The n-butyramido, isobutyramido, benzamido, and furancarboxamido functions profoundly modulate the electronics of the stilbene olefinic and NH groups and the corresponding radical cations in ways that influence the efficiency of the cyclization due presumably to conformational and stereoelectronic factors. For example, isobutyramido- stilbene undergoes FeCl(3) promoted cyclization to produce only indoline, while n-butyramidostilbene, under the same conditions, produces both indoline and bisindoline.
Our ongoing investigations on the stem bark of Mesua beccariana afforded a novel cyclodione coumarin, beccamarin, together with two known xanthones, mesuarianone, mesuasinone, two anthraquinones, 4-methoxy-1,3,5-trihydroxy-anthraquinone and 2,5-dihydroxy-1,3,4-trimethoxyanthraquinone and one coumarin, mammea A/AB. The structures were elucidated by 1D and 2D NMR and MS techniques.
Phytochemical investigation of Beilschmiedia alloiophylla has resulted in the isolation of one new alkaloid, 2-hydroxy-9-methoxyaporphine (1), and ten known natural products, laurotetanine (2), liriodenine (3), boldine (4), secoboldine (5), isoboldine (6), asimilobine (7), oreobeiline (8), 6-epioreobeiline (9), β-amyrone (10), and (S)-3-methoxynordomesticine (11). Chemical studies on the bark of B. kunstleri afforded compounds 2 and 4 along with one bisbenzylisoquinoline alkaloid, N-dimethylphyllocryptine (12). Structures of compounds 1-12 were elucidated on the basis of spectroscopic methods. All of these isolates were evaluated for their anti-acetylcholinesterase (AChE), anti-α-glucosidase, anti-leishmanial and anti-fungal activities. Compounds 1-12 exhibited strong to moderate bioactivities in aforementioned bioassays.
1'-(S)-1'-Acetoxychavicol acetate (ACA) isolated from the Malaysian ethno-medicinal plant Alpinia conchigera Griff. was investigated for its potential as an anticancer drug. In this communication, we describe the cytotoxic and apoptotic properties of ACA on five human tumour cell lines. Data from MTT cell viability assays indicated that ACA induced both time- and dose-dependent cytotoxicity on all tumour cell lines tested and had no adverse cytotoxic effects on normal cells. Total mortality of the entire tumour cell population was achieved within 30 hrs when treated with ACA at 40.0 µM concentration. Flow cytometric analysis for annexin-V and PI dual staining demonstrated that cell death occurred via apoptosis, followed by secondary necrosis. The apoptotic effects of ACA were confirmed via the DNA fragmentation assay, in which consistent laddering of genomic DNA was observed for all tumour cell lines after a 24 hrs post-treatment period at the IC(50) concentration of ACA. A cell cycle analysis using PI staining also demonstrated that ACA induced cell cycle arrest at the G(0)/G(1) phase, corresponding to oral tumour cell lines. In conclusion, ACA exhibits enormous potential for future development as a chemotherapeutic drug against various malignancies.
17-O-acetylacuminolide (AA), a diterpenoid labdane, was isolated for the first time from the plant species Neouvaria foetida. The anti-inflammatory effects of this compound were studied both in vitro and in vivo.
Dichloromethane root extract of Rennellia elliptica Korth. showed strong inhibition of Plasmodium falciparum growth in vitro with an IC₅₀ value of 4.04 µg/mL. A phytochemical study of the dichloromethane root extract has led to the isolation and characterization of a new anthraquinone, 1,2-dimethoxy-6-methyl-9,10-anthraquinone (1), and ten known anthraquinones: 1-hydroxy-2-methoxy-6-methyl-9,10-anthraquinone (2), nordamnacanthal (3), 2-formyl-3-hydroxy-9,10-anthraquinone (4), damnacanthal (5), lucidin-ω-methyl ether (6), 3-hydroxy-2-methyl-9,10-anthraquinone (7), rubiadin (8), 3-hydroxy-2-methoxy-6-methyl-9,10-anthraquinone (9), rubiadin-1-methyl ether (10) and 3-hydroxy-2-hydroxymethyl-9,10-anthraquinone (11). Structural elucidation of all compounds was accomplished by modern spectroscopic methods, notably 1D and 2D NMR, IR, UV and HREIMS. The new anthraquinone 1, 2-formyl-3-hydroxy-9,10-anthraquinone (4) and 3-hydroxy-2-methyl-9,10-anthraquinone (7) possess strong antiplasmodial activity, with IC₅₀ values of 1.10, 0.63 and 0.34 µM, respectively.
