Malaria is a disease that has drawn worldwide attention due to the alarming rise of mortality rates particularly in third world countries. During the Plasmodium parasite intraerythrocytic life cycle, metabolic process...Malaria is a disease that has drawn worldwide attention due to the alarming rise of mortality rates particularly in third world countries. During the Plasmodium parasite intraerythrocytic life cycle, metabolic processes include the formation of hemozoin or malaria pigment. This pigment functions in the prevention of oxygen radical-mediated damage to the parasite. Drugs targeting hemozoin formation such as chloroquine and amodaquine are effective and are still used, but recently Plasmodium parasites have become resistant to these drugs, especially against chloroquine. In this study we looked at the potential use of two heterocyclic pyrimidine derivatives as anti-malaria drugs; 2,4-Diamino-6-Mercaptopyrimidine （DAMP） and 2-Mercaptopyrimidine （2-MP）. These compounds bear various coordination sites that enable them to react with metal ions to form coordination compounds. We used two methods for testing the inhibition of ferriprotoporphyrin IX （FP） biomineralisation： semi-quantitative microassay used by Deharo, and a quantitative assay used by G. Blaner and M. Akkawi. We report here the finding that （DAMP） has an in vitro inhibitory effect on I%hematin formation at concentrations and magnitude of nearly similar order to that of chloroquine, 2-MP was found to be effective but to a lower degree than DAMP.展开更多
Platinum-based anticancer drugs, including cisplatin and its analogues, have played important roles in the clinical treatment of solid tumors over the past 38 years. However, poor selectivity, high toxicity and intrin...Platinum-based anticancer drugs, including cisplatin and its analogues, have played important roles in the clinical treatment of solid tumors over the past 38 years. However, poor selectivity, high toxicity and intrinsic or acquired drug resistance profoundly limit their application, which encourages the development of novel transition metal-based anticancer agents with different mechanisms of action. To this end, transition metal complexes that can simultaneously act on more than one target, termed as single-molecule multi-targeting complexes, have attracted increasing attention because of their enhanced efficacy and diminished chance of drug resistance. In this review, we systematically discuss the recent progress in the development of platinum- and ruthenium-based anticancer agents, in particular the rational design of platinum and ruthenium complexes with multi-targeting features.展开更多
G-quadruplexes comprise a class of secondary structures that are formed in guanine-rich sequences in eukaryotic genomes and play a crucial role in the regulation of many biological events.G-quadruplexes have become ta...G-quadruplexes comprise a class of secondary structures that are formed in guanine-rich sequences in eukaryotic genomes and play a crucial role in the regulation of many biological events.G-quadruplexes have become targets for anticancer drugs with high selectivity vs.duplex DNA and low cytotoxicity against normal cells.Natural products and their derivatives display polymorphism,structural complexity,and potent activity.It is,therefore,reasonable to seek ligands targeting G-quadruplexes from natural products.Recently,many successful examples have been reported,showing ligands with excellent anticancer activities.In this review,we summarized the development of research on natural products and derivatives that target G-quadruplex structures in an effort to guide future studies.展开更多
文摘Malaria is a disease that has drawn worldwide attention due to the alarming rise of mortality rates particularly in third world countries. During the Plasmodium parasite intraerythrocytic life cycle, metabolic processes include the formation of hemozoin or malaria pigment. This pigment functions in the prevention of oxygen radical-mediated damage to the parasite. Drugs targeting hemozoin formation such as chloroquine and amodaquine are effective and are still used, but recently Plasmodium parasites have become resistant to these drugs, especially against chloroquine. In this study we looked at the potential use of two heterocyclic pyrimidine derivatives as anti-malaria drugs; 2,4-Diamino-6-Mercaptopyrimidine （DAMP） and 2-Mercaptopyrimidine （2-MP）. These compounds bear various coordination sites that enable them to react with metal ions to form coordination compounds. We used two methods for testing the inhibition of ferriprotoporphyrin IX （FP） biomineralisation： semi-quantitative microassay used by Deharo, and a quantitative assay used by G. Blaner and M. Akkawi. We report here the finding that （DAMP） has an in vitro inhibitory effect on I%hematin formation at concentrations and magnitude of nearly similar order to that of chloroquine, 2-MP was found to be effective but to a lower degree than DAMP.
基金supported by the National Natural Science Foundation of China(21135006,21127901,21275148,21301181,21321003,21575145)the National Basic Research Program of China(2013CB531805)
文摘Platinum-based anticancer drugs, including cisplatin and its analogues, have played important roles in the clinical treatment of solid tumors over the past 38 years. However, poor selectivity, high toxicity and intrinsic or acquired drug resistance profoundly limit their application, which encourages the development of novel transition metal-based anticancer agents with different mechanisms of action. To this end, transition metal complexes that can simultaneously act on more than one target, termed as single-molecule multi-targeting complexes, have attracted increasing attention because of their enhanced efficacy and diminished chance of drug resistance. In this review, we systematically discuss the recent progress in the development of platinum- and ruthenium-based anticancer agents, in particular the rational design of platinum and ruthenium complexes with multi-targeting features.
基金supported by the National Natural Science Foundation of China(21172272,21272291)
文摘G-quadruplexes comprise a class of secondary structures that are formed in guanine-rich sequences in eukaryotic genomes and play a crucial role in the regulation of many biological events.G-quadruplexes have become targets for anticancer drugs with high selectivity vs.duplex DNA and low cytotoxicity against normal cells.Natural products and their derivatives display polymorphism,structural complexity,and potent activity.It is,therefore,reasonable to seek ligands targeting G-quadruplexes from natural products.Recently,many successful examples have been reported,showing ligands with excellent anticancer activities.In this review,we summarized the development of research on natural products and derivatives that target G-quadruplex structures in an effort to guide future studies.
