Hiroshi Morita

Hoshi University · Department of Pharmacognosy

Four new bisindole alkaloids, cathagines A (1)–D (4) consisting of an aspidosperma and the fused tetracyclic 3-spirooxindole derived from an iboga type skeleton were isolated from the whole plant of Catharanthus roseus. The structures including absolute stereochemistry were elucidated on the basis of 2D NMR data and CD spectra. Cathagine B (2) show...

Previously, we reported that azamollugin, an aza-derivative of mollugin, exhibited potent inhibitory activity on NO production in LPS-stimulated RAW 264.7 cells. Further investigations in this study revealed that azamollugin not only suppressed iNOS gene expression regulated by NF-κB, but also inhibited LPS-induced IFN-β expression, which is known...

A novel trimeric monoterpenoid indole alkaloid, vincarostine A (1) consisting of an aspidosperma-iboga-aspidosperma type skeleton, was isolated from the whole plant of Catharanthus roseus. The structure including absolute stereochemistry was elucidated on the basis of 2D NMR data and CD spectrum. Vincarostine A (1) showed anti-malarial activity.

Oxomollugin is a degraded product of mollugin and was found to be an active compound that inhibits LPS-induced NF-κB activation. In this study, we investigated the inhibitory activity of oxomollugin, focusing on TLR4 signaling pathway, resulting in NF-κB activation. Oxomollugin inhibited the LPS-induced association of essential factors for initial...

A new dimeric indole alkaloid, vincazalidine A consisting of an aspidosperma type and a modified iboga type with 1-azatricyclo ring system consisting of one azepane and two piperidine rings coupled with an oxazolidine ring was isolated from Catharanthus roseus, and the structure including absolute stereochemistry was elucidated on the basis of spec...

Ceramicines are a series of limonoids which were isolated from the barks of Malaysian Chisocheton ceramicus (Meliaceae), and were known to show various biological activity. Six new limonoids, ceramicines U-Z (1-6), with a cyclopentanone[α]phenanthrene ring system with a β-furyl ring at C-17 were isolated from the barks of C. ceramicus. Their struct...

A dimeric indole alkaloid, isovincathicine consisting of an aspidosperma type and modified iboga with C-7-C-20 connection type skeletons was first isolated from Catharanthus roseus, and the structure including stereochemistry was elucidated on the basis of spectroscopic data as well as DP4 statistical analysis. Isovincathicine inhibited cell prolif...

Ceramicines are a series of limonoids that were isolated from the bark of Malaysian Chisocheton ceramicus (Meliaceae) and were known to show various biological activity. Four new limonoids, ceramicines Q-T (1-4) were isolated from the barks of C. ceramicus, and their structures were determined on the basis of the 1D and 2D NMR analyses in combinati...

Previously, we isolated 2R,3S,15R-calofolic acids (CAs) from Calophyllum scriblitifolium bark, which showed vasorelaxant activity on phenylephrine (PE)-precontracted rat aortic rings. Although the effect was suggested to be induced via an extracellular Ca2+-independent manner and mainly acts on vascular smooth muscle, the exact mechanism of action...

Bioactivity guided separation of Chukrasia velutina root methanolic extract led to the isolation of nine new isopimarane diterpenoids, chukranoids A-I (1-9). The absolute configuration was then assigned by comparing the experimental CD spectra and the calculated CD spectra. Chukranoids A-I (1-9) showed moderate antimalarial activity against Plasmod...

Bioactivity-guided separation of the methanol extract of Calophyllum scriblitifolium bark led to the isolation of five new pyranocoumarins, caloforines A–E (1–5) and two new coumarins, caloforines F and G (6 and 7). Their structures were elucidated by 1D and 2D NMR spectroscopy, and their absolute configurations were investigated by a combination o...

The purpose of this study was to evaluate the in vitro cytotoxic activity of two isolated compounds from Voacanga foetida (Blume) Rolfe against the A549 cell line. The in silico study was carried out to predict the cytotoxic mechanism of two isolated compounds (vocangine and vobtusine lactone) and previously reported compound (vobtusine) against pr...