In this study, the apoptotic mechanism and combinatorial chemotherapeutic effects of the cytotoxic phenylpropanoid compound 1'S-1'-acetoxyeugenol acetate (AEA), extracted from rhizomes of the Malaysian ethnomedicinal plant Alpinia conchigera Griff. (Zingiberaceae), on MCF-7 human breast cancer cells were investigated for the first time. Data from cytotoxic and apoptotic assays such as live and dead and poly-(ADP-ribose) polymerase cleavage assays indicated that AEA was able to induce apoptosis in MCF-7 cells, but not in normal human mammary epithelial cells. A microarray global gene expression analysis of MCF-7 cells, treated with AEA, suggested that the induction of tumor cell death through apoptosis was modulated through dysregulation of the nuclear factor-kappaB (NF-κB) pathway, as shown by the reduced expression of various κB-regulated gene targets. Consequent to this, western blot analysis of proteins corresponding to the NF-κB pathway indicated that AEA inhibited phosphorylation levels of the inhibitor of κB-kinase complex, resulting in the elimination of apoptotic resistance originating from NF-κB activation. This AEA-based apoptotic modulation was elucidated for the first time in this study, and gave rise to the proposal of an NF-κB model termed the 'Switching/Alternating Model.' In addition to this, AEA was also found to synergistically enhance the proapoptotic effects of paclitaxel, when used in combination with MCF-7 cells, presumably by a chemosensitizing role. Therefore, it was concluded that AEA isolated from the Malaysian tropical ginger (A. conchigera) served as a very promising candidate for further in-vivo development in animal models and in subsequent clinical trials involving patients with breast-related malignancies.
Medicinal plants containing active natural compounds have been used as an alternative treatment for cancer patients in many parts of the world especially in Asia (Itharat et al. 2004). In this report, we describe the cytotoxic and apoptotic properties of 1'S-1'-acetoxyeugenol acetate (AEA), an analogue of 1'S-1'-acetoxychavicol acetate (ACA), isolated from the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) on human breast cancer cells. Data from MTT cell viability assays indicated that AEA induced both time- and dose-dependent cytotoxicity with an IC(50) value of 14.0 μM within 36 h of treatment on MCF-7 cells, but not in HMEC normal control cells. Both annexin V-FITC/PI flow cytometric analysis and DNA fragmentation assays confirmed that AEA induced cell death via apoptosis. AEA was also found to induce cell cycle arrest in MCF-7 cells at the G(0)/G(1) phase with no adverse cell cycle arrest effects on HMEC normal control cells. It was concluded that AEA isolated from the Malaysian tropical ginger represents a potential chemotherapeutic agent against human breast cancer cells with higher cytotoxicity potency than its analogue, ACA.
A significant acetylcholinesterase (AChE) inhibitory activity was observed for the hexane extract from the bark of Mesua elegans (Clusiaceae). Thus, the hexane extract was subjected to chemical investigation, which led to the isolation of nine 4-phenylcoumarins, in which three are new; mesuagenin A (1), mesuagenin C (3), mesuagenin D (4) and one new natural product; mesuagenin B (2). The structures of the isolated compounds were characterized by spectroscopic data interpretation, especially 1D and 2D NMR. Four compounds showed significant AChE inhibitory activity, with mesuagenin B (2) being the most potent (IC(50)=0.7μM).
The title compound, systematic name 9-isopropyl-idene-2,6-dimethyl-11-oxatricyclo-[6.2.1.0(1,5)]undec-6-en-8-ol, C(15)H(22)O(2), which crystallizes with two mol-ecules of similar conformation in the asymmetric unit, features three fused rings, two of which are five-membered and the third six-membered. Of the two five-membered rings, the one with an O atom has a distinct envelope shape (with the O atom representing the flap). The six-membered ring is also envelope-shaped as it shares a common O atom with the five-membered ring. In the crystal, the two independent mol-ecules are linked by a pair of O-H⋯O hydrogen bonds, generating a dimer.
