Marii Takahashi

Bio: Marii Takahashi is an academic researcher. The author has contributed to research in topics: Millettia & Diarylheptanoid. The author has an hindex of 5, co-authored 7 publications receiving 220 citations.

A sesquiterpenoic compound and pharmaceutical formulations comprising the same

Abstract: The objective of the present invention is to provide a pharmaceutically useful compound which is effective against drug resistant protozoans, particularly to leishmania. The objective can be achieved by using a sesquiterpenoic compound shown in formula (I), or a derivative thereof.

Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis.

Abstract: Leishmaniasis is a parasitic disease that presents four main clinical syndromes: cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), visceral leishmaniasis/kala azar (VL), and post kala azar dermal leishmaniasis (PKDL). Causative Leishmania are protozoan parasites that are transmitted among mammalian hosts by phlebotomine sandflies. In mammalian hosts, parasite cells proliferate inside the host phagocytic cells as round amastigotes. Infection of sandflies with Leishmania occurs during insect feeding on infected mammalian hosts. After introduction into the insect gut together with the blood meal, Leishmania amastigotes transform into elongated flagellated promastigotes that propagate in the insect gut. A new round of infection is initiated after the infected sandfly takes a blood meal from a naive mammalian host and introduces Leishmania parasites into the bite wound in the host dermis (Scheme 1). More than 20 different Leishmania species have been found to cause human leishmaniasis (Table 1). Leishmaniasis is endemic in 98 countries and is closely associated with poverty. More than a million new cases are reported per year and 350 million people are at risk of contracting the infection. For the most severe form of leishmaniasis, VL, ∼300 000 new cases are estimated to occur annually resulting in ∼40 000 deaths. Approximately 90% of all VL cases occur in 3 endemic foci: 1. India, Bangladesh, and Nepal; 2. East Africa; and 3. Brazil. In spite of the high prevalence, currently available treatments for leishmaniasis are inadequate. Pentavalent antimonials, the standard treatment for leishmaniasis for many decades, are not efficacious in Bihar (∼60% of VL cases worldwide) any longer due to widespread resistance to the drug in this region. Several new VL treatments have emerged during the past 10–15 years, but each has serious shortcomings (summarized in Table 2). These include paromomycin (injectable, long treatment, region-dependent efficacy), miltefosine (cost, teratogenicity, long treatment), and liposomal amphotericin B (cost, hospitalization, region-dependent efficacy). An additional challenge is represented by patients with HIV/VL coinfections who are more difficult to cure (lower initial and final cure rates), have greater susceptibility to drug toxicity, and have higher rates of death and relapse. Due to the limitations of the existing treatments, better drugs are urgently needed. Ideally, new VL drugs would be efficacious across all endemic regions, would affect cure in ≤10 days, and would cost <$10 per course (for a complete target product profile for new VL drugs, which was formulated by DNDi, see Table 4).1 Here we describe the disease history and parasite biology followed by a summary of the currently available treatments and, finally, review reports of novel small molecules with antileishmanial activity.

The Potential of Secondary Metabolites from Plants as Drugs or Leads Against Protozoan Neglected Diseases – Part I

Abstract: Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined by the WHO. Furthermore, malaria (caused by various Plasmodium species) can be considered a neglected disease in certain countries and with regard to availability and affordability of the antimalarials. Living organisms, especially plants, provide an innumerable number of molecules with potential for the treatment of many serious diseases. The current review attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs. In part I, a general description of the diseases, the current state of therapy and need for new therapeuticals, assay methods and strategies applied in the search for new plant derived natural products against these diseases and an overview on natural products of terpenoid origin with antiprotozoal potential were given. The present part II compiles the current knowledge on natural products with antiprotozoal activity that are derived from the shikimate pathway (lignans, coumarins, caffeic acid derivatives), quinones of various structural classes, compounds formed via the polyketide pathways (flavonoids and related compounds, chromenes and related benzopyrans and benzofurans, xanthones, acetogenins from Annonaceae and polyacetylenes) as well as the diverse classes of alkaloids. In total, both parts compile the literature on almost 900 different plant-derived natural products and their activity data, taken from over 800 references. These data, as the result of enormous efforts of numerous research groups world-wide, illustrate that plant secondary metabolites represent an immensely rich source of chemical diversity with an extremely high potential to yield a wealth of lead structures towards new therapies for NTDs. Only a small percentage, however, of the roughly 200,000 plant species on earth have been studied chemically and only a small percentage of these plants or their constituents has been investigated for antiprotozoal activity. The repository of plant-derived natural products hence deserves to be investigated even more intensely than it has been up to present.