Three new indole alkaloids with methyl chanofruticosinates skeletal system, viz., methyl 12-methoxy-N1-decarbomethoxychanofruticosinate, methyl 12-methoxychanofruticosinate and methyl 11,12-dimethoxychanofruticosinate, in addition to methyl 11,12-methylenedioxy-N1-decarbomethoxychanofruticosinate, have been isolated from the leaves of Kopsia flavida Blume. The structures of these three new indole alkaloids were assigned by NMR spectral data using various 2D-techniques.
The plant Andrographis paniculata found throughout Southeast Asia contains Andrographolide 1, a diterpenoid lactone, which has antitumour activities against in vitro and in vivo breast cancer models. In the present study, we report on the synthesis of andrographolide derivatives, 3,19-isopropylideneandrographolide (2), 14-acetyl-3,19-isopropylideneandrographolide (3) and 14-acetylandrographolide (4), and their in vitro antitumour activities against a 2-cell line panel consisting of MCF-7 (breast cancer cell line) and HCT-116 (colon cancer cell line). Compounds 2 and 4 were also screened at the US National Cancer Institute (NCI) for their activities against a panel of 60 human cancer cell lines derived from nine cancer types. Compound 2 was found to be selective towards leukaemia and colon cancer cells, and compound 4 was selective towards leukaemia, ovarian and renal cancer cells at all the dose-response parameters. Compounds 2 and 4 showed non-specific phase of the cell cycle arrest in MCF-7 cells treated at different intervals with different concentrations. NCI's COMPARE and SOM mechanistic analyses indicated that the anticancer activities of these new class of compounds were not similar to that of standard anticancer agents, suggesting novel mechanism(s) of action.
Three benzophenones, 2,6,3',5'-tetrahydroxybenzophenone (1), 3,4,5,3',5'-pentahydroxybenzophenone (3) and 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone (4), as well as a xanthone, 1,3,6-trihydroxy-5-methoxy-7-(3'-methyl-2'-oxo-but-3'-enyl)xanthone (9), were isolated from the twigs of Garcinia cantleyana var. cantleyana. Eight known compounds, 3,4,5,3'-tetrahydroxy benzophenone (2), 1,3,5-trihydroxyxanthone (5), 1,3,8-trihydroxyxanthone (6), 2,4,7-trihydroxyxanthone (7), 1,3,5,7-tetrahydroxyxanthone (8), quercetin, glutin-5-en-3β-ol and friedelin were also isolated. The structures of the compounds were elucidated by spectroscopic methods. The compounds were investigated for their ability to inhibit low-density lipoprotein (LDL) oxidation and platelet aggregation in human whole blood in vitro. Most of the compounds showed strong antioxidant activity with compound 8 showing the highest inhibition with an IC₅₀ value of 0.5 μM, comparable to that of probucol. Among the compounds tested, only compound 4 exhibited strong inhibitory activity against platelet aggregation induced by arachidonic acid (AA), adenosine diphosphate (ADP) and collagen. Compounds 3, 5 and 8 showed selective inhibitory activity on platelet aggregation induced by ADP.
Microalgae lipids and oils are potential candidates for renewable biodiesel. Many microalgae species accumulate a substantial amount of lipids and oils under environmental stresses. However, low growth rate under these adverse conditions account for the decrease in overall biomass productivity which directly influence the oil yield. This study was undertaken to investigate the effect of exogenously added auxin (indole-3-acetic acid; IAA) on the oil content, fatty acid compositions, and the expression of fatty acid biosynthetic genes in Chlorella vulgaris (UMT-M1). Auxin has been shown to regulate growth and metabolite production of several microalgae. Results showed that oil accumulation was highest on days after treatment (DAT)-2 with enriched levels of palmitic (C16:0) and stearic (C18:0) acids, while the linoleic (C18:2) and α-linolenic (C18:3n3) acids levels were markedly reduced by IAA. The elevated levels of saturated fatty acids (C16:0 and C18:0) were consistent with high expression of the β-ketoacyl ACP synthase I (KAS I) gene, while low expression of omega-6 fatty acid desaturase (ω-6 FAD) gene was consistent with low production of C18:2. However, the increment of stearoyl-ACP desaturase (SAD) gene expression upon IAA induction did not coincide with oleic acid (C18:1) production. The expression of omega-3 fatty acid desaturase (ω-3 FAD) gene showed a positive correlation with the synthesis of PUFA and C18:3n3.
Four bisindole alkaloids, viz., 19'(S)-hydroxyconodurine, conodurinine, 19'(S)-hydroxyconoduramine, and 19'(S)-hydroxyervahanine A, in addition to conodurine and ervahanine A, were obtained from the leaf and stem-bark extracts of Tabernaemontana corymbosa. The structures of the new alkaloids were determined using NMR and MS analysis.
