Praziquantel is the preferred treatment for schistosomiasis

Parasites can be parasitic on the body or surface of human through air, water, food and direct contact, and absorb nutrients from the host body to maintain the nutrition or shelter needed for survival, development and reproduction.

 

Parasites can be parasitic on the body or surface of human through air, water, food and direct contact, and absorb nutrients from the host body to maintain the nutrition or shelter needed for survival, development and reproduction. Although animals and plants can fend off parasites through immune function and the production of toxins, upsetting the balance between parasite populations and host immunity can lead to health problems. Parasitic diseases are of many kinds, widespread distribution and serious harm, especially in tropical and subtropical areas with poor and backward health conditions. Therefore, how to prevent and control parasitic diseases has become a public health issue of great concern. In addition to reducing exposure to parasites at source, selecting the right anti-parasite drugs for different parasite species is also critical.

 

 

Figure 1 Schistosomiasis causes severe fluid accumulation in the abdomen of African children (photo from the Internet)

 

The drug of choice for schistosomiasis

There are many kinds of parasitic diseases, among which schistosomiasis is the most widespread in the world. It is a tropical disease that seriously endangers human health and affects social and economic development. According to epidemiological surveys conducted by the World Health Organization, schistosomiasis is endemic in tropical and subtropical regions, especially in poor communities without access to safe drinking water and adequate sanitation facilities, and it is estimated that at least 90% of people in need of treatment for schistosomiasis live in Africa [1]. At present, chemical therapy is an important means to control schistosomiasis. Among these drugs, praziquantel is the first choice for treatment of schistosomiasis due to its advantages of high curative effect, short course of treatment and few adverse reactions. Praziquantel, developed by Bayer in the 1970s, not only has a good killing effect on various types of schistosomiasis, but also can be used for the prevention of high-risk groups, so it has a profound impact on the global control of schistosomiasis [2].

 

FIG. 2 Chemical structure of praziquantel and ball-and-stick model

 

Mechanism of action of praziquantel

Although praziquantel has been used in the treatment of schistosomiasis for more than 40 years, its mechanism of action has not been fully elucidated until now. In particular, the peculiar phenomenon that praziquantel has different effects on schistosomiasis at different developmental stages has not been thoroughly studied so far [3]. At present, the scientific community has put forward a variety of hypotheses for the mechanism of praziquantel. The mainstream view is that praziquantel may change the permeability of Ca2+ to the insect body, promote its internal flow, lead to the activity and muscle contracture of the insect body, and thus cannot be well adsorb to the vascular wall. On the other hand, it also affects the absorption, excretion, secretion and other functions of the insect body. The damage of the cortex of the insect body will also expose the antigen epitopes on the surface of the insect body, which will be recognized by the host immune system and eventually attract immune cells to gather around the insect body and attack it [4]. Therefore, the insecticidal mechanism of praziquantel can be summarized into two parts: the direct action of praziquantel on the insect body and the immune effect of the host.

 

FIG. 3 Different effects of praziquantel on Schistosoma japonicum at different developmental stages (picture from Reference 3)

 

Synthesis of praziquantel

It is not difficult to find that praziquantel molecule has a chiral center, theoretically there should be two chiral isomers, but fortunately the racemic of praziquantel does not cause harm to human body, although the left-handed isomer is more effective, racemic drugs are still used clinically. At present, a number of synthetic routes of praziquantel from different raw materials have been reported at home and abroad, and the initial route from isoquinoline of Bayer company is only introduced here. First, isoquinoline 1 is Reissert with benzoyl chloride and potassium cyanide to form dihydroisoquinoline derivatives. 2. Catalytic hydroreduction of unsaturated groups in molecules to generate new amide derivatives. 3. The compound can then be successfully prepared by acylation and intramolecular SN2 reaction. 4. Phosphoric acid heating condition water release debenzoyl. 5. Finally, praziquantel can be prepared by reacting with cyclohexyl benzoyl chloride. This method has mature technology, easy availability of raw materials and low cost.

 

Figure 4. Initial synthetic route of praziquantel

 

Applications and challenges of praziquantel

The advent of praziquantel opens a new chapter in the chemotherapeutics of schistosomiasis. Praziquantel is not only effective against all kinds of schistosomiasis infected human body, but also has the advantages of short course of treatment, high curative effect and few adverse reactions. However, the application of praziquantel still faces new challenges. In addition to the need to further elucidate the exact mechanism of insecticide, whether the long-term and heavy repeated use of praziquantel will lead to the development of drug resistance in insects has also aroused widespread concern. In view of this, it is particularly important to modify the structure of praziquantel and develop new praziquantel analogues. Currently, a variety of praziquantel derivatives have been reported, providing an important reference for subsequent drug development [6].

 

Figure 5. Representative novel praziquantel derivatives

 

Concluding remarks

The low toxicity and high efficiency praziquantel has opened up a new situation in the treatment of parasitic diseases especially schistosomiasis. However, the research on the mechanism of praziquantel and the resistance of schistosoma has not been a key breakthrough. It is noteworthy that the insecticidal mechanism of praziquantel may involve multiple targets, which in turn involve receptor proteins, enzymes, ion channels, transporters, nucleic acids and immune system of schistosoma japonicum, which obviously provides an important theoretical basis for the research and development of schistosoma drugs. Therefore, we can boldly expect that with the further study of the anti-parasitic mechanism of praziquantel, the development of novel anti-schistosomiasis drugs will have a broad prospect.

For more stainless hairline finish, sandblasted steel finish, hairline steelinformation, please contact us. We will provide professional answers.