A novel trimeric triterpene, bismoronic ceramicine (1), was isolated from the bark of Chisocheton ceramicus Miq. The structure was elucidated based on spectroscopic data and chemical correlations. Bismoronic ceramicine (1) showed moderate antimalarial activity against Plasmodium falciparum strain 3D7.

Cliniatines A–C (1–3), three new Amaryllidaceae alkaloids, consisting of 2,6-dimetylpyridine and lycorine-type and/or galanthamine-type were isolated from Clivia miniata (Lindl.) Bosse. The structures and absolute configurations of 1–3 were elucidated based on spectroscopic data and chemical correlation. Cliniatines A–C showed moderate inhibitory a...

A new trimeric monoterpenoid indole alkaloid, divaricamine A (1) consisting of a vobasine-vobasine-iboga type skeleton, was isolated from the root of Tabernaemontana divaricata. The structure including absolute stereochemistry was elucidated on the basis of 2D NMR data and CD spectrum. Divaricamine A (1) showed potent anti-malarial activity.

Eight new limonoids, walsogynes H–O (1–8) were isolated from the barks of Walsura chrysogyne, and their structures were determined on the basis of the 1D and 2D NMR data. Walsogynes H–M (1–6) and O (8) were concluded to be 11,12-seco limonoids with a dodecahydro-1H-naphtho[1,8-bc:3,4-c′]difuran skeleton, and walsogyne N (7) to be 11,12-seco limonoi...

Two new bisindole alkaloids, bisnaecarpamines A (1) and B (2), possessing a vobasine-sarpagine type skeleton were isolated from the bark of Tabernaemontana macrocarpa Jack. Their structures were elucidated by extensive spectroscopic methods and chemical correlation. The absolute configurations of compounds 1 and 2 were established using TDDFT-ECD c...

Bioactivity guided separation of Walsura trichostemon stem methanolic extract led to the isolation of four new dammarane (1–4) and two new apotirucallane triterpenoids (5–6), together with one limonoid (7), 11,25-dideacetyltrichostemonate, 12β, 20S, 24R-trihydroxydammar-25-en-3-one and 12β, 20S, 25-trihydroxydammar-23-en-3-one. Compounds 1–7 showed...

Two new bisindole alkaloids, 12′-O-demethyl-vobtusine-5-lactam and isovobtusine-N-oxide (1 and 2), were isolated from the leaves of Voacanga grandifolia, together with two known bisindole alkaloids. Their structures were elucidated on the basis of 1D and 2D NMR data. 1 and 2 showed potent antimalarial activity against Plasmodium falciparum 3D7 and...

A novel Lycopodium alkaloid, complanadine F (1), seco-complanadine A type was isolated from the club moss Lycopodium complanatum. The planar structure and relative configuration were elucidated based on spectroscopic data.

Vobtusine is an aspidosperma-aspidosperma alkaloid isolated from alkaloid DCM base fraction of the bark of Voacanga foetida (Blume) Rolfe (Apocynaceae). In this study, the effect of vobtusine on the cell cycle, apoptosis induction, and Bcl-2 family protein expression were investigated by flow cytometr, DNA fragmentation analysis, and western blotti...

Five new 19-acetoxyingols were isolated from the aerial parts of Euphorbia saudiarabica. They included two uncommon pentacyclic acetoxyingols (1, 2) and two 2,3-diepimers (3, 4), representing the first report of 19-acetoxyingols epimers. Their structures were determined by analysis of extensive 1D and 2D NMR spectroscopic data. The absolute configu...

Three new quassinoids, javanicinols A and B (1 and 2) and 4-keto-(16S)-methoxyjavanicin B (3), together with three known quassinoids (4–6) were isolated from the chloroform-soluble fraction of the methanol extract of the Picrasma javanica wood. The structures of 1–3 were determined by spectroscopic analyses, including 1D and 2D NMR, HRESIMS, and CD...

The article Cycloartane triterpenoid (23R, 24E)-23-acetoxymangiferonic acid inhibited proliferation and migration in B16-F10 melanoma via MITF downregulation caused by inhibition of both β-catenin.

Aim: This study aimed to evaluate the antitumor effects of cyclolinopeptide (CL), which suppresses receptor activator of nuclear factor-κB ligand (RANKL) signalling on giant-cell tumours of the bone (GCTB) cells. Materials and methods: GCTB cell lines were established, and the inhibition of cell growth by CL was evaluated using the water-soluble...

