Chisocheton is one of the genera of the family Meliaceae and consists of ca. 53 species; the distribution of most of those are confined to the Indo-Malay region. Species of broader geographic distribution have undergone extensive phytochemical investigations. Previous phytochemical investigations of this genus resulted in the isolation of mainly limonoids, apotirucallane, tirucallane, and dammarane triterpenes. Reported bioactivities of the isolated compounds include cytotoxic, anti-inflammatory, antifungal, antimalarial, antimycobacterial, antifeedant, and lipid droplet inhibitory activities. Aside from chemistry and biological activities, this review also deals briefly with botany, distribution, and uses of various species of this genus.
Photodynamic therapy (PDT) is a medical treatment that involves the irradiation of an administered photosensitizing drug with light of a particular wavelength to activate the photosensitizer to kill abnormal cells. To date, only a small number of photosensitizers have been clinically approved for PDT, and researchers continue to look for new molecules that have more desirable properties for clinical applications. Natural products have long been important sources of pharmaceuticals, and there is a great potential for discovery of novel chemotypes from under-explored biodiversities in the world. The objective of this study is to mine the terrestrial plants in Sarawak, Borneo Island, for new photosensitizers for PDT. In a screening program from 2004 to 2008, we prepared and studied 2,400 extracts from 888 plants for their photosensitizing activities. This report details the bioprospecting process, preparation and testing of extracts, analysis of the active samples, fractionation of four samples, and isolation and characterization of photosensitizers.
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 activities as tyrosinase inhibitors with 29.2 and 25.8% inhibition at 100 μg/ml, respectively.
In our screening program for new photosensitizers from the Malaysian biodiversity, we found five pheophorbide-related compounds from the leaves and stems of Aglaonema simplex. Detailed spectroscopic analyses showed that compounds 1-3 and 5 are pheophorbide and hydroxy pheophorbide derivatives of chlorophyll a and b. Compound 4, identified as 15(1)-hydroxypurpurin-7-lactone ethyl methyl diester, was isolated for the first time from the Araceae family. An MTT-based short-term survival assay showed that all five compounds exhibit moderate-to-strong photocytotoxic activities towards human leukemia (HL60) and two oral squamous carcinoma cell lines (HSC-2 and HSC-3). Compounds 4 and 5 showed the strongest photocytotoxicities, with IC(50) values of 0.30-0.41 muM (Table 2). Compounds 1-3 with Et chains at C(17(3)) were less photocytotoxic than the parent pheophorbide a (5).
Six new indole alkaloids, viz., (3S)-3-cyanocoronaridine (2), (3S)-3-cyanoisovoacangine (3), conolobine A (5), conolobine B (6), conolidine (7), and (3R/3S)-3-ethoxyvoacangine (8), in addition to 36 known ones, were obtained from the stem-bark extract of the Malayan Tabernaemontana divaricata. The structures were determined by NMR and MS analysis. The CN-substituted alkaloids showed appreciable cytotoxicity towards the KB human oral epidermoid carcinoma cell-line.
As a part of our chemical studies on Malaysian medicinal plants, five Malaysian plant species were evaluated by cytotoxicity assays using P388 murine leukemia cells. Since Acalypha siamensis exhibited the strongest growth inhibition, its constituents were studied as the object of search for bioactive materials. A novel tetraterpene, acalyphaser A (1), was isolated in the course of the purification. Its structure was elucidated on the basis of 1D- and 2D-NMR techniques, and mass spectrometry.
Analysis by GC and GC/MS of the essential oil obtained from Malaysian Curcuma mangga Val. & Zijp (Zingiberaceae) rhizomes allowed the identification of 97 constituents, comprising 89.5% of the total oil composition. The major compounds were identified as myrcene (1; 46.5%) and β-pinene (2; 14.6%). The chemical composition of this and additional 13 oils obtained from selected Curcuma L. taxa were compared using multivariate statistical analyses (agglomerative hierarchical cluster analysis and principal component analysis). The results of the statistical analyses of this particular data set pointed out that 1 could be potentially used as a valuable infrageneric chemotaxonomical marker for C. mangga. Moreover, it seems that C. mangga, C. xanthorrhiza Roxb., and C. longa L. are, with respect to the volatile secondary metabolites, closely related. In addition, comparison of the essential oil profiles revealed a potential influence of the environmental (geographical) factors, alongside with the genetic ones, on the production of volatile secondary metabolites in Curcuma taxa.
