Neglected parasitic diseases (NTDs) are still considered one of the most prevalent public health problems in 149 tropical and subtropical countries affecting more than 1 billion people annually. The available chemical entities to treat neglected diseases such as malaria and schistosomiasis are associated with various limitations, in particular, the widespread drug resistance, severe adverse effects and the absence of financial attractive. Currently, the pharmaceutical treatment is still based on few chemical scaffolds. Thus, the development of new drugs active against Plasmodium falciparum and Schistosoma mansoni, obtained through an efficient and inexpensive synthesis, represents today a compelling priority. It is well known that some similar redox processes characterize the digestion of hemoglobin of the protozoon Plasmodium and the blood fluke Schistosoma and, on this basis, two effective antimalarials, artemisinin and mefloquine, have shown antischistosomal properties. Similarly, several natural and synthetic quinone derivatives have previously highlighted to be effective against both human parasistics. In this perspective, a number of compounds with dioxothiazine ring fused to the quinone moiety has been synthesized and a possible antimalarial and schistosomicidal activity has been investigated. Interestingly, the pharmacological results allowed to observe that the antiparasitic activity is most likely related to some structural requirements, in particular, the regiochemistry of dioxothiazine ring and the type of the substituents on the quinone play a crucial role on the antiparasitic effects. Overall these data clearly point out the thiazinoquinone scaffold as potential new lead structure for neglected disease drugs discovery.

The thiazinoquinone scaffold as chemical starting point for the design and synthesis of antiparasitic drugs

Marcello Casertano;Concetta Imperatore;Marialuisa Menna;Anna Aiello;Caterina Fattorusso;Paolo Luciano;Marco Persico;
2018

Abstract

Neglected parasitic diseases (NTDs) are still considered one of the most prevalent public health problems in 149 tropical and subtropical countries affecting more than 1 billion people annually. The available chemical entities to treat neglected diseases such as malaria and schistosomiasis are associated with various limitations, in particular, the widespread drug resistance, severe adverse effects and the absence of financial attractive. Currently, the pharmaceutical treatment is still based on few chemical scaffolds. Thus, the development of new drugs active against Plasmodium falciparum and Schistosoma mansoni, obtained through an efficient and inexpensive synthesis, represents today a compelling priority. It is well known that some similar redox processes characterize the digestion of hemoglobin of the protozoon Plasmodium and the blood fluke Schistosoma and, on this basis, two effective antimalarials, artemisinin and mefloquine, have shown antischistosomal properties. Similarly, several natural and synthetic quinone derivatives have previously highlighted to be effective against both human parasistics. In this perspective, a number of compounds with dioxothiazine ring fused to the quinone moiety has been synthesized and a possible antimalarial and schistosomicidal activity has been investigated. Interestingly, the pharmacological results allowed to observe that the antiparasitic activity is most likely related to some structural requirements, in particular, the regiochemistry of dioxothiazine ring and the type of the substituents on the quinone play a crucial role on the antiparasitic effects. Overall these data clearly point out the thiazinoquinone scaffold as potential new lead structure for neglected disease drugs discovery.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/737596
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