The article Computationally-assisted discovery and structure elucidation of natural products, written by Alfarius Eko Nugroho and Hiroshi Morita, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 15 May 2019 without open access.

Previously, we reported that cyclolinopeptides (CLs) extracted from flaxseed inhibited receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclastogenesis from mouse bone marrow cells in vitro. However, mode of action involved in CLs-inhibited osteoclastogenesis has been yet unknown. Therefore, in this study, we investigated the deta...

Two new sarpagine-type indole alkaloids (1 and 2), together with five known alkaloids; 12-methoxy-4-methylvoachalotine (3), 16-demethoxycarbonylvoacamine (4), isositsirikine (5), affinisine (6), affinine (7), were isolated from the bark of Tabernaemontana macrocarpa Jack. The structures of these alkaloids were determined based on spectroscopic data...

Computer hardware development coupled with the development of quantum chemistry, new computational models and algorithms, and user-friendly interfaces have lowered the barriers to the use of computation in the discovery and structure elucidation of natural products. Consequently, the use of computational chemistry software as a tool to discover and...

The article Ceramicines M–P from Chisocheton ceramicus: isolation and structure–activity relationship study.

Taberniacins A (1) and B (2), new indole alkaloids, were isolated from the stems of Tabernaemontana divaricata (Apocynaceae). Structure elucidation of 1 and 2 was based on spectroscopic methods and total synthesis. Each alkaloid showed vasorelaxant activity against phenylephrine-induced contraction of isolated rat aorta.

Two new bisindole alkaloids, leucophyllinines A (1) and B (2) consisting of eburnane and quebrachamine-type skeletons were isolated from the bark of Leuconotis eugeniifolia, and their structures were elucidated on the basis of spectroscopic data. Leucophyllinines A and B showed antiplasmodial activities against Plasmodium falciparum 3D7.

Picrasma javanica Blume (Simaroubaceae) is a medium-sized tree that is distributed widely in tropical Asia. In our previous study, we isolated quassinoids from P. javanica bark collected in Myanmar, and reported their antiproliferative activities. In our ongoing research for the discovery of bioactive compounds from Myanmar medicinal plants, two ne...

Three new bisindole alkaloids, bisleuconothines B-D (1-3), were isolated from the bark of Leuconotis griffithii. Their structures were elucidated by 1D and 2D NMR spectroscopy and DFT calculations. Bisleuconothine B (1) is the first monoterpene indole alkaloid dimer featuring bridges between both C-16-C-10' and C-2-O-C-9'. All compounds were deemed...

We recently reported that (23R, 24E)-23-acetoxymangiferonic acid (23R-AMA), a cycloartane triterpenoid isolated by activity-guided separation from a methanol extract of Garcinia sp. bark, inhibited melanin production via inhibition of tyrosinase (TYR) expression in the B16-F10 melanoma cell line. Since 23R-AMA also inhibited microphthalmia-associat...

Bioactivity guided separation of Reinwardtiodendron cinereum barks methanol extract led to the isolation of two new onocerane triterpenoids, reinereins A and B (1 and 2), together with three known onocerane triterpenoids. Their structures were elucidated on the basis of NMR spectroscopic data. In vitro cytotoxic activities of the isolated compounds...

A novel class of C38N4Lycopodium alkaloid, hupercumine A (1), consisting of two octahydroquinolines, a decahydroquinoline, and a piperidine, and a new C27N3-type alkaloid, hupercumine B (2), were isolated from Huperzia cunninghamioides (Hayata) Holub. The structures and absolute configurations of 1 and 2 were elucidated on the basis of spectroscopi...

Ceramicines are a series of limonoids which were isolated from the bark of Malaysian Chisocheton ceramicus (Meliaceae) and show various biological activities. Ceramicine B, in particular, has been reported to show a strong lipid droplet accumulation (LDA) inhibitory activity on a mouse pre-adipocyte cell line (MC3T3-G2/PA6). With the purpose of dis...

Two new 3,4-seco-apotirucallane triterpenoids, Apowalsogynes A and B (1 and 2), were isolated from the barks of Walsura chrysogyne, and their structures were determined on the basis of the NMR and CD spectra, and by using the modified Mosher's method. In addition, the cytotoxic activities of 1 and 2 against various cancer cell lines were evaluated.