In our screening program for new photosensitizers from Malaysian biodiversity for photodynamic therapy (PDT) of cancer, MeOH extracts of ten terrestrial plants from Cameron Highlands in Pahang, Peninsular Malaysia, were tested. In a short-term 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, 20 μg/ml each of these extracts were incubated in a pro-myelocytic leukemia cell-line, HL60, with or without irradiation with 9.6 J/cm(2) of a broad spectrum light. Three samples, Labisia longistyla, Dichroa febrifuga, and Piper penangense, were photocytotoxic by having at least twofold lower cell viability when irradiated compared to the unirradiated assay. The extract of the leaves of Piper penangense, a shrub belonging to the family Piperaceae and widely distributed in the tropical and subtropical regions in the world, was subsequently subjected to bioassay-guided fractionation using standard chromatography methods. Eight derivatives of pheophorbide-a and -b were identified from the fractions that exhibited strong photocytotoxicity. By spectroscopic analysis, these compounds were identified as pheophorbide-a methyl ester (1), (R,S)-13(2) -hydroxypheophorbide-a methyl ester (2 and 3), pheophorbide-b methyl ester (4), 13(2) -hydroxypheophorbide-b methyl ester (5), 15(2) -hydroxylactone pheophorbide-a methyl ester (6), 15(2) -methoxylactone pheophorbide-a methyl ester (7), 15(2) -methoxylactone pheophorbide-b methyl ester (8).
Two poorly studied, morphologically allied Alpinia species endemic to Borneo, viz., A. ligulata and A. nieuwenhuizii, were investigated here for their rhizome essential oil. The oil compositions and antimicrobial activities were compared with those of A. galanga, a better known plant. A fair number of compounds were identified in the oils by GC-FID and GC/MS analyses, with large differences in the oil composition between the three species. The rhizome oil of A. galanga was rich in 1,8-cineole (29.8%), while those of A. ligulata and A. nieuwenhuizii were both found to be extremely rich in (E)-methyl cinnamate (36.4 and 67.8%, resp.). The three oils were screened for their antimicrobial activity against three Gram-positive and three Gram-negative bacteria and two fungal species. The efficiency of growth inhibition of Staphylococcus aureus var. aureus was found to decline in the order of A. nieuwenhuizii>A. ligulata ∼ A. galanga, while that of Escherichia coli decreased in the order of A. galanga>A. nieuwenhuzii ∼ A. ligulata. Only the A. galanga oil inhibited the other bacteria and the fungi tested.
The essential oils from the leaves and rhizomes of Alpinia pahangensis Ridl., collected from Pahang, Peninsular Malaysia, were obtained by hydrodistillation, and their chemical compositions were determined by GC and GC/MS analyses. The major components of the rhizome oil were γ-selinene (11.60%), β-pinene (10.87%), (E,E)-farnesyl acetate (8.65%), and α-terpineol (6.38%), while those of the leaf oil were β-pinene (39.61%), α-pinene (7.55%), and limonene (4.89%). The investigation of the antimicrobial activity of the essential oils using the broth microdilution technique revealed that the rhizome oil of A. pahangensis inhibited five Staphylococcus aureus strains with minimum inhibitory concentration (MIC) values between 0.08 and 0.31 μg/μl, and four selected fungi with MIC values between 1.25 and 2.50 μg/μl.
