Isamu Kanzaki

Objectives: Multiple myeloma and acute myeloid leukemia are severe forms of blood cancer, which lack effective therapies for treatment. In our search for new chemical lead structures from nature, we were investigating the Brazilian medicinal plant arnica-do-cerrado (Lychnophora ericoides). Methods: Repeated chromatography led to the isolation of four flavonoids and three sesquiterpenoids, which were evaluated for their cytostatic and cytotoxic properties against HL-60, MOLM-13, AMO-1, and KMS-12 PE cancer cells as well as the non-malignant HS-5 cell line. Results: Whereas the isolated flavonoids displayed only moderate activity, the three sesquiterpene lactones goyazensolide, centratherin, and lychnopholide exhibited pronounced effects against all four tested cell lines. Goyazensolide was the most effective compound, inhibiting proliferation and metabolic activity with IC₅₀ values between 1.0 and 1.6 µM, as well as 1.0 to 2.0 µM, respectively. Centratherin and lychnopholide were somewhat less active but showed higher selectivity towards malignant cell lines, which was most pronounced for MOLM-13 cells. Conclusion: The results of this study revealed interesting natural products that will be further evaluated for their potential as new lead compounds for the treatment of acute myeloid leukemia and multiple myeloma.

Emerging viruses pose enormous challenge to humanity. The sole member of the Nimaviridae family, in the genus whispovirus, the white spot syndrome virus, has spread to all around the world, and its infection cycle devastated shrimp aquaculture, menacing significatively the world market of food production. The comprehension of the mechanisms and factors involved in the emergence of novel viruses allow us to prevent and control the surge of new virus, and consequentially benefit the humanity, wherever avoiding human or animal disease acquisition, and particularly, to preserve food production from shrimp farming.

Novel antiretroviral drugs are constantly needed for human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients to confront the continuously emerging resistance to the commonly prescribed combination of anti-HIV synthetic agents and their side effects. Amazonian medicinal plants, Licania macrophylla (LM) (Chrysobalanaceae) and Ouratea hexasperma (OH) (Ochnaceae), were assayed for antiretroviral and immunomodulatory activity, by utilizing an established human leukocyte cell line and the simian immunodeficiency virus (SIV). Interleukin (IL)-4, IL-6, IL-8, IL-10, and interferon-gamma were quantified after leukocyte culture was stimulated with ethanolic plant extracts and subsequently challenged with lentivirus infection. Mitotic activity induced by OH extract was significantly more pronounced than that of LM extract. Cytokine modulation was observed in SIV-infected cells under independent treatment with OH and LM extracts. Betulinic acid, niruriflavone, (-)-epigallocatechin, (-)-gallocatechin, and 4’-O-methyl-epigallocatechin were isolated from LM. In summary, the tested extracts hold application potential in the therapy of HIV/AIDS pathology by regulating cellular proliferative activity and cytokine levels, as the isolated compounds from these plants have been reported to exhibit antiviral activity.

Background: Novel antiretroviral drugs are in constant need for HIV/AIDS patients to face the continuous emerging resistance to the commonly prescribed combination of anti-HIV synthetic agents and their side effects. Methods: Amazonian medicinal plants, Licania macrophylla (Chrysobalanaceae) and Ouratea hexasperma (Ochnaceae) were assayed for antiretroviral and immunomodulatory activity, utilizing an established human leukocyte cell line and the Simian Immunodeficiency Virus. The IL-4, IL-6, IL-8, IL-10 and IFN-y cytokines were quantified after leukocyte culture stimulation with ethanolic plant extracts and challenged with lentivirus infection. Results: Mitotic activity induced by O. hexasperma extract was significatively more pronounced than L. macrophylla extract. Cytokine modulation was recorded in SIV infected cells under independent treatment with O. hexasperma and L. macrophylla extracts. Betulinic acid, ninuriflavone, (-)epigallocathechine, (-)gallocatechine and 4-O-methyl-epigallocatechin were isolated from L. macrophyla . Conclusions: Cellular proliferative activity and cytokine modulation by the extracts assayed have potential applications in the therapy of HIV/AIDS pathology, as the isolated compounds of these plants have been reported for antiviral activity.

Vouacapoua americana (Fabaceae) is an economically important tree in the Amazon region and used for its highly resistant heartwood as well as for medicinal purposes. Despite its frequent use, phytochemical investigations have been limited and rather focused on ecological properties than on its pharmacological potential. In this study, we investigated the phytochemistry and bioactivity of V. americana stem bark extract and its constituents to identify eventual lead structures for further drug development. Applying hydrodistillation and subsequent GC-MS analysis, we investigated the composition of the essential oil and identified the 15 most abundant components. Moreover, the diterpenoids deacetylchagresnone (1), cassa-13(14),15-dien-oic acid (2), isoneocaesalpin H (3), (+)-vouacapenic acid (4), and (+)-methyl vouacapenate (5) were isolated from the stem bark, with compounds 2 and 4 showing pronounced effects on Methicillin-resistant Staphylococcus aureus and Enterococcus faecium, respectively. During the structure elucidation of deacetylchagresnone (1), which was isolated from a natural source for the first time, we detected inconsistencies regarding the configuration of the cyclopropane ring. Thus, the structure was revised for both deacetylchagresnone (1) and the previously isolated chagresnone. Following our works on Copaifera reticulata and Vatairea guianensis, the results of this study further contribute to the knowledge of Amazonian medicinal plants.

Genetic information exchange between virus and host cells apparently seems to be detrimental, as pluricellular organisms could develop diseases. Nevertheless, during billion years long evolutionary processes, the cell's genome revealed a mosaic of viral genomes or gene segments, giving rise to speculations that the genome of any cell was constructed and shaped by the invasion of virus genomes. But it could also be interpreted that the cellular genome is the source of autonomous gene segments that escaped from the cells, at some conditions, as a threat to the cell's survival. Quite commonly, oncogenic viruses integrate their genome in the host cell genome or interact in their episomal form. Some of these viruses cause lytic infection alternated with latent and persistent infection, leading to chronic inflammation, ultimately resulting in autoimmune diseases and cancer. Rarely, but potentially occurring, the genome of non-oncogenic RNA viruses could gain access to the cell nucleus, and eventually integrate their gene segments or genome in the host chromosome as it has been postulated for the current agent of the Corona Virus Disease 2019 (COVID-19), the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2). Rather than re-infection, SARS-CoV-2 gene activation, from host chromosome integrated material, would explain the detection of virus gene segments as in viremia. Therefore, viral capsids or solely viral gene segments, actively and selectively transported to the cell nucleus, could be found taking into account the exuberant virome reaching the cell nucleus to perform their replicative cycle. So, would the integration of unconventional reverse transcribed viral RNA of SARS-CoV-2, and of other RNA viruses, as the Bornaviruses, lead to the production of transcripts and proteins inducing antigenemia and stimulating constant immune response, or else would result in the excessive activation of neighboring cellular genes with pathogenic role to the host cell?