The ceramicines, a series of limonoids from Chisocheton ceramicus (Meliaceae), were evaluated for anti-melanin deposition activity on α-melanocyte stimulating hormone (α-MSH) and 3-isobutyl-1-methylxanthine (IBMX)-treated B16-F10 melanoma cell, and several ceramicines were found to be active. The structure–activity relationship of ceramicines as an...

Two new phenyl propanoids were extracted from the bark of Cryptocarya bracteolate Gamb., ethyl 3-(2'-hydroxy-3',4',5'-trimethoxyphenyl) propanoate (1) and ethyl 3-(2'-glucosyl-3',4',5'-trimethoxyphenyl)propanoate(2), together with seven known alkaloids, (+)-lirioferine (3), (+)-bracteoline (4), (+)-reticuline (5), (+)-reticulineN-oxide (6), (-)-nor...

Flaxseed (Linum usitatissimum seed) is widely used in food and natural health products. In our search for osteoclast differentiation inhibitors, some cyclic peptides isolated from flaxseed, known as the cyclolinopeptides, were discovered to have osteoclast differentiation inhibition activity. The osteoclast differentiation inhibition activity of cy...

We have previously reported that bisleuconothine A (Bis-A), a novel bisindole alkaloid isolated from Leuconotis griffithii, showed cytostatic activity in several cell lines. In this report, the mechanism of Bis-A-induced cytostatic activity was investigated in detail using A549 cells. Bis-A did not cause apoptosis, as indicated by analysis of annex...

Mollugin, a naphthoquinone derivative, was reported to possess various biological activities such as anti-inflammatory and anti-tumor activity. Mollugin isolated from Rubia tinctorum roots inhibited lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 macrophages. However, mollugin synthesized for further investigation of its anti-in...

isolation and structure elucidation of the new vobasine-iboga type bisindole alkaloid, voacalgine F (I)

An injection molding machine according to the invention includes a motor, a driver circuit that drives the motor; and a rectifying part that supplies electric power to the driver circuit. A regenerative line for regenerative electric power of the motor is connected to the rectifying part in parallel. A converting part and a harmonics component redu...

The leaves of Eucalyptus globulus contain unique macrocarpals consisting of a phrologlucinol and sesquiterpene having an antibacterial activity on oral bacteria and an inhibitory effect on glucosyltransferase (GTase). In this paper, a 60% ethanol extract of E. globulus leaves (extract A) and its EtOAc-soluble fraction (extract B) containing most of...

Two new aromadendrane sesquiterpenoids, dysosesquiflorins A and B (1 and 2), were isolated from Dysoxylum densiflorum bark, and their structures were elucidated on the basis of NMR spectroscopic data. These dysosesquiflorins showed in vitro cytotoxic activity against several cancer cell lines.

A new benzylisoquinoline alkaloid, lincangenine-4-β-D-glucopyranoside (1), has been isolated from the roots of Leontice altaica, together with 5 known alkaloids. Its structure was elucidated on the basis of 1D and 2D NMR data, and chemical means.

A new bisindole alkaloid, voacalgine F (1), has been isolated from the bark of Indonesian Voacanga grandifollia (Miq.) Rolfe. Its structure was elucidated on the basis of 1D and 2D-NMR data analysis.

The compounds (I) and (II) are examined as an inseparable mixture of isomers and are ultimately defined by total synthesis.

Thirteen new triterpenoids, dysotriflorins A–M (1–13), were isolated from Dysoxylum densiflorum barks, and their structures were elucidated on the basis of NMR spectroscopic data and X-ray crystallography. Dysotriflorins A, B, and K–M (1, 2, and 11–13) were concluded to be unique 13,17-secodammarane triterpenoids, and dysotriflorins C–J (3–10) to b...

A new acyclic diterpenoid (1) and a new erythroxan diterpenoid (2), together with 4 erythroxan diterpenoids and 3 triterpenoids, have been isolated from the aerial parts of Fagonia mollis. Their structures were elucidated on the basis of 1D and 2D NMR data. The cytotoxic activity of the isolated compounds was investigated against HL-60 cancer cells...

