Massuo Jorge Kato - University of Sao Paulo (original) (raw)

Papers by Massuo Jorge Kato

Frontiers in Chemistry

Plasmodium falciparum is the etiological agent of human malaria, one of the most widespread disea... more Plasmodium falciparum is the etiological agent of human malaria, one of the most widespread diseases in tropical and subtropical regions. Drug resistance is one of the biggest problems in controlling the disease, which leads to the need to discover new antimalarial compounds. One of the most promissory drugs purposed is fosmidomycin, an inhibitor of the biosynthesis of isoprene units by the methylerythritol 4-phosphate (MEP) pathway, which in some cases failed in clinical studies. Once formed, isoprene units are condensed to form longer structures such as farnesyl and geranylgeranyl pyrophosphate, which are necessary for Heme O and A formation, ubiquinone, and dolichyl phosphate biosynthesis as well as for protein isoprenylation. Even though the natural substrates of polyprenyl transferases and synthases are polyprenyl pyrophosphates, it was already demonstrated that isoprenoid alcohols (polyprenols) such as farnesol (FOH) and geranylgeraniol (GGOH) can rescue parasites from fosmido...

Brazilian Journal of Biology

Several Piper species accumulate piperamides as secondary metabolites, and although they have rel... more Several Piper species accumulate piperamides as secondary metabolites, and although they have relevant biological importance, many details of their biosynthetic pathways have not yet been described experimentally. Experiments involving enzymatic reactions and labeled precursor feeding were performed using the species Piper tuberculatum and Piper arboreum. The activities of the phenylalanine ammonia lyase (PAL) enzymes, which are involved in the general phenylpropanoid pathway, were monitored by the conversion of the amino acid L-phenylalanine to cinnamic acid. The activity of the 4-hydroxylase (C4H) enzyme was also observed in P. tuberculatum by converting cinnamic acid to p-coumaric acid. L-[UL-14C]-phenylalanine was fed into the leaves of P. tuberculatum and incorporated into piperine (1), 4,5-dihydropiperine (2), fagaramide (4), trans-piplartine (7), and dihydropiplartine (9). In P. arboreum, it was only incorporated into the piperamide 4,5-dihydropiperiline (3). L-[UL-14C]-lysin...

Metabolites

Toxoplasmosis is a tropical and neglected disease caused by the parasitic protozoa Toxplasma gond... more Toxoplasmosis is a tropical and neglected disease caused by the parasitic protozoa Toxplasma gondii. Conventional treatment with sulfadiazine and pyrimethamine plus folinic acid, has some drawbacks, such as inefficacy in the chronic phase, toxic side effects, and potential cases of resistance have been observed. In this study, the activity of essential oils (EOs) from three Piper species and their main constituents, including α-Pinene (Piper lindbergii and P. cernuum), β-Pinene (P. cernuum), and dillapiole (P. aduncum), were evaluated against tachyzoites of T. gondii. α-Pinene was more active [(IC50 0.3265 (0.2958 to 0.3604) μg/mL)] against tachyzoites than P. lindbergii EO [0.8387 (0.6492 to 1.084) μg/mL]. Both α-Pinene and P. lindbergii EO exhibited low cytotoxicity against NHDF cells, with CC50 41.37 (37.64 to 45.09) µg/mL and 83.80 (75.42 to 91.34) µg/mL, respectively, suggesting they could be of potential use against toxoplasmosis.

Plants

Plastoquinone is a key electron carrier in photosynthesis and an essential cofactor for the biosy... more Plastoquinone is a key electron carrier in photosynthesis and an essential cofactor for the biosynthesis of carotenoids. p-Hydroxyphenylpyruvate dioxygenase (HPPD) is a vital enzymatic step in plastoquinone biosynthesis that is the target of triketone herbicides, such as those derived from the pharmacophore backbone of the natural product leptospermone. In this work, the inhibitory activity of a series of 2-acyl-cyclohexane-1,3-diones congeners derived from Peperomia natural products was tested on plant HPPD. The most active compound was a 2-acyl-cyclohexane-1,3-dione with a C11 alkyl side chain (5d; I50app: 0.18 ± 0.02 μM) that was slightly more potent than the commercial triketone herbicide sulcotrione (I50app: 0.25 ± 0.02 μM). QSAR analysis and docking studies were performed to further characterize the key structural features imparting activity. A 1,3-dione feature was required for inhibition of HPPD. Molecules with a side chain of 11 carbons were found to be optimal for inhibiti...

