Prenylated acetophenones from Melicope obscura and Melicope obtusifolia ssp. obtusifolia var. arborea and their distribution in Rutaceae

Four prenylated acetophenones 2,6-dihydroxy-4-geranyloxyacetophenone (1), 4-geranyloxy-2,6,β-trihydroxyacetophenone (2), 2,6-dihydroxy-4-geranyloxy-3-prenylacetophenone (3), and 4-geranyloxy-3-prenyl-2,6,β-trihydroxyacetophenone (4) have for the first time been isolated from Melicope obscura (1 and 2) and Melicope obtusifolia ssp. obtusifolia var. arborea (3 and 4). The distribution of prenylated acetophenones in Rutaceae is reviewed and the results, including the new records, indicate that prenylated acetophenones are valuable as chemotaxonomic markers for the subfamily Rutoideae, tribe Xanthoxyleae sensu Engler.     

Three new jacaranone derivatives from the aerial parts of Senecio chrysanoides DC. with their cytotoxic activity

Three new jacaranone derivatives, namely, (1R)-ethyl 1-hydroxy-4-oxo-2-cyclohexenylacetate (1), (1R, 6S)-ethyl 6-ethoxy-1-hydroxy-4-oxo-2-cyclohexenylacetate (2) and (1R, 6R)-ethyl 6-ethoxy-1-hydroxy-4-oxo-2-cyclohexenylacetate (3), along with a known jacaranone derivative, ethyl 1-hydroxy-4-oxocyclohexylacetate (4) were isolated from the aerial parts of Senecio chrysanoides DC.. Their structures were elucidated by spectroscopic methods, optical rotation calculations and CD analyses. All the isolated compounds were evaluated for their cytotoxicity against three human cancer cell lines in vitro. Compound 2 exhibited moderate inhibitory effects against these cancer cell lines.     

Monohydroxycarotenoids from diphenylamine-inhibited cultures of Rhodospirillum rubrum

The monohydroxycarotenoids formed by diphenylamine-inhibited cultures of Rhodospirillum rubrum have been investigated. Nine have been isolated and identified as 1-hydroxy-1,2-dihydrophytofluene (1), 1-Hydroxy-1,2,7′,8′,11′,12′-hexahydrolycopene (2), chloroxanthin (3), 1-methoxy-1′-hydroxy-1,2,1′,2′-tetrahydrophytofluene (4a), 1′-hydroxy-3,4,1′,2′,11′,12′-hexahydrospheroidene (5, 1′-hydroxy-3,4,1′,2′-tetrahydrospheroidene (6, 1′-hydroxy 1′,2′-dihydrospheroidene (7), rhodovibrin (8a) and monodeme thylated spirilloxanthin (9). 4a, 5 and 6 are novel carotenoids, and a definite structure has been assigned to 2 for the first time; the structure of 1 has been amended. The possible role of these carotenoids in spirilloxanthin biosynthesis is discussed.     

Chemical constituents from the fresh flower buds of Musa nana and their chemotaxonomic significance

Phytochemical study on the fresh flower of Musa nana Lour. provided seventeen known compounds including two alkaloids, 3-(hydroxyacetyl)-indole (1), bi-indol-3-yl (2), two terpenoids, 5-[(1R)-1-hydroxy-2,6,6-trimethyl-4-oxo-2-cyclohexen-1-yl]-3-methyl-, (2Z, 4E) −2, 4-pentadienoic acid (Valdes), 5, 6(S), 7, 7a(R)-tetrahydro-6-hydroxy-4,4-dimethyl-2(4H)-benzofuranone (4), seven phenols (5–11), three phenylphenalenones, 2-hydroxy-4-(4-methoxyphenyl)-1H-phenalen-1-one (12), 2-methoxy-9-phenyl-1H-phenalen-1-one (13), 2-methoxy-9-(4-methoxyphenyl)-1H-phenalen-1-one (14), and three lipids (15–17). In the present study, all the compounds were isolated for the first time from the species M. nana. Ten compounds including 1-8 and 15-16 have never been previously encountered in the Musaceae family. Furthermore, the chemotaxonomic significance of these isolates was also discussed.     