Two new venalstonine derivatives, viz., venacarpines A and B, and one new dioxokopsan derivative, kopsorinine, in addition to the kopsifolines A-F, and 11 other known alkaloids, were isolated from a Malayan Kopsia species. The structures of the new alkaloids were determined using NMR and MS analysis.
Six new alkaloids, viz., alstolactone, affinisine oxindole, lagumicine, N(4)-demethylalstonerine, N(4)-demethylalstonerinal, and 10-methoxycathafoline N(4)-oxide, in addition to 36 other known alkaloids, were obtained from the leaf extract of Alstonia angustifolia var. latifolia. The structures of the new alkaloids were determined using NMR and MS analysis.
Four tropical seaweeds, Gracilaria manilaensis Yamamoto & Trono, Ulva reticulata Forsskål, Kappaphycus alvarezii (Doty) L.M.Liao and Turbinaria conoides (J.Agardh) Kützing, collected from various habitats throughout Malaysia, were subjected to temperatures of 40, 35, 30, 25 and 20 °C in the laboratory. An exposure range of 21-38 °C is reported for Malaysian waters. The effect of the temperature exposures on the halocarbon emissions of the seaweeds were determined 4 and 28 h after treatment. The emission rates for a suite of six halocarbons commonly emitted by seaweeds, bromoform (CHBr3), dibromomethane (CH2Br2), diiodomethane (CH2I2), iodomethane (CH3I), dibromochloromethane (CHBr2Cl) and dichlorobromomethane (CHBrCl2), were measured using a cryogenic purge-and-trap sample preparation system coupled to a gas chromatography-mass spectrometry. The emission rate of CHBr3 was the highest of the six halocarbons for all the seaweeds under all the temperatures tested, followed by CH2Br2, and CH2I2. The emission rates were affected by temperature change and exposure duration, but overall responses were unique to each seaweed species. Larger decreases in the emissions of CHBr3, CH2Br2, CH2I2 and CHBr2Cl were found for K. alvarezii and T. conoides after 4 h at 40 °C. In both cases there was a >90% (p
The chemical formation of terpenes in nature is carried out by terpene synthases as the main biocatalysts to guide the carbocation intermediate to form structurally diverse compounds including acyclic, mono- and multiple cyclic products. Despite intensive study of the enzyme active site, the mechanism of specific terpene biosynthesis remains unclear. Here we demonstrate that a single mutation of the amino acid L454G or L454A in the active site of Persicaria minor β-sesquiphellandrene synthase leads to a more promiscuous enzyme that is capable of producing additional hydroxylated sesquiterpenes such as sesquicineole, sesquisabinene hydrate and α-bisabolol. Furthermore, the same L454 residue mutation (L454G or L454A) in the active site also improves the protein homogeneity compared to the wild type protein. Taken together, our results demonstrate that residue Leucine 454 in the active site of β-sesquiphellandrene synthase is important for sesquiterpene product diversity as well as the protein homogeneity in solution.
A total of 20 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia angustiloba, of which two are hitherto unknown. One is an alkaloid of the angustilobine type (angustilobine C), while the other is a bisindole alkaloid angustiphylline, derived from the union of uleine and secovallesamine moieties. The structures of these alkaloids were established using NMR and MS analysis. Angustilobine C showed moderate cytotoxicity towards KB cells.
Four alkaloids comprising two vallesamine, one strychnan, and one pyranopyridine alkaloid, in addition to 32 other known alkaloids were isolated from two Malayan Alstonia species, Alstonia pneumatophora and Alstonia rostrata. The structures of these alkaloids were determined using NMR and MS analyses, and in one instance, confirmed by X-ray diffraction analysis. The nor-6,7-secovallesamine alkaloid, pneumatophorine, is notable for an unusual incorporation of a 3-ethylpyridine moiety in a monoterpenoid indole. The rhazinilam-type alkaloids (rhazinicine, nor-rhazinicine, rhazinal, and rhazinilam) showed strong cytotoxicity toward human KB, HCT-116, MDA-MB-231, and MRC-5 cells, while pneumatophorine, the uleine alkaloid undulifoline, and the strychnan alkaloids, N4-demethylalstogustine and echitamidine, induced concentration dependent relaxation in phenylephrine-precontracted rat aortic rings.
Four tetracyclic oxindole alkaloids, 7(R)- and 7(S)-geissoschizol oxindole (1 and 2), 7(R),16(R)- and 7(S),16(R)-19(E)-isositsirikine oxindole (3 and 4), in addition to a taberpsychine derivative, N(4)-demethyltaberpsychine (5), were isolated from the Malayan Tabernaemontana corymbosa and the structures were established using NMR and MS analysis.