Inflammatory bowel disease (IBD) is the main risk factor for developing colorectal cancer which is common in patients of all ages. 5-Aminosalicylic acid (5-ASA), structurally related to the salicylates, is highly active in the treatment of IBD with minor side effects. In this study, the synthesis of galactose and fructose esters of 5-ASA was planned to evaluate the role of glycoconjugation on the bioactivity of the parent drug. The antibacterial activity of the new compounds were evaluated against two Gram-negative and two Gram-positive species of bacteria, with a notable effect observed against Staphylococcus aureus and Escherichia coli in comparisons with the 5-ASA. Cytotoxicity testing over HT-29 and 3T3 cell lines indicated that the toxicity of the new products against normal cells was significantly reduced compared with the original drug, whereas their activity against cancerous cells was slightly decreased. The anti-inflammatory activity test in RAW264.7 macrophage cells indicated that the inhibition of nitric oxide by both of the monosaccharide conjugated derivatives was slightly improved in comparison with the non-conjugated drug.
Bioassay-guided fractionation of a MeOH extract of tubers of Coleus tuberosus afforded the active anti-tumor-promoting compounds identified as the triterpenoid 2alpha,3beta-dihydroxyolean-12-en-28-oic acid (maslinic acid; CT2) and a phytosterol mixture (CT1). CT1 consists of stigmasterol (32%), beta-sitosterol (40.3%), and campesterol (27.7%) as determined by capillary gas chromatography. CT1 and CT2 showed very strong anti-tumor-promoting activities at IC(50) 0.7 microg/ml and 0.1 microg/ml, respectively, in a convenient, short-term in vitro assay, i.e., the inhibition of Epstein-Barr virus (EBV) activation induced by phorbol 12-myristate 13-acetate (PMA) and sodium butyrate. We report for the first time the anti-tumor-promoting activity of 2alpha,3beta-dihydroxyolean-12-en-28-oic acid and show that a mixture of stigmasterol, beta-sitosterol, and campesterol is more potent than the individual components in inhibiting tumor-promoting activity.
Trichoderma spp. are regularly found as a constituent of the mycoflora of many soils and are noted for their antagonistic activity against bacteria and other fungi. This latter property is the basis for the widespread interest in their use in the biological control of soil-borne fungal plant pathogens. This antagonism is partly based on their ability to produce an impressive inventory of secondary metabolites. An important group of bioactive metabolites produced by Trichoderma spp. are the non-ribosomal peptides (NRPs), especially the peptaibols. A virulent antagonistic strain, T. asperellum, which had been used in biological control strategies in Malaysia and previously examined for mycolytic enzyme production, has been studied for its potential for peptaibol production. The present research demonstrated the ability of T. asperellum to produce at least two metabolites which were identified as acid trichotoxin 1704E (Ac-Aib-Gly-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Ala-Ala-Aib-Pro-Leu-Aib-Iva-Glu-Vol) and neutral trichotoxin 1717A (Ac-Aib-Gly-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Ala-Aib-Aib-Pro-Leu-Aib-Iva-Gln-Vol). Addition of free Aib to the culture medium enhanced the production of trichotoxins. Biological activity of these substances was investigated against Bacillus stearothermophilus. The general characteristics of peptaibols, also found in the trichotoxins, include the presence of high proportions of the uncommon amino acid Aib, the protection of the N- and C-termini by an acetyl group and reduction of the C-terminus to 2-amino alcohols, respectively, amphipathy and microheterogeneity.
The inhibition of carbohydrate-hydrolyzing enzymes in human digestive organs is crucial in controlling blood sugar levels, which is important in treating type 2 diabetes. In the current study, pahangensin A (1), a bis-labdanic diterpene characterized previously in the rhizomes of Alpinia pahangensis Ridl., was identified as an active dual inhibitor for α-amylase (IC50 =114.80 μm) and α-glucosidase (IC50 =153.87 μm). This is the first report on the dual α-amylase and α-glucosidase inhibitory activities of a bis-labdanic diterpene. The Lineweaver-Burk plots of compound 1 indicate that it is a mixed-type inhibitor with regard to both enzymes. Based on molecular docking studies, compound 1 docked in a non-active site of both enzymes. The dual inhibitory activity of compound 1 makes it a suitable natural alternative in the treatment of type 2 diabetes.