Source: European Journal of Medicinal Chemistry
Source: European Journal of Medicinal Chemistry

Goji berries (also known as wolfberries) are not only popular among the trendy health food crowd, but have also been used for centuries in East Asian food and medicine. Normally found dried, they can be consumed raw, in juice, tea, smoothies, added into trail mix, or as an ingredient in energy bars.

In a recent paper published in the European Journal of Medicinal Chemistry, two research groups led by Andrew Westwell, Ph.D., from Cardiff University and Karl Hoffmann, Ph.D., from Aberystwyth University, have turned the so called “superfruit” into a source of a potential treatment against the parasites that cause schistosomiasis and fasciolosis.

Their work is published in a paper entitled “Design, Synthesis and Anthelmintic Activity of 7-Keto-Sempervirol Analogues.”

Both schistosomiasis and fasciolosis are human parasitic worm infections that are considered Neglected Tropical Diseases. Schistosomiasis is currently treated with praziquantel, despite the compound’s poor effectiveness against the immature forms of the worms, resulting in reinfection. Fasciolosis is treated primarily with triclabendazole. However, large-scale use of single treatments tends to result in drug resistance, making the need for novel drug discovery an important research focus.

In this current work, the researchers built off of the previous understanding that a plant-derived compound isolated from Lycium chinense (one of the two plants that make goji berries), called 7-keto-sempervirol, displayed moderate levels of activity against both the juvenile and adult forms of the parasites that cause schistosomiasis and fasciolosis (Schistosoma mansoni and Fasciola hepatica, respectively.)

They sought to develop compounds based on 7-keto-sempervirol that would be more effective at killing these parasites. To do this, the 7-keto-sempervirol compound was subjected to medicinal chemistry optimization. Thirty similar, but novel, compounds were made and 25 were tested against the larval stage of S. mansoni.

The analog named “7d,” which performed best in the original screen, was also effective in the subsequent assays to test its anthelmintic properties against both worms. Importantly, 7d was found to affect both larval and adult schistosomes and inhibited egg production at the lowest test concentration. Its target was shown to be on the surface of the parasites, due to scanning electron microscopy data that revealed substantial tegumental alterations in both helminth species.

Although both parasitic infections are important public health concerns, the global burdens of the two are vastly different. At least 200 million people required preventive treatment for schistosomiasis in 2016 with some estimates of the total number of infected going as high as 600 million (with over 90% living in Africa), making it second only to malaria as the most devastating parasitic disease. Fasciolosis is an emerging disease with a fraction of the number of infections as schistosomiasis, but an estimated 180 million at risk of infection. That said, both infections are endemic in some areas, making a compound with dual anthelmintic activity an important discovery.

Regarding the research, Dr. Westwell commented, “Discovering a potential new treatment for two such prevalent diseases is an exciting find and we hope that this research will lead to major health benefits for some of the world's poorest people who are at risk of contracting schistosomiasis and fascioliasis.”

The researchers would like to create further modifications of 7d, with the hopes to create a new class of potent, broad-spectrum anthelmintic.

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