Dunaliine A (1), a new amino diketone, has been isolated from the leaves of Desmos dunalii together with four known dihydrochalcones: 2',4-dihydroxy-4',6'-dimethoxy-3',5'-dimethyldihydrochalcone (2), 2',4-dihydroxy-4',6'-dimethoxydihydrochalcone (3), 2',4-dihydroxy-4',5',6'-trimethoxydihydrochalcone (4) and 2',4-dihydroxy-5'-methyl-4',6'-dimethoxydihydrochalcone (5). The structures of these compounds were established notably by spectral analysis (1D- and 2D- (1)H, (13)C NMR), UV, IR and HRMS.
The stem bark of Phoebe grandis afforded one new oxoproaporphine; (-)-grandine A (1), along with six known isoquinoline alkaloids: (-)-8,9-dihydrolinearisine (2), boldine, norboldine, lauformine, scortechiniine A and scortechiniine B. In addition to that of the new compound, complete 1H- and 13C-NMR data of the tetrahydroproaporphine (-)-8,9-dihydrolinearisine (2) is also reported. The alkaloids' structures were elucidated primarily by means of high field 1D- and 2D-NMR and HRMS spectral data.
A new bisindole alkaloid, bisnicalaterine A (1), consisting of two vobasine-type skeletons, and 3-epivobasinol (2) and 3-O-methylepivobasinol (3), with vobasine-type skeletons, were isolated from the leaves of Hunteria zeylanica, and their structures were elucidated on the basis of spectroscopic data and chemical correlation. Bisnicalaterine A showed moderate cytotoxicity against various human cancer cell lines.
The mol-ecule of accanthomine A, C(15)H(13)N(5), is approximately planar, with the indolyl fused-ring and the pyrimidyl ring being twisted by 31.7 (1)° The amino group of the five-membered ring is an intramolecular hydrogen-bond donor to a nitro-gen acceptor of the pyrimide ring. The amino group of the pyrimide ring is a hydrogen-bond donor to the N atoms of adjacent mol-ecules. These hydrogen-bonding inter-actions give rise to a layered network with a 4.8(2) topology.
The bark of Cryptocarya crassinervia provided two new phenantrene alkaloids, 2-hydroxyatherosperminine (1) and N-demethyl-2-methoxyatherosperminine (2).
The phytochemical study of the bark of Malaysian Phoebe scortechinii (Lauraceae) has resulted in the isolation and identification of two new proaporphine alkaloids; (+)-scortechiniine A (1) and (+)-scortechiniine B (2) together with two known proaporphines; (-)-hexahydromecambrine A (3), (-)-norhexahydromecambrine A (4), and one aporphine; norboldine (5). Structural elucidations of these alkaloids were performed using spectroscopic methods especially 1D and 2D (1)H and (13)C NMR.
The title mol-ecule, C(22)H(16)N(2)O(4), is a 2,2'-disubstituted biphenyl whose phenyl-ene rings are rotated by 66.5 (1)° so as to avoid repulsion by the substituents. Only one of the two amide -NH- fragments engages in hydrogen bonding, and this inter-acts with the amido -C(=O)- acceptor of an inversion-related mol-ecule to generate a hydrogen-bonded dimer.
In the title mol-ecule, C(25)H(19)NO(2), the furyl ring is twisted by 46.3 (1)° with respect to the phenyl-ene ring bearing the amido group. In the stilbene unit, the two phenyl-ene rings (i.e. the rings connected through the -CH=CH- fragment) are twisted by 59.2 (1)°; in the biphenyl-ene unit, the two benzene rings are twisted by 35.5 (1)°. In the crystal structure, mol-ecules are linked by an N-H⋯O(amido) hydrogen bond into a zigzag chain running along the c axis.
The leaves of the Phoebe scortechinii (Gamb.) Kochummen Comb. Nov. (Lauraceae), afforded one new proaporphine-tryptamine dimer; (-)-phoebescortechiniine (1), along with two known ones; phoebegrandine A and phoebegrandine B. The proaporphine, tetrahydropronuciferine (2), was isolated for the first time as a natural product. The alkaloids were elucidated primarily by means of high field NMR and HRMS.
The asymmetric unit of the title compound, C(29)H(50)O(2), contains two mol-ecules; one mol-ecule is linked to the other by two O-H⋯O hydrogen bonds, whereas only one of the hydr-oxy groups of the second mol-ecule is involved in hydrogen bonding. This gives rise to a chain that runs along the a axis of the monoclinic unit cell.