Synthesis of artesunate hybrid derivatives containing chalcogen (O, S) and investigation of their anticancer properties in lung cancer cell lines

In order to improve existing drugs and develop new drugs, various methods have been proposed and new drug candidates have been synthesized. It is a fact that various natural products have been extensively used in drug research for the treatment of diseases. The main reason for this is the use of ointments and drugs derived from natural products and plants in the treatment of diseases since ancient times. Today, with the advancement of technology, organic synthesis studies and researches are helping to synthetically obtain and isolate natural products and use them in the treatment of new diseases. Looking at the literature, it is seen that there are quite a lot of natural products. Among these, the compound artemisinin, isolated from the wormwood plant (Artemisia annua), which was used in ancient Chinese medicine as an antipyretic and analgesic, has come to the fore in recent years. The natural product artemisinin was isolated and characterized by Dr. Tu Youyou and his team in the 1970s. The structure of artemisinin was found to be the most effective molecule in the treatment of malaria. In 2015, Dr. Tu Youyou was awarded the Nobel Prize in Medicine for the discovery of artemisinin. Today, the effects of artemisinin and its derivatives are also being studied in the treatment of various types of cancer. Artemisinin-containing molecules have been shown to have high biological activity. The synthesis of various artemisinin-containing heteroaromatic structures and their fields of application have been reviewed in the literature. In addition, a limited number of organometallic artemisinin-containing molecules have been synthesized. There is no synthesis of organometallic heteroaromatic structures with artemisinin compounds with proven biological activity and biological relevance. Ferrocene, an organometallic compound with high biological activity and used in cancer treatment, and its derivatives are also very important for medicinal chemistry research. In this study, new artemisinin-ferrocene hybrid structures with benzofuran/benzothiophene bridges were synthesized for the first time. According to the method developed by us, first ferrocenyl benzofuran/benzothiophene structures were regioselectively synthesized by electrophilic cyclization reaction and aldehyde derivatives were obtained by Suzuki-Miyaura reaction. In the last step, the artesunate structure was linked by an amide bridge. The structures of all compounds were elucidated by spectroscopic methods. In the last part of the study, their anticancer activity was tested against A549 lung cancer cells.