Design, synthesis and characterization of artemisinin-pyrazole hybrid structures

In this study, the design, synthesis and characterization of new artemisinin-pyrazole hybrid derivatives were carried out by using artemisinin molecule isolated from wormwood plant as a natural product and pyrazoles with pentavalent ring system. The natural product Artemisinin molecule, discovered in 1970, is recognized as the most effective antimalarial drug in use today. In 2015, Chinese scientist Youyou Tu was awarded the Nobel Prize for his work on artemisinin. Then, it has been discovered that artemisinin derivatives are effective not only for the treatment of malaria but also for the treatment of different diseases such as cancer. The majority of studies have focused on the novel biological properties of artemisinin's semi-synthetic derivatives artesunate, artermer and dihydroartemisinin. In our study, new structures containing pyrazoles of known biological importance and artemisinin were designed and synthesized. Pyrazole and its derivatives are used as anti-cancer, anti-inflammatory, anti-depressant and anti-fungal. Pyrazoles based molecules have the potential to enhance existing biological activity. In the present study, firstly, the propargyl ketone derivatives were synthesized. Then, hydrazone intermediates were obtained from the reaction of propargyl ketone derivatives with hydrazines. The hydrazone derivatives were underwent to electrophilic cyclization reactions in the presence of iodine, 4-iodo pyrazole derivatives were obtained. SuzukiMiyaura coupling reaction was used for the formation of pyrazoles containing aldehydes required for the synthesis of the hybrid molecule. Accordingly, the desired aldehyde derivatives was synthesized when 4-iodopyrazoles and arylboronic acid derivatives reacted with palladium catalyst. In the last step, the aldehydes were converted to primary alcohol and primary amine structures which were then directly used to Sterligch reaction. Finally, new artemisinin-pyrazole derivatives containing ester and amide bridges were obtained with high yields. All intermediates and products were characterized by using spectroscopic methods.