| The outcome of tethering metal complexes with organic molecules can be dose reduction as well as resistance minimization.The conjugation of organic molecules with anticancer potential and metal complexes has been demonstrated to be a promising strategy for developing anticancer agents with multiple action mechanisms.Artesunate(ART),a chemical derivative of artemisinin,exerts diverse antitumor effects.However,ART possesses high side effect.Further,rhenium(Ⅰ)organometallic complexes are able to target mitochondria and Ruthenium(Ⅱ)complexes which can mimick iron show low toxicity.On the base of the anticancer viability of ART,we condensed rhenium(Ⅰ)organometallic complexes and Ruthenium(Ⅱ)complexes with ART.And further investigated for their anticancer activities.The antitumor mechanism has been explored.This paper consists of three chapters:In chapter 1,a series of Re(Ⅰ)/Ru(Ⅱ)complexes as well as artesunate researches about their anticancer activity have been described.In addition,PCD is also explained.In chapter 2,two ART conjugated phosphorescent rhenium(Ⅰ)complexes are designed and synthesized.Re(Ⅰ)–ART conjugates localize in mitochondria and induce mitochondrial dysfunction,thereby causing human cervical carcinoma(HeLa)cells death through a dual mode of apoptosis and ferroptosis.In chapter 3,six ART conjugated ruthenium(Ⅱ)complexes are designed and synthesized.Ru(Ⅱ)-ART conjugates can be effectively taken up by HeLa cells and selectively kill cancer cell lines.Mechanism studies have shown that Ru(Ⅱ)-ART conjugates can induce autophagy-dependent cell apoptosis. |
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