Molecules

Aniba rosiodora has been exploited since the end of the nineteenth century for its essential oil,... more Aniba rosiodora has been exploited since the end of the nineteenth century for its essential oil, a valuable ingredient in the perfumery industry. This species occurs mainly in Northern South America, and the morphological similarity among different Aniba species often leads to misidentification, which impacts the consistency of products obtained from these plants. Hence, we compared the profiles of volatile organic compounds (essential oils) and non-volatile organic compounds (methanolic extracts) of two populations of A. rosiodora from the RESEX and FLONA conservation units, which are separated by the Tapajós River in Western Pará State. The phytochemical profile indicated a substantial difference between the two populations: samples from RESEX present α-phellandrene (22.8%) and linalool (39.6%) in their essential oil composition, while samples from FLONA contain mainly linalool (83.7%). The comparison between phytochemical profiles and phylogenetic data indicates a clear differen...

Química Nova

ENT-ABIETANE DITERPENES FROM Euphorbia phosphorea (EUPHORBIACEAE). Phytochemical study of the roo... more ENT-ABIETANE DITERPENES FROM Euphorbia phosphorea (EUPHORBIACEAE). Phytochemical study of the roots of Euphorbia phosphorea Mart. (Euphorbiaceae) was carried out through chromatographic techniques, resulting in the isolation of a new ent-abietane diterpene named 11β,12β-dihydroxy-ent-abieta-8(14),13(15)-dien-16,12α-olide (1), and of nine known ent-abietane diterpenes jolkinolide A (2), jolkinolide E (3), euphorin H (4), euphopilolide (5) jolkinolide F (6), ent-12-hydroxy-12[R]-abieta8(14),13(15)-dien-16,12-olide (7), ent-11α-hydroxyabieta-8(14),13(15)-dien-16,12α-olide (8), 17-hydroxyjolkinolide B (9) and caudicifolin (10). The structures of all compounds were established using spectroscopic techniques such as 1D and 2D NMR, and the structure of the compound 1 was established also with MS, IR and ECD. All compounds were submitted to an in silico study through of a predictive model and then submitted to in vitro tests against Mycobacterium tuberculosis and M. smegmatis for evaluation...

Research, Society and Development

Objetivo: Avaliar a atividade desses compostos nas formas sexuadas do Plasmodium falciparum e det... more Objetivo: Avaliar a atividade desses compostos nas formas sexuadas do Plasmodium falciparum e determinar as propriedades farmacocinéticas teóricas dos compostos utilizando ensaios in silico. Métodos: Para a avaliação da inibição das formas exflagelantes foi utilizada a cepa de Plasmodium falciparum NF54 para a produção de gametócitos in vitro. Para os testes in silico foi utilizado o programa ADMETlab buscando identificar as propriedades farmacocinéticas teóricas de todos os compostos. Resultados: A série de amidas naturais e sintéticas testadas não se destacaram como possíveis bloqueadores de transmissão da malária. Porém, mostraram inibição moderada no bloqueio da exflagelação. Os resultados do screening virtual permitiram conhecer e explorar as propriedades farmacocinéticas teóricas interessantes dessa classe de compostos, como a permeabilidade moderada as células Caco-2 do composto 14f; as substâncias mostram-se nocivas mais não letais (DL50); somente o composto 14f pode causar ...

Frontiers in Cellular and Infection Microbiology

Malaria is one of the most widespread parasitic diseases, especially in Africa, Southeast Asia an... more Malaria is one of the most widespread parasitic diseases, especially in Africa, Southeast Asia and South America. One of the greatest problems for control of the disease is the emergence of drug resistance, which leads to a need for the development of new antimalarial compounds. The biosynthesis of isoprenoids has been investigated as part of a strategy to identify new targets to obtain new antimalarial drugs. Several isoprenoid quinones, including menaquinone-4 (MK-4/vitamin K2), α- and γ-tocopherol and ubiquinone (UQ) homologs UQ-8 and UQ-9, were previously detected in in vitro cultures of Plasmodium falciparum in asexual stages. Herein, we described for the first time the presence of phylloquinone (PK/vitamin K1) in P. falciparum and discuss the possible origins of this prenylquinone. While our results in metabolic labeling experiments suggest a biosynthesis of PK prenylation via phytyl pyrophosphate (phytyl-PP) with phytol being phosphorylated, on the other hand, exogenous PK at...

