely palliative in many cases. The relatively high toxicity of most newlineanticancer drugs has fostered the development of supplementary drugs that may newlinealleviate these toxic effects or stimulate the regrowth of depleted normal cell. newlineThe term cancer and neoplastic disease actually encompass more than 100 newlinedifferent tumors each with its own unique characteristics. At present, at least 10 newlinedifferent neoplasms can be cured by chemotherapy in most patients. Cure is defined newlinehere is an expectation of normal longevity. These neoplasms are acute leukemia in newlinechildren, Burkitt s lymphoma, choriocarcinoma in women, Ewing s sarcoma, newlineHodgkin s disease, lymphosarcoma, mycosis fungoides, rhabdomyosarcoma, newlineretinoblastoma in children, and testicular carcinoma. Only these relatively rare newlineneoplasms are readily curable. newlineMTT assay of various test compounds against Ehrlich ascites carcinoma cell newlineline (Table No 1) proved that compound Cu-2 and IE-i, were significantly effective. newlineHence, these two compounds were selected for formulation into liposomal drug newlinedelivery system further. newlineIt was found that 7-(2and#8242;,3and#8242;-epoxypropoxy)-4-methylcoumarin (Cu-2) newlineexhibited favorable ED50 and hence they were subjected to cytotoxic evaluation by newlineMTT assay using methotrexate as a standard anticancer drug. newlineAll of them registered significant cytotoxic activity. However, Cu-2 was newlinefound to be significantly more active and toxicity study55,56,57,58 has been well newlineestablished. Therefore, Cu-2 was selected for formulation studies using liposomes as newlinedrug carriers. In order to compare the efficiency of the formulation of Cu-2, standard newlineanti-cancer drug methotrexate was also selected for formulation in a liposomal form. newline newline