Synthesis and In Vitro Screening of Novel Heterocyclic Compounds as Potential Breast Cancer Agents

Breast cancer is one of the most common non-cutaneous type of cancer in women in worldwide and a leading cause of cancer-related deaths, and is increasing year by year in almost every areas of the globe. Breast cancer is commonly classified into the following two major types: (1) non-invasive breast cancer (cancer cells are confined within the duct and lobules) and (2) invasive breast cancer (cancer cells invade through the walls of the duct or lobules and infiltrate the surrounding tissues). Various kinds of treatments are available for breast cancer, such as chemotherapy, radiotherapy and hormone therapy (Ragaz, 2009). Many indole derivatives are reported as potent breast cancer agents, such as aplysinopsin analogs and indole-3-carbinols. Aplysinopsins are indole-derived marine natural products. The parent aplysinopsin was isolated for the first time (Kazlauskas, et al, 1977) as the major metabolite of eight Indo-Pacific sponge species, which are representatives of the genus Thorecta. The N-1-unsubstituted aplysinopsins have generated considerable interest due to their potentially useful medicinal properties (Dobroslawa, et al, 2009). Aplysinopsin has been reported as a potent cytotoxic agent against the Kβ-cell line and methyl-aplysinopsins against L-1210 and Kβ-cell lines has been reported as potent cytotoxic agents (Hollenbeak & Schmitz, 1977), and the anticancer activities of aplysinopsin and methyl-aplysinopsins against both 1210and Kβ-cells has also been reported (Kondo et al. 1994). Indole-3-carbinol, a phytochemical derived from cruciferous vegetables such as broccoli and Brussel sprouts, exhibits potent antiproliferative effects against human breast cancer cells and has been shown to decrease metastatic spread of tumors in experimental animals (Brew, et al., 2010). From the above observations and as part of a program for the development of small molecules as potential anticancer treatments (Thirupathi Reddy, et al., 2010 and Narsimha Reddy et al., 2010), we initiated a drug discovery program to identify novel benzylaplysinopsin analogs as potent breast cancer agents. Combretastins are plant products from the South African tree Combretum caffrum. This compound was found to inhibit tubulin polymerization, and competitively inhibit the