A novel C16N2-type Lycopodium alkaloid consisting of a quinolizidine with a 6-dimethylaminohexyl side chain, hupermine A (1), was isolated from the club moss of Huperzia phlegmaria, and the structure and relative stereochemistry were elucidated on the basis of spectroscopic data. (c) 2014 Elsevier Ltd. All rights reserved.

Justidrusamides A-D (1-4), four new alkaloids containing 2-aminobenzyl alcohol, succinic acid, and 2,3-dihydroxy-2-(1-hydroxyethyl) butanoic acid skeletons have been isolated from leaves of Justicia gendarussa, and their structures were elucidated using 2D NMR data and chemical means. This is the first report of a 2,3-dihydroxy-2-(1-hydroxyethyl) b...

Four new compounds, 2-hydroxy-6-(12'-hydroxyheptadec-13'(E)-en-1-yl)benzoic acid (1), 2-hydroxy-6-(13'-hydroxyheptadec-1 1'(E)-en-1-yl)benzoic acid (2), 2-hydroxy-6-(10'-hydroxypentadec-11'(E)-en-1 -yl)benzoic acid (3), and 2-hydroxy-6-(11'-hydroxypentadec-9'(E)-en-1-yl)benzoic acid (4) were isolated from the leaves of Ginkgo biloba and the structu...

Previously, we reported the isolation of cassane-type diterpenes, sucutiniranes A-F, from the seeds of Bowdichia nitida. In this study, a series of sucutinirane derivatives was prepared, and their in vitro toxicity in the HL-60 cell line was evaluated. Then the action mechanism of a representative compound that induces cell death was investigated....

In this paper, we construct a nonlinear reduced order model of a plasticization cylinder of injection machines, which has a spatially distributed nonlinear dynamics. First, a distributed parameter model for the overall control system is derived based on the physical laws. Next, we attempt to reduce the model complexity focusing on the specific stru...

Compound (I) exhibits moderate cell growth inhibitory activity.

Four new chromone alkaloids, chrotacumines G-J (1-4), have been isolated from the barks of Dysoxylum acutangulum. Their structures and absolute configurations were elucidated on the basis of NMR and CD data. Chrotacumines G and J (1 and 4) showed osteoclast differentiation inhibitory activity in a dose dependent manner.

Recently people often suffer from unhealthy energy metabolism balance as they tend to take more energy than required. Normally, excess energy taken in is converted into triglyceride and stored in adipocyte as lipid droplets. Recent studies have suggested that irregular accumulation of triglyceride in adipocyte might be a cause of many metabolic dis...

Four new Amaryllidaceae alkaloids (1-4) possessing a homolycorine-type or a crinine-type skeleton have been isolated from the aerial part of Zephyranthes candida, and their structures were elucidated on the basis of spectroscopic data. The stereochemistry was elucidated by combination of NOESY correlations and CD analyses.

Chemical investigation of the flowers of Cassia siamea (Leguminosae), resulted in the isolation of two novel tetracycles connecting 5-(2-hydroxypropyl)benzene-1,3-diol, cassibiphenols A (1) and B (2). The structures were elucidated by analysis of the 1D, 2D NMR, and HRMS spectra. Synthesis of a tetracyclic core of 1 and 2 led to determine the absol...

Five new indole alkaloids, voacalgines A–E (1–5) consisting of a C-mavacurine type of skeleton with 2,3-dihydroxybenzoate moiety, a macroline-type of skeleton, or a macroline-type of skeleton with C6 unit, were isolated from the bark of Voacanga grandifolia. Their relative structures were determined by means of NMR data. Voacalgine A showed moderat...

We derive a mathematical model for an electromagnet inside a molding machine, and propose a novel loop-shaping method of the proportional–integral (PI) controller design for the system based on the generalized KYP (GKYP) lemma. The behavior of the molding machine is difficult to capture by using finite-dimensional models owing to eddy currents spat...

From the methanolic crude extract of Rauvolfia reflexa six indole alkaloids were isolated namely; (1), akuammilan (2), vomilenine (3), isoresrpiline (4), rescinnamine (5), and cantleyine (6). The methanol crude extract showed moderate anticancer activity against MCF-7 and WRL-68 cell lines, although the isolated compounds and dichloromethane crude...