Journal of the Brazilian Chemical Society, 2017

Piper gaudichaudianum Kunth (Piperaceae) accumulates gaudichaudianic acid, a prenylated benzopyra... more Piper gaudichaudianum Kunth (Piperaceae) accumulates gaudichaudianic acid, a prenylated benzopyran, as its major component. Interestingly, this trypanocidal compound occurs as a racemic mixture. Herein, transcriptomic investigations of Piper gaudichaudianum using the RNAseq approach are reported, and from the analysis of the transcripts expressed it was possible to propose a complete biosynthetic pathway for the production of gaudichaudianic acid, including the steps that originate its precursor, p-hydroxybenzoic acid. Peperomia obtusifolia (L.) A. Dietr. (Piperaceae) also accumulates racemic benzopyrans, however, its chromanes originate from the polyketide pathway, while the chromenes from Piper derives from the shikimate pathway. Recent transcriptomic and proteomic studies of the former species did not identify polyketide synthases involved in the production of the benzopyran moiety, but revealed the expression of tocopherol cyclase, which may be responsible for the cyclization of the 3,4-dihydro-2H-pyran ring. The analysis of the enzymes involved in the secondary metabolism of Piper gaudichaudianum and the comparison with the data previously obtained from Peperomia obtusifolia can provide valuable information on how these compounds are biosynthesized.

Frontiers in Pharmacology, 2022

Urodele amphibians (∼768 spp.), salamanders and newts, are a rich source of molecules with bioact... more Urodele amphibians (∼768 spp.), salamanders and newts, are a rich source of molecules with bioactive properties, especially those isolated from their skin secretions. These include pharmacological attributes, such as antimicrobial, antioxidant, vasoactive, immune system modulation, and dermal wound healing activities. Considering the high demand for new compounds to guide the discovery of new drugs to treat conventional and novel diseases, this review summarizes the characteristics of molecules identified in the skin of urodele amphibians. We describe urodele-derived peptides and alkaloids, with emphasis on their biological activities, which can be considered new scaffolds for the pharmaceutical industry. Although much more attention has been given to anurans, bioactive molecules produced by urodeles have the potential to be used for biotechnological purposes and stand as viable alternatives for the development of therapeutic agents.

Frontiers in Plant Science, 2021

The continuous and indiscriminate use of insecticides has been responsible for the emergence of i... more The continuous and indiscriminate use of insecticides has been responsible for the emergence of insecticide resistant vector insect populations, especially in Aedes aegypti. Thus, it is urgent to find natural insecticide compounds with novel mode of action for vector control. The goal of this study was to investigate the larvicidal activity of essential oils (EOs) from Piper species against A. aegypti characterized as resistant and susceptible strains to pyrethroids. The EOs from leaves of 10 Piper species were submitted to the evaluation of larvicidal activity in populations of A. aegypti in agreement with the (World Health Organization, 2005) guidelines. The resistance of the strains characterized by determining the lethal concentrations (LCs) with the insecticide deltamethrin (positive control). The major compounds of the EOs from Piper species was identified by GC-MS. The EOs from Piper aduncum, P. marginatum, P. gaudichaudianum, P. crassinervium, and P. arboreum showed activity...

PeerJ, 2021

The genus Eois Hübner (Geometridae: Larentiinae) comprises 254 valid species, 217 of which were d... more The genus Eois Hübner (Geometridae: Larentiinae) comprises 254 valid species, 217 of which were described from the Neotropics and 31 of those having their type locality in Brazil. Since this species rich genus has never been revised, and may potentially include many cryptic undescribed species, Eois embodies a problematic taxonomic scenario. The actual diversity of Eois is greatly underestimated and the Brazilian fauna is poorly known, both because of inadequate sampling and because of the potential existence of cryptic species "hidden" within some nominal taxa. In this study we investigated the diversity within a cryptic species complexes associated to the E. pallidicosta and E. odatis clades. We describe three new species Eois oya Moraes & Montebello sp. nov., Eois ewa Moraes & Stanton sp. nov., and Eois oxum Moraes & Freitas sp. nov., in an integrative taxonomy approach, using morphology, host plant use and species delimitation tools.

The chemical profile of Piper nigrum cultivars showed different variations during infection by F.... more The chemical profile of Piper nigrum cultivars showed different variations during infection by F. solani f. sp. piperis.

Eclética Química Journal, 2018

The phytochemical study on dichlorometane extracts of leaves, stem and roots of Piper mollicomum ... more The phytochemical study on dichlorometane extracts of leaves, stem and roots of Piper mollicomum Kunth (Piperaceae) led to isolation of the known piperamides tembamide (1), (R)-(-)-tembamide acetate (2) and riparin I (3). Compounds 1 and 2 displayed moderate in vitro antifungal activity against Cladosporium cladosporioides (5.0 μg) and Cladosporium sphaerospermum (1.0 μg) by direct bioautographic analyses and compound 3 was inactive up to 100.0 μg.

