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.
Enterobacter cloacae is a versatile bacterial species inhabiting a wide variety of niches and is capable of metabolising a wide variety of substances as energy resources. The fermentation culture of this bacterial species has successfully yielded one new compound, Rimboxa (1) and three known compounds, i.e. indole-3-carboxaldehyde (2), indole-3-acetic acid (3) and 3,4-di-t-butylaniline (4). Rimboxa (1) is shown to possess the 1,2-oxathiolane core structure. 3,4-Di-t-butylaniline (4) is isolated for the first time from a natural resource. These compounds were isolated and characterised using extensive chromatographic and spectroscopic methods, and were subjected to cytotoxicity evaluations.
Four new bisindoles of the vobasine-iboga type, conodiparines A-D were obtained from Tabernaemontana corymbosa which showed appreciable activity in reversing resistance in vincristine-resistant KB cells.
Seven new indole alkaloids (1-7) comprising four vobasine, two tacaman, and one corynanthe-tryptamine bisindole alkaloid were isolated from the stem-bark extract of a Malayan Tabernaemontana. Two of the new vobasine alkaloids (1, 3), as well as 16-epivobasine (15) and 16-epivobasenal (17), showed appreciable cytotoxicity toward KB cells (IC50 ca. 5 μg/mL). The structure of the known Tabernaemontana alkaloid tronoharine (8) was revised based on newly acquired NMR data, as well as X-ray diffraction analysis.
Six new indole alkaloids, viz., cononusine (1, a rare example of an iboga-pyrrolidone conjugate), ervaluteine (2), vincamajicine (3), tacamonidine (4), 6-oxoibogaine (5), and N(4)-chloromethylnorfluorocurarine chloride (6), and two new vobasinyl-iboga bisindole alkaloids, ervatensines A (7) and B (8), in addition to other known alkaloids, were isolated from the stem-bark extract of the Malayan Tabernaemontana corymbosa. The structures of these alkaloids were established on the basis of NMR and MS analyses and, in one instance (7), confirmed by X-ray diffraction analysis. Vincamajicine (3) showed appreciable activity in reversing multidrug resistance in vincristine-resistant KB cells (IC50 2.62 μM), while ervatensines A (7) and B (8) and two other known bisindoles displayed pronounced in vitro growth inhibitory activity against human KB cells (IC50 < 2 μM). Compounds 7 and 8 also showed good growth inhibitory activity against A549, MCF-7, MDA-468, HCT-116, and HT-29 cells (IC50 0.70-4.19 μM). Cell cycle and annexin V-FITC apoptosis assays indicated that compounds 7 and 8 inhibited proliferation of HCT-116 and MDA-468 cells, evoking apoptotic and necrotic cell death.
Violacein, violet pigment produced by Chromobacterium violaceum, has attracted much attention recently due to its pharmacological properties including antibacterial activity. The present study investigated possible antibacterial mode of action of violacein from C. violaceum UTM5 against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) strains. Violet fraction was obtained by cultivating C. violaceum UTM5 in liquid pineapple waste medium, extracted, and fractionated using ethyl acetate and vacuum liquid chromatography technique. Violacein was quantified as major compound in violet fraction using HPLC analysis. Violet fraction displayed bacteriostatic activity against S. aureus ATCC 29213 and methicillin-resistant S. aureus ATCC 43300 with minimum inhibitory concentration (MIC) of 3.9 μg/mL. Fluorescence dyes for membrane damage and scanning electron microscopic analysis confirmed the inhibitory effect by disruption on membrane integrity, morphological alternations, and rupture of the cell membranes of both strains. Transmission electron microscopic analysis showed membrane damage, mesosome formation, and leakage of intracellular constituents of both bacterial strains. Mode of action of violet fraction on the cell membrane integrity of both strains was shown by release of protein, K+, and extracellular adenosine 5'-triphosphate (ATP) with 110.5 μg/mL, 2.34 μg/mL, and 87.24 ng/μL, respectively, at 48 h of incubation. Violet fraction was toxic to human embryonic kidney (HEK293) and human fetal lung fibroblast (IMR90) cell lines with LC50 value of 0.998 ± 0.058 and 0.387 ± 0.002 μg/mL, respectively. Thus, violet fraction showed a strong antibacterial property by disrupting the membrane integrity of S. aureus and MRSA strains. This is the first report on the possible mode of antibacterial action of violet fraction from C. violaceum UTM5 on S. aureus and MRSA strains.
Two new heteroyohimbine-type oxindole alkaloids, rauniticine-allo-oxindole B and rauniticinic-allo acid B, have been successfully isolated from the stems extract of Malaysian Uncaria longiflora var. pteropoda. The structures of the two new alkaloids were determined by spectroscopic analysis.
Two new monoterpenoid indole alkaloids, alstoscholactine (1) and alstolaxepine (2), were isolated from Alstonia scholaris. Compound 1 represents a rearranged stemmadenine alkaloid with an unprecedented C-6-C-19 connectivity, whereas compound 2 represents a 6,7- seco-angustilobine B-type alkaloid incorporating a rare γ-lactone-bridged oxepane ring system. Their structures and absolute configurations were determined by spectroscopic analyses. Compound 1 was successfully semisynthesized from 19 E-vallesamine. Compound 2 induced marked vasorelaxation in rat isolated aortic rings precontracted with phenylephrine.