Biotransformation of capsaicin by Penicillium janthinellum AS 3.510

Biocatalysis of capsaicin (1) was performed by Penicillium janthinellum AS 3.510. Nine metabolites including four new compounds were afforded, and their structures were elucidated as (8S)-trans-8-hydroxy-8-hydroxymethyl-N-vanillyl-6-nonenamide (2), 6-hydroxy-8-methyl-N-vanillyl-7-nonenamide (3), trans-8-methoxy-8-methyl-N-vanillyl-6-nonenamide (4), 6-methoxy-8-methyl-N-vanillyl-7-nonenamide (5), dihydrocapsaicin (6), ω-1-hydroxydihydrocapsaicin (7), ω-1-hydroxycapsaicin (8), ω-hydroxycapsaicin (9), N-(4-hydroxy-3-methoxybenzyl)-5-[3-(propan-2-yl)oxiran-2-yl]pentanamide (10) by 1D and 2D NMR and HRESIMS spectra. The biotransformation processes include hydroxylation, methylation, reduction, and epoxylation.     

5-Hydroxyindole-type alkaloids,as Candida albicans isocitrate lyase inhibitors,from the tropical sponge Hyrtios sp.

Chemical investigations of the tropical marine sponge Hyrtios sp. have resulted in the isolation of a new alkaloid, 1-carboxy-6-hydroxy-3,4-dihydro-β-carboline (1) together with the known metabolites, 6-hydroxy-3,4-dihydro-1-oxo-β-carboline (2), 5-hydroxy-1H-indole-3-carboxylic acid methyl ester (3), serotonin (4), hyrtiosin A (5), 5-hydroxyindole-3-carbaldehyde (6), and hyrtiosin B (7). Their structures were elucidated on the basis of mass spectrometry and detailed 2D NMR spectroscopic data. Hyrtiosin B (7) displayed a potent inhibitory activity against isocitrate lyase (ICL) of Candida albicans with an IC₅₀ value of 89.0 μM.     

Metabolism of 5β-pregnane-3,20-dione and 3β-hydroxy-5β-pregnan-20-one by Digitalis suspension cultures

Digitalis purpurea normal callus suspension culture is capable of metabolizing 5β-pregnane-3,20-dione (1) to 3β-hydroxy-5β-pregnan-20-one (2), 3α-hydroxy-5β-pregnan-20-one (3), 3β-hydroxy-5β-pregnan-20-one glucoside (7) and 3α-hydroxy-5β-pregnan-20-one glucoside (8). Digitalis purpurea habituated callus suspension culture is also capable of metabolizing 1 to 2, 3, 5β-pregnane-3β,20β-diol (5), (7), (8), 5β-pregnane-3β,20α-diol monoglucoside (9) and 5β-pregnane-3α,20α-diol monoglucoside (11). Furthermore, it was observed that 3β-hydroxy-5β-pregnan-20-one (2) is converted to 7, 9 and 11 by both suspension cultures. At the same time, 1, 3, 5 and 8 were detected in normal callus, while 5β-pregnane-3β,20α-diol (4) and 5β-pregnane-3β,20β-diol monoglucoside (10) were present in the habituated callus culture.     

Difuranonaphthoquinones from Plumbago zeylanica roots

The naphthoquinones, lapachol (1), plumbagin (2), 2-isopropenyl-9-methoxy-1,8-di-oxa-dicyclopenta[b,g]naphthalene-4,10-dione (3), 9-hydroxy-2-isopropenyl-1,8-dioxa-dicyclopenta[b,g]naphthalene-4,10-dione (4), 2-(1-hydroxy-1-methyl-ethyl)-9-methoxy-1,8-dioxa-dicyclopenta[b,g]naphthalene-4,10-dione (5) and 5,7-dihydroxy-8-methoxy-2-methyl-1,4-naphthoquinone (6) were isolated isolated from roots of Plumbago zeylanica. The new constituents (3–5) in addition to known compounds (1, 2 and 6) were characterized by spectral analysis (UV, IR, 1D & 2D NMR and MS).     

The site of inhibition of mitochondrial electron transfer by coenzyme Q analogues.

