Design and synthesis of podophyllotoxin, phenanthrene and pyrazole based hybrids as potential anticancer agents

The search for novel and effective drugs is a priority goal for treatment of cancer, due to the rapid development of resistance to chemotherapeutic drugs. Moreover, high toxicity usually associated with some cancer chemotherapy drugs and their undesirable side-effects increase the demand for novel anti-tumor drugs active against untreatable tumors, with fewer side-effects and/or greater therapeutic efficiency. Natural products play an important role in the development of anti-cancer drugs. 30 % of anti-tumor compounds used in medicine are natural products or close relatives of them. However, the number of natural products is limited; millions of hybrids can be prepared as combinations of or parts of different natural products. This new approach seems to be very promising in the development of lead compounds for medicinal use, as the biological activity of many new hybrids is superior to their parent compounds.

This concept offers an advantage of high diversity and the inherent biological properties of the hybrids over a combinatorial chemistry. By taking the advantage of hybrid concept, in this thesis different series of new podophyllotoxin, phenanthrene and pyrazole based hybrids were synthesized with a view to produce promising anticancer agents. All the synthesized hybrid molecules were investigated for their anticancer activity on different cancer cells. Some of the synthesized hybrid molecules displayed either improved cytotoxicity or higher binding affinity to the target in comparison to their individual parent compounds. Based on the results from the biological studies; it is evident that some of the synthesized compounds have the potential to be developed as leads and their further structural modifications may produce promising anticancer agents.