SummaryOver evolutionary timescales, shifts in plant secondary chemistry may be associated with p... more SummaryOver evolutionary timescales, shifts in plant secondary chemistry may be associated with patterns of diversification in associated arthropods. Although foundational hypotheses of plant-insect codiversification and plant defense theory posit closely related plants should have similar chemical profiles, numerous studies have documented variation in the degree of phylogenetic signal, suggesting phytochemical evolution is more nuanced than initially assumed. We utilize proton nuclear magnetic resonance (1H NMR) data, chemical classification, and genotyping-by-sequencing to resolve evolutionary relationships and characterize the evolution of secondary chemistry in the Neotropical plant clade Radula (Piper; Piperaceae). Sequencing data substantially improved phylogenetic resolution relative to past studies, and spectroscopic characterization revealed the presence of 35 metabolite classes. Broad metabolite classes displayed strong phylogenetic signal, whereas the crude 1H NMR spectr...

Journal of the Brazilian Chemical Society, 2020

Amides have been recognized as potent insecticidal natural products but, despite their variety of... more Amides have been recognized as potent insecticidal natural products but, despite their variety of targets and mechanisms of action, their metabolic fate in insects is virtually unknown. The currently accepted hypothesis is that specialist herbivores are capable of biotransforming xenobiotics rendering them more polar and excretable while generalist insects do not have comparable capacity. The leaves from Piper tuberculatum, rich in insecticide amides, were offered to two insect species found on Piper leaves under natural conditions and also to four generalist grasshoppers in order to compare their capacity of biotransforming xenobiotics. The amides 1-7 were identified in the P. tuberculatum leaves and their corresponding carboxylic acids 8-13 were detected in frass samples of two host insects suggesting that these species promote the amides hydrolysis. The four generalist grasshoppers when offered P. tuberculatum leaves, starved to death after 72 h, indicating a strong antifeedant activity of P. tuberculatum leaves.

Frontiers in Plant Science, 2019

RSC Adv., 2017

First occurrence of all-cishexamethoxy-tetrahydrofuran lignans1aand1b, which are 6.5 kcal mol−1le... more First occurrence of all-cishexamethoxy-tetrahydrofuran lignans1aand1b, which are 6.5 kcal mol−1less stable than the all-transisomer grandisin (2a).

Nature Reviews Chemistry, 2018

Phytochemical variation among plant species is one of the most fascinating and perplexing feature... more Phytochemical variation among plant species is one of the most fascinating and perplexing features of the natural world and has implications for both human health and the functioning of ecosystems. A key area of research on phytochemical variation has focused on insects that feed on plants and the enormous diversity of plant-derived compounds that reduce or deter damage by insects. Empirical studies on the ecology and evolution of these chemically mediated plant-insect interactions have been guided by a long history of theoretical development. However, until recently , such theory was substantially limited by inadequate data, a situation that is rapidly changing as ecologists partner with chemists utilizing the latest technological advances. In this Review , we aim to facilitate the union of ecological theory with modern chemistry by discussing important theoretical frameworks for studying chemical ecology and outlining the steps by which hypotheses on insect-phytochemical interactions can be advanced using current methodologies and statistical approaches. We highlight unique approaches to isolation, synthesis, spectroscopy , metabolomics and genomics relevant to chemical ecology and describe future areas for research that will bring an unprecedented understanding of phytochemical variation.

$Research paper thumbnail of {"__content__"=>"Structure⁻Activity Relationship of Piplartine and Synthetic Analogues against and Cytotoxicity to Mammalian Cells.", "i"=>{"__content__"=>"Schistosoma mansoni"}}$

International journal of molecular sciences, Jan 19, 2018

Schistosomiasis, caused by helminth flatworms of the genus , is an infectious disease mainly asso... more Schistosomiasis, caused by helminth flatworms of the genus , is an infectious disease mainly associated with poverty that affects millions of people worldwide. Since treatment for this disease relies only on the use of praziquantel, there is an urgent need to identify new antischistosomal drugs. Piplartine is an amide alkaloid found in several species (Piperaceae) that exhibits antischistosomal properties. The aim of this study was to evaluate the structure⁻function relationship between piplartine and its five synthetic analogues (19A, 1G, 1M, 14B and 6B) against adult worms, as well as its cytotoxicity to mammalian cells using murine fibroblast (NIH-3T3) and BALB/cN macrophage (J774A.1) cell lines. In addition, density functional theory calculations and in silico analysis were used to predict physicochemical and toxicity parameters. Bioassays revealed that piplartine is active against at low concentrations (5⁻10 µM), but its analogues did not. In contrast, based on 3-(4,5-dim...