The effects of 33 quinone derivatives on mitochondrial electron transfer in yeast were examined. Twenty-two of the compounds were also tested for their effects on the growth of yeast cells. Four strong inhibitors of electron transfer were identified: 5-n-undecyl-6-hydroxy-4, 7-dioxobenzothiazole, 7-ω-cyclohexyloctyl-6-hydroxy-5,8-quinolinequinone, 7-n-hexadecyl-mercapto-6-hydroxy-5, 8-quinolinequinone, and 3-n-dodecylmercapto-2-hydroxy-1, 4-naphthoquinone. They inhibit the growth of yeast with ethanol as an energy source, but not when glucose is the energy source. The NADH oxidase activity of isolated mitochondria is 50% inhibited by these quinone derivatives at about 10^?8m, or 0.5 μmol/g mitochondrial protein; 1000-fold higher concentrations do not affect electron transfer from NADH or succinate to coenzyme Q₂. The effects of the inhibitors on cytochrome spectra indicate that they block electron transfer between cytochromes b and c₁. A possible antagonism between these compounds and coenzyme Q at a site between cytochromes b and C₁ is discussed in terms of Mitchell's “protonmotive Q cycle” hypothesis (Mitchell, P. (1976) J. Theor. Biol. 62, 327–367). 6-β-naphthylmercapto-5-chloro-2,3-dimethoxy-1,4-benzoquinone inhibits electron transfer between succinate and coenzyme Q₂ or phenazine methosulfate, suggesting a site in the succinate-coenzyme Q reductase complex with a different quinone specificity from that of the site in the cytochrome bc₁ complex. Seven of the quinone derivatives inhibit growth on both glucose and ethanol media, indicating that their effect is not the result of inhibition of respiration.     

Acylflavonoid C-glycosides from Eleusine coracana

Chromatographic fractionation of the methanolic extract of the shoots of Eleusine coracana led to the identification of three novel acylflavonoid glycosides, 6″-O-3-hydroxy-3-methylglutaroylorientin (1), 6″-O-malonylvitexin (2), and 4″-O-3-hydroxy-3-methylglutaroylvitexin (3) as well as five known flavonoid glycosides, orientin (4), isoorientin (5), vitexin (6), isovitexin (7), and 6″-O-3-hydroxy-3-methylglutaroylvitexin (8). The structures of these compounds were established on the basis of NMR and mass spectral data.     

Microbial transformations of (−)-α- and (+)-β-thujone by fungi of Absidia species

The microbial transformations of (−)-α- and (+)-β-thujone (1a and 1b) in cultures of Absidia species: Absidia coerulea AM93, Absidia glauca AM254 and Absidia cylindrospora AM336 were studied. The biotransformations of (−)-α-thujone (1a), by these fungi strains, afforded mixtures of 4-hydroxy- and 7-hydroxy-α-thujone (2 and 3). Aforementioned fungi strains were also able to hydroxylate of (+)-β-thujone at C-7 position. Only A. glauca AM254 transformed 1b to 8-hydroxy-β-thujone (7) and (2S)-2-hydroxyneoisothujol (6). The (4R)-4-hydroxyisothujole (5) was identified as one of the major metabolite of (+)-β-thujone (1b) in culture of A. cylindrospora AM336. This strain was also able to introduce hydroxy group to C-4 position in 1b without reduction of carbonyl group at C-3. The absolute configuration of all chiral centers of new (4R)-4-hydroxyisothujol (5) and (2S)-2-hydroxyneoisothujol (6) were established taking into account the configuration of (+)-β-thujone (1b) and their spectral data.     

Two tetrahydroisoquinoline alkaloids from the fruit of Averrhoa carambola

The fruit of Averrhoa carambola, commonly known as star fruit or carambola, is popular in Southeast Asia and China. Two new tetrahydroisoquinoline alkaloids, (1R*,3S*)-1-(5-hydroxymethylfuran-2-yl)-3-carboxy-6-hydroxy-8-methoxyl-1,2,3,4-tetrahydroisoquinoline (1) and (1S*,3S*)-1-methyl-3-carboxy-6-hydroxy-8-methyoxyl-1,2,3,4-tetrahydroisoquinoline (2), were isolated from the fruit, along with vanillic acid (3), ferulic acid (4), 8,9,10-trihydroxythymol (5), and arjunolic acid (6). Their structures were elucidated by spectroscopic method. Compounds 1, 2, and 5 showed weak ferric reducing antioxidant potency (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity.     

