Semisynthetic phytochemicals in cancer treatment: a medicinal chemistry perspective

Cancer is the uncontrolled proliferation of abnormal cells that invade other areas, spread to other organs, and cause metastases, which is the most common cause of death. A review of all FDA-approved new molecular entities (NMEs) shows that natural products and derivatives account for over one-third of all NMEs. Before 1940, unmodified products and derivatives accounted for 43% and 14% of NME registrations, respectively. Since then, the share of unmodified products has decreased to 9.5% of all approved NMEs, while the share of derivatives has increased to 28%. Since the 1940s, semi-synthetic and synthetic derivatives of natural substances have gained importance, and this trend continues to date. In this study, we have discussed in detail isolated phytoconstituents with chemical modifications that are either FDA-approved or under clinical trials, such as podophyllotoxin, Taxol (paclitaxel, docetaxel), vinca alkaloids (vincristine, vinblastine), camptothecin, genistein, cephalotaxine, rohitukine, and many more, which may act as essential leads to the development of novel anticancer agents. Furthermore, we have also discussed recent developments in the most potent semisynthetic phytoconstituents, their unique properties, and their importance in cancer treatment.