Two seco-tabersonine alkaloids, jerantiphyllines A and B, in addition to a tabersonine hydroxyindolenine, jerantinine H, and a recently reported vincamine alkaloid 7, were isolated from the leaf extract of the Malayan Tabernaemontana corymbosa and the structures were established using NMR and MS analysis. Biomimetic conversion of jerantinines A and E to their respective vincamine and 16-epivincamine derivatives were also carried out.
Six alkaloids belonging to the methyl chanofruticosinate group, viz., prunifolines A-F, in addition to six other known methyl chanofruticosinate alkaloids, were isolated from the leaf extract of Kopsia arborea. The structures were determined using NMR and MS analysis and comparison with known related compounds.
A total of seventeen alkaloids, comprising six macroline (including alstofolinine A, a macroline indole incorporating a butyrolactone ring-E), two ajmaline, one sarpagine, and eight akuammiline alkaloids, were isolated from the stem-bark and leaf extracts of the Malayan Alstonia macrophylla. The structure and relative configurations of these alkaloids were established using NMR, MS and in several instances, confirmed by X-ray diffraction analysis. Six of these alkaloids were effective in reversing multidrug-resistance (MDR) in vincristine-resistant KB cells.
Lumusidines A-D, bisindole alkaloids of the macroline-macroline type, and one of the macroline-pleiocarpamine type, villalstonidine F, were isolated from the stem-bark extract of Alstonia macrophylla (Apocynaceae). The structures and absolute configurations of these alkaloids were established using NMR, MS, and X-ray diffraction analyses.
Fifteen prenylated or geranylated flavanones and flavanonols were isolated from the leaf extracts of different Glycosmis species collected in Thailand and Malaysia. All structures were elucidated by spectroscopic methods, especially 1D and 2D NMR. Six compounds were described for the first time and two were only known so far as synthetic products. The chemotaxonomic significance of flavanoid accumulation within the genus Glycosmis is highlighted.
Two undescribed sesquiterpenoids, namely dysoticans A and B, and three undescribed sesquiterpenoid dimers, namely dysoticans C-E, together with six analogs, were isolated from the stem bark of Dysoxylum parasiticum (Osbeck) Kosterm. (Meliaceae), growing in West Java, Indonesia. Their structures were elucidated based on extensive spectroscopic analysis and theoretical simulations of ECD spectra and 13C NMR shifts. Dysoticans A and B possessed undescribed cadinanes with minor modifications, while C and D featured unprecedented pseudo-sesquiterpenoid dimers through O-ether linkages of cadinanes and guaianes, respectively. Dysotican E was also characterized as the true-sesquiterpenoid dimer featuring eudesmane-germacrene hybrid framework from the Meliaceae family. Furthermore, A-C and E showed moderate activities against the human breast cancer MCF-7 and cervical cancer HeLa cell lines with IC50 values ranging from 22.15 to 45.14 μM. D selectively exhibited significant cytotoxicity against the HeLa cell line with an IC50 value of 13.00 ± 0.13 μM.
Phytochemical study of the fruits of Chisocheton erythrocarpus (Hiern) allowed the identification of eight undescribed limonoids, namely erythrocarpines O - V (1-6, 7a and 7b), along with seven known compounds. The structures of these compounds were elucidated based on spectroscopic and HRMS data, along with electronic circular dichroism to configure the absolute configuration. Erythrocarpines O and P are γ-hydroxybutenolide analogs of mexicanolide-type limonoids while erythrocarpine Q - V are phragmalin-type limonoids possessing a 1,29-oxymethylene bridge with either benzoyl or cinnamoyl moiety in their structures. Mosquito larvicidal activity revealed that crude DCM extract of C. erythrocarpus possessed a good larvicidal effect against Aedes aegypti larvae in 48 h (LC50 = 153.0 ppm). Subsequent larvicidal activity of isolated compounds indicated that erythrocarpine G (10) and 14-deoxyxyloccensin K (11) were responsible for the enhanced larvicidal effect of the extract, reporting LC50 values of 18.55 ppm and 41.16 ppm, respectively. Moreover, residual activity testing of the crude DCM extract revealed that the duration of its larvicidal effects is up to 14 days, where it maintained a 98 % larval mortality throughout the test period, under laboratory conditions.
In a continuation of our study of the Rutaceae, detailed chemical investigation on Micromelum minutum (Rutaceae) collected from Sepilok, Sabah, Malaysia gave four new coumarins. The structures of the coumarins have been fully characterised by spectroscopic methods as 3",4"-dihydrocapnolactone 1, 2',3'-epoxyisocapnolactone 2, 8-hydroxyisocapnolactone-2',3'-diol 3 and 8-hydroxy-3",4"-dihydrocapnolactone-2',3'-diol 4.