A chemical investigation of the alkaloidal fraction of Dysoxylum acutangulum leaves led to the isolation and characterization of two new chromone alkaloid analogs named chrotacumines E and F (1 and 2, resp.). Structure elucidation of 1 and 2 was achieved by spectroscopic analyses, including 2D-NMR. Both of these alkaloids exhibited modest activitie...

Five new diterpenoids belonging to labdane and isopimarane skeletons, mumic acids A-E (1-5), have been isolated from mumiyo. Their structures and absolute configurations were elucidated on the basis of spectroscopic data and chemical derivatization.

Three new aspidofractinine; N(1)-formylkopsininic acid (1), N(1)-formylkopsininic acid-N(4)-oxide (2), 15-hydroxykopsamine (3), a new aspidospermatan; 14 α-hydroxy-N(4)-methylcondylocarpine (4), and a new akuamiline; singaporentinidine (5) type indole alkaloids were isolated from the roots of Kopsia singapurensis. Their structures were determined o...

The new galloylbergenin (I) is isolated from Bergenia crassifolia together with four known related compounds.

Determination of the absolute configuration (AC) is often a challenging aspect in the structure elucidation of natural products. When chiral compounds possess appropriate chromophore(s), electronic circular dichroism (ECD) may provide a powerful approach to the determination of their absolute configuration. Recently, ECD calculations by time-depend...

Three new terpenoids, opaciniols A-C (1-3), were isolated from the barks of Garcinia opaca, together with malabarica-17,21-dien-3β,14-diol (4) and 13βH-malabarica-14,17,21-trien-3β-ol (5). Their structures were determined on the basis of NMR spectroscopic data. 3 and 4 showed moderate cytotoxicity against HL-60 cells.

Five new cytotoxic limonoids, erythrocarpines A–E (1–5), were isolated from the bark of Chisocheton erythrocarpus Hiern. Chemical structures, stereochemistry, and conformation were fully elucidated and characterized by 2D NMR, MS, and computational methods.

3D QSAR of rhazinilam (1), an alkaloid isolated from Rhazya stricta (Apocynaceae) with an activity involving disassembly of microtubules and its derivatives was investigated by using the comparative molecular field analysis (CoMFA). In an effort to get a better understanding of the correlation between conformation and antitubulin activity of 1, mos...

A novel C16N-type Lycopodium alkaloid consisting of a decahydroquinoline and a cyclohexanone, huperminone A (1), was isolated from the club moss of Huperzia phlegmaria, and the structure and relative stereochemistry were elucidated on the basis of spectroscopic data. This unique C16N-type skeleton lacking in a nitrogen atom may be generated from C1...

Three new limonoids, ceramicines B–D (1–3), have been isolated from the bark of Chisocheton ceramicus. Structures and stereochemistry of 1–3 were fully elucidated and characterized by 2D NMR analysis. Ceramicines exhibited a moderate antiplasmodial activity.

The bark of Cryptocarya crassinervia provided two new phenantrene alkaloids, 2-hydroxyatherosperminine (1) and N-demethyl-2-methoxyatherosperminine (2).

The Meliaceae family of plants has been shown to contain a vast number of compounds with the potential to be developed for medicinal purposes. We have previously reported the isolation of limonoids from a plant in the Meliaceae family named Chisocheton ceramicus. Ceramicine B was identified as an active compound in inhibiting lipid droplets accumul...

Study on chemical constituents from Kopsia singapurensis (Apocynaceae) yielded four new aspidofractinines: Singaporentine A (1), N(1)-formylkopsininic acid (2), N(1)-formylkopsininic acid-N(4)-oxide (3), 15-hydroxykopsamine (4); a new aspidospermatan: 14α-hydroxy-N(4)-methylcondylocarpine (5) and a new akuamiline: singaporentinidine (6) together wi...

In our search for lipid-droplets accumulation (LDA) inhibitors, some ceramicines, a series of limonoids isolated from the barks of Chisocheton ceramicus, were discovered to be active as anti-LDA. Preliminary structure-activity relationships (SAR) of ceramicines as LDA inhibitors based on ceramicines A-L (1-12) and ceramicine B derivatives were desc...