Design, Synthesis, and Preclinical Testing of Innovative Anti-Cancer Compounds with a High Level of Selectivity of Action and Low Toxicity

Despite several advances made towards the diagnosis, prevention, and treatment of cancer, it remains one of the major causes of human morbidity and mortality worldwide. This is a global challenge for social and health care systems, and it is therefore an urgent need to identify safe, long-term treatments for cancer.

Over the past decade multiple drugs have been developed against the proteins and biological pathways exploited by cancer cells through somatic mutations, however in most cases these drugs are only effective against a subset of cancers. These clinically used drugs also suffer from a variety of common problems, including side-effects on other tissues, low selectivity, and developed resistance during long-time treatment.

There is compelling evidence from epidemiological and experimental studies that highlight the importance of compounds derived from plant phytochemicals to reduce the risk of cancer and inhibit the development and spread of tumors in experimental animals. More than 25% of drugs used during the last 20 years are directly derived from plants, with many more being chemically altered natural products. The advantage of using such compounds for cancer treatment is their relatively non-toxic nature and availability in an ingestible form. An ideal phytochemical is one that possesses antitumor properties with minimal or no toxicity and has a defined mechanism of action.

This Research Topic aims to discuss the design of innovative small molecules as potential selective and safer anticancer agents, both synthetic and/or natural occurring. A major focus will be placed on the preclinical assessment of their anti-proliferative activity and selectivity, other than low toxicity. We will welcome manuscripts falling in these suggested topics:

• Hybridization of bioactive natural products and their activity, selectivity, and toxicity profiles
• Bioactive natural products inserted or anchored in inorganic matrices
• Feedback mechanisms leading to an acquired drug resistance
• Strategies to enhance the specificity to cancer cells and low toxicity to normal cells
• Success stories about combination therapies

We welcome submissions in the form of original research articles (a combination of chemistry with biological testing are preferred) and review articles.