Phytochemical investigation of Millettia dorwardi Coll. et Hemsl

The first phytochemical investigation on the vine stems of Millettia dorwardi Coll. et Hemsl led to the isolation of ten flavonoids (isoafrormosin 1, formononetin 2, afrormosin 3, padmakastein 4, liquiritigenin 5, 4H-1-Benzopyran-4-one,7-hydroxy-5,8-dimethoxy-3-(4-methoxyphenyl)-isoflavone 6, 4H-1-Benzopyran-4-one,7-hydroxy-3-(3-hydroxy-5-methoxyphenyl)-6-methoxy 8, 4H-1-Benzopyran-4-one,6-methoxy-3-(4-methoxyphenyl)-6,4′-dimethoxyisoflavone 9, irisolidone 10, prunetin 11), one heterocycle (5-5′-dibuthoxy-2-2′-bifuran 7) and one new isoflavone glycoside (4H-1-Benzopyran-4-one,5-hydroxymethyl-3-(4-methoxyphenyl)-6-β-d-glucopyranoside-isoflavone 12). Their structures were determined by extensive analysis of their spectroscopic data. Among them, compounds 4, 6–10, 12 were for the first time isolated from this genus. The chemotaxonomic importance of these compounds was also summarized.     

Two new carene-type monoterpenes from aerial parts of Ageratina adenophora

Two new carene-type monoterpenes, (1α,6α,7α)-8-hydroxy-2-carene-10-oic acid (1) and (1α,6α)-10-hydroxy-3-carene-2-one (2), were isolated from the aerial parts of Ageratina adenophora, together with a known monoterpene, (−)-isochaminic acid (3). The new structures were elucidated on the basis of extensive spectroscopic analysis, including MS, 1D and 2D NMR techniques. Compound 3 was isolated from A. adenophora for the first time. Compounds 2 and 3 were found to show anti-fungal activity against spore germination of Magnaporthe grisea with IC₅₀ values 0.623 and 0.503 mM, respectively.     

Microbial transformation of bavachin by Absidia coerulea

Microbial transformation of bavachin (1), one of the major bioactive components of Psoralea corylifolia L., was performed by using Absidia coerulea. Three oxidized metabolites were obtained in the biotransformation of 1, and their structures were elucidated as bavachinone A (2), (2S)-4′-hydroxy-6,7-[(R)-2-(1-hydroxy-1-methylethyl)-2,3-dihydrofurano]flavanone (3), and (2S)-4′,7-dihydroxy-6-(2,3-dihydroxy-3-methylbutyl)flavanone (4) based on the spectroscopic analyses. Among them, metabolites 3 and 4 were new compounds. The biotransformation study suggested that 1 was fully oxidized to its metabolites within 5 days. Thus, biotransformation by A. coerulea can be used as a promising method for oxidation of bavachin.     

Diarylpentanoids from Diplomorpha canescens and Diplomorpha ganpi

Two new α-hydroxy ketone type diarylpentanoids, diplomorphanone A, 2(S)-hydroxy-1-(4-hydroxyphenyl)-5-phenyl-1-pentanone (1) and diplomorphanone B, 2(R)-hydroxy-1,5-diphenyl-1-pentanone (2) were isolated from aerial parts of Diplomorpha canescens (Meisn.) C.A. Meyer and roots of Diplomorpha ganpi (Sieb. et Zucc.) Nakai, respectively. Nine known compounds including diarylpentanoids (3–6), phenylpropanoid derivatives (7–9), (+)-afzelechin (10) and apiosylskimmin (11) were also isolated for the first time from D. ganpi. Structures of these compounds were elucidated on the basis of spectroscopic data.     

Mycochromone and mycoxanthone: Two new metabolites from Mycosphaerella rosigena

Two new metabolites, dimethyl 2-(2-ethenyl-5-hydroxy-4H-1-benzopyran-4-onyl-3)-malonate (mycochromone 1a) and methyl 2-methoxy-8-hydroxy-9-oxo-9H-xanthene-1-carboxylate (mycoxanthone 6a), have been isolated and identified from the mycelium of Mycosphaerella rosigena grown on potato-agar.     

