Novel therapeutic candidate compound for Leishmaniasis isolated from Okinawan marine sponge

A research group led by Associate Professor Kanami Mori-Yasumoto of the Faculty of Pharmaceutical Sciences at Tokyo University of Science, Assistant Professor Takahiro Jomori of the Faculty of Science at the University of the Ryukyus, Associate Professor Yasuhiro Hayashi of the Faculty of Agriculture at the University of Miyazaki, Senior Researcher Mina Yasumoto-Hirose of Tropical Technology Plus, and Professor Emeritus Junichi Tanaka of the University of the Ryukyus isolated ten natural compounds from the Okinawan marine sponge Theonella sp. The isolated compounds include the novel compound onnamide G, which exhibits extremely high eradication activity against the parasitic protozoan Leishmania. Their findings were published online in Marine Biotechnology.

Leishmaniasis is a parasitic disease endemic to tropical and subtropical regions, with approximately 12 million people infected and an estimated 350 million at risk of infection. The disease is largely classified into cutaneous, mucosal, and visceral forms, with the most common being cutaneous leishmaniasis. As this type of leishmaniasis causes skin ulcers that result in lifelong scarring and can lead to severe physical disability and social stigma, an urgent need exists for the development and dissemination of treatment methods.

Current treatment methods include liposomal amphotericin B formulations, antimonial compounds, and miltefosine, but these face major challenges such as high toxicity, side effects, high costs, and drug resistance. Furthermore, due to insufficient vaccines and diagnostic methods, there is an urgent need for safer and more accessible therapies, particularly in endemic regions.

Among the compounds obtained, onnamide A and 6,7-dihydro-onnamide A demonstrated extremely high activity, approximately 53 and 315 times, respectively, that of amphotericin B, which is currently widely used. The above two onnamide compounds show low toxicity to human cells, with selectivity indices (indicators of efficacy and safety) exceeding 1000-fold. Furthermore, this study successfully elucidated the structure of onnamide G for the first time. This represents an important finding for unraveling the diversity of onnamides, and by comparing the structure of onnamide G with the structures and functions of existing onnamides, results were obtained that provide clues to elucidating the mechanism of action.

Onnamides isolated from the marine sponge subspecies Theonella sp. exhibit potent in vitro antileishmanial activity and possess high selectivity, suggesting their promise as lead compounds for the development of novel therapeutics. However, their complex molecular structures may pose challenges for chemical synthesis and large-scale production, necessitating further research.

A vision of "Saving lives through the power of chemistry"

Mori-Yasumoto commented: "We began this research with the desire to contribute to treatments that protect the lives and dignity of people around the world, even for diseases not seen in Japan. It pains me to think of the reality that patients living in regions without access to medicine suffer not only from the disease but also from social stigma. With the vision of 'saving lives through the power of chemistry,' I hope to address global medical challenges by leveraging the natural resources of Okinawa and Japan."

Journal Information
Publication: Marine Biotechnology
Title: Onnamides and a Novel Analogue, Onnamide G, as Potent Leishmanicidal Agents
DOI: 10.1007/s10126-025-10494-1