Editorial to the Feature article “Artemisinin anti-malarial drugs in China”

The winning of the 2015 Nobel Prize in Physiology or Medicine by William C. Champbell, Satoshi Omura, and the Chinese scientist Youyou Tu marks their pioneering discoveries of novel therapeutic drugs to treat highly devastating parasitic diseases that mostly affect the world’s poorest populations, such as river blindness, lymphatic filariasis, and malaria. More appreciably, this is also the first time that a Chinese scientist was awarded this Noble Prize. Professor Youyou Tu is a natural product medicinal chemist at the China Academy of Chinese Medical Sciences who made significant contribution to the discovery of artemisinin as an antimalarial drug. Back in the 1960s, malaria was the most common and widespread parasitic disease in tropical and subtropical regions, which killed millions of lives annually. Fortunately, China, under the “whole nation” system, launched a multidisciplinary drug discovery team that involved hundreds of scientists nationwide, including Youyou Tu. Their efforts led to the discovery of many antimalarial drugs or drug candidates, including artemisinin, dihydroartemisinin, artemether, and artesunate. Several of these drugs have been used since then as the standard treatment for P. falciparum and saved millions of malarial patients worldwide.

The discovery of artemisinin is a miracle in the history of Chinese pharmaceutical industry, especially during that special period of time when China was enduring a particularly difficult time with endemic poverty and the disastrous culture revolution. Many elegant reviews have been published recently (e.g., Nat. Prod. Rep. 2015; 32: 1617–21), walking through the historical discovery process of artemisinin, and with efforts to find insights or implications both to enlighten the currently much modernized drug discovery world and to encourage old and young generations of scientists working with the traditional Chinese medicines (TCMs).

This Feature written by Prof. Zongru Guo is a timely account highlighting the most important aspects of the artemisinin story, including the initial discovery of artemisinin as the active component, subsequent structural characterization, total synthesis, and structural modification, as well as the identification and clinical validation of the most important antimalarial drugs artemether, artesunate and dihydroartemisinin. From a medicinal chemist’s viewpoint, this review also provides expert discussions on the QSAR, structure-based physico–chemical properties, drug-likeness developments, and formulation studies of artemisinin analogs. As emphasized, the success of artemisinin was the fruit of collaborative teamwork by a large number of multidisciplinary scientists, including natural product chemists who identified the active compound from natural sources, organic chemists who elucidated the precise chemical structure, medicinal chemists who tuned the safety profiles through structural optimization, and pharmacologists and clinicians who made tremendous efforts to validate the effects of artemisinin and its analogs both in vitro and in vivo. In the meantime, we have to be aware that the success of artemisinin or the recognition by the Nobel Prize does not mean that the fight against the tropical disease is over; instead, we have to work much harder to find new and further improved treatments since drug resistance to artemisinin therapies has already been reported.