Eight new compounds, including four flavaglines (1 – 4) and four triterpenoids (5 – 8), together with 16 known compounds, were isolated from Aglaia perviridis collected in Vietnam. The new compounds 2 – 4 and seven known rocaglate derivatives (9 – 15) exhibited significant cytotoxicity against the HT-29 cell line. The cytotoxic compounds were further evaluated against a normal colon cell line, CCD-112CoN. In addition, the new compound perviridicin B (2) and four known compounds (9, 11, 12 and 17), showed significant NF-κB (p65) inhibitory activity in an ELISA assay.
Following the primary screening of Vietnamese plant extracts against the HT-29 human colon cancer cell line assay, the branch sample of Linociera cf. ramiflora (Roxb.) Wall. (Oleaceae) (sample A06576; voucher specimen DDS 14374) was selected as a candidate for further study. The methanol extract of this plant sample was subjected to a bioactivity-guided fractionation aiming at the isolation of potential anticancer agents. Liquid-liquid partitions of this extract led to an active chloroform fraction (IC50= 7.7 µg/mL). Further separation of this fraction through successive column chromatography afforded numerous active sub-fractions, from which several new and known lignans and arylglycerol-substituted lignan derivatives together with some aromatic compounds were isolated. The structure determination as well as the antiproliferative and quinone reductase inducting activities of these compounds will be described.
Five new lupane triterpene coumaroyl esters (1 – 5) were isolated from a CHCl3-soluble partition of a methanol extract of Buxus cochinchinensis Pierre ex Gagnep. (Buxaceae) collected in South Vietnam. Isolation work was monitored using human colon cancer cells (HT-29). The structures of the new compounds (1 – 5) were determined on the basis of spectroscopic data interpretation. In addition to the cytotoxicities against HT-29 cells and NF-κB (p65) inhibitory activities in an ELISA assay, all isolates were also evaluated for their in vitro antimalarial and antifungal activities.
Plant samples collected in the Southeast Asian rainforests were subjected to initial screening against the HT-29 human colon cancer cell line, and Podocarpus neriifolius D. Don (Podocarpaceae), obtained from Vietnam, with an IC50 value of 8.2 µg/mL, was selected for further investigation aiming for the discovery of potential anticancer lead agents. Bioactivity-guided purification of the active ethyl acetate fraction (IC50= 4.3 µg/mL) from the dried root sample of P. neriifolius has so far afforded three type-B podolactones, namely, makilactones E (1) and G (2) and inumakilactone A (3), all characterized by the presence of a 7α,8α-epoxy-9(11)-enolide functionality [1 – 3]. Their structures were determined by interpretation of spectroscopic data and comparison with the existing literature [1,2]. In addition, the X-ray crystallography data of 1 was obtained to confirm its absolute configuration. While 3 has shown termiticidal and cytotoxic activity against murine leukemia cells P388 in vitro [1,2], in this study, it exhibited potent activity against HT-29 with an IC50 value of 1.1µM. On the other hand, compounds 1 and 2 were non-cytotoxic in this assay. In this presentation, the isolation and structure determination of these compounds are described as well as the dereplication of additional active sub-fractions, which suggests the presence of different active podolactones and totarane-type diterpenes.
A large amount of a known triterpene, ursolic acid (6 g from 6 kg of the dried plant sample, with a yield of 0.6% w/w), and a known natural phenol, trimethylellagic acid, were isolated and identified from the leaves and twigs of Syzygium corticosum (Lour.) Merr. & L.M. Perry (Myrtaceae) collected in Vietnam. The structures of both compounds were determined by analysis of their ECD, IR, UV, NMR, and mass spectra and by comparison of these spectroscopic data with literature values, and the cytotoxicity was tested against the HT-29 human colon cancer cell line. The known compound, ursolic acid, was found to show activity, and it was regarded as the major cytotoxic principle of Syzygium corticosum. Several new analogues have been synthesized and evaluated, and it was found that both the C-3 hydroxy and the C-28 carboxyl groups play a key role in mediation of cytotoxicity of ursolic acid against HT-29 cells.
Indigofera spicata Forssk. (Leguminosae) has become widespread in tropical and sub-tropical countries as a ground cover plant. In the present investigation, the bioactivity-guided fractionation of a cytotoxic chloroform extract of the flowers, fruits, leaves, and twigs of I. spicata, collected in Vietnam, using the HT-29 human colon cancer, 697 human acute lymphoblastic leukemia, and the Raji human Burkitt's lymphoma cell lines, led to the isolation of seven compounds. Of the isolates, (+)-10-deacetyl-purpurin and (2S)-2,3-dihydrotephroglabrin are new compounds. The compounds, cis-(6aβ,12aβ)-hydroxyrotenone and rotenone, exhibit potent cytotoxicity for 697 and HT-29 cells with IC50 values of less than 1µM. Tephrosin was found to be cytotoxic and cytostatic for 697 cells. Compounds were also tested in a quinone reductase induction assay with tephrosin showing a CD value of 0.4µM. (Support in part by grant P01 CA125066 from the National Cancer Institute, NIH, Bethesda, MD, is acknowledged).
A new sarpagine-type indole alkaloid (1), together with nine known alkaloids (2 – 9), were isolated from the stems of Alstonia angustifolia Wall. ex A. DC. (Apocynaceae) collected in South Vietnam. Compounds 1 – 10 were evaluated for their NF-κB (p65) inhibitory activities against HT-29 cells in an ELISA assay. The new sarpagine alkaloid (1), was found to show significant NF-κB inhibitory activity (ED50= 1.2 µM). Furthermore, all the isolates (1 – 10) were tested in vitro for their antileishmanial activity, and compounds (1 