Design,synthesis, molecular docking and biological activity evaluation of some novel indole derivatives as potent anticancer active agents and apoptosis inducers

Reaction of 5-morphilinosulfonylisatin (1) with acetophenones (2a–e) afforded 3-hydroxy-3-substituted-2-oxoindoles 3a-e, when treated with acetic acid the expected 3-phenacylidene-2-oxoindoles 4a-d and 4-hydroxy-5′-(morpholinosulfonyl) spiro [chromene-2, 3′-indolin]-2′-one 6 were obtained. Isatin derivative (1) was stirred with cyano derivatives to produce the arylidines (7a-c), while under reflux condition, it gave pyrrolo[2,3–b]indoles (8, 9). Moreover, istain (1) reacted with pyrazolo-5-one or 3-substituted phenol in presence of malononitrile to afford spiroxindole derivatives (10a,b) and (11a,b). Also, compounds (10a,b) and (11a,b) were obtained through cyclization of (7a) with pyrazolo-5-one or 3-substituted phenol. The obtained compounds were identified by IR, ¹H NMR, ¹³C NMR and elemental analysis. Anticancer activity against three cancer cell lines (HepG-2, HCT-116 and MCF-7) were evaluated using sulforhodamine B assay method. Compounds 4b, 4c, 7a, 7c and 9 showed broad spectrum anticancer activity on the three tested cell lines with IC₅₀ values less than 10 µM. Cell cycle analysis was performed for the most promising derivatives, compounds 4b and 7c arrested HepG-2 cells at G2-M phase, while compounds 7a and 9 accumulated cells at G0-G1 phase, all of them induced apoptosis at priG1 phase in the range of (11.32–19.17%). Additionally compounds 4b, 7a and 9 showed more potent activity against EGFR than Lapatinib, their IC₅₀ values are from 0.019 to 0.026 µM while IC₅₀ of Lapatinib is 0.028 µM. Molecular docking studies were conducted to investigate the binding mode, amino acid interactions and free binding energy of these potent derivatives.     

Norlignans from Pouzolzia occidentalis

Two structurally interesting new norlignans named 2-hydroxy-4-[4-hydroxyphenyl-(4-hydroxy-3-methoxybenzyl)]-3-(3,5-dihydroxyphenyl)tetrahydrofuran (1) (pouzolignan A), and 1,4-dihydroxy-3-[4-hydroxyphenyl-(4-hydroxy-3-methoxybenzyl)]-2-(3,5-dihydroxyphenyl)butane (2) (pouzolignan B), were isolated from the EtOAc fraction of the methanol extract of Pouzolzia occidentalis. Compound 3, the methyl ether of 1, most likely an artifact, was also isolated. The overall structures and relative stereochemistry were elucidated largely by analysis of 1D and 2D NMR spectral data.     

Microbial oxygenation of dialkylbenzenes (I)

The use of the microorganism Sporotrichum sulfurescens (ATCC 7159) to oxygenate organic molecules has been extended to several dialkylbenzenes. Oxygenation of 1,4-di-t-butylbenzene (1) gave 4-t-butyl(1-hydroxy-2-methyl)isopropylbenzene (2) and 1,4-di-(1-hydroxy-2-methyl)isopropylbenzene (3); of 1,4-diisopropylbenzene (4) gave (R,R)-1,4-di-(1-hydroxy)isopropylbenzene (5); of 1,3-diisopropylbenzene (6) gave 1,3-di-(2-hydroxy)isopropylbenzene (7), 3-(1-hydroxy)isopropyl-(2-hydroxy)isopropylbenzene (8), and 1,3-di-(1-hydroxy)isopropylbenzene (9); and of p-isobutylisopropylbenzene (20) gave 1-(p-2-hydroxyisopropylphenyl)-2-methylpropan-2-ol (15) and 1-(p-1-hydroxyisopropylphenyl)-2-methylpropan-2-ol (16). Monohydroxydialkylbenzenes also served as useful substrates in this reaction as suggested by the fact that 2 is an intermediate in the formation of 3 from 1. Oxygenation of 1-(p-isopropylphenyl)-2-methylpropan-2-ol (14), conveniently prepared from 2-(p-isopropylphenyl)propene (12) via oxygenative isomerization with thallium trinitrate to 13 followed by addition of methyl magnesium bromide, gave 15 and 16. Oxygenation of 2-(p-isobutylphenyl)propan-2-ol (18) gave 15, 2-(p-isobutylphenyl)-propan-1,2-diol (21), and 1-(p-2-hydroxyisopropylphenyl)-2-methylpropan-3-ol (22). Compound 16, obtained from substrate 14, was converted to (2R)-2-[4-(2-hydroxy-2-methylpropyl)phenyl]propionic acid (11), the enantiomer of a metabolite of the antiinflammatory agent, 2-(4-i-butyl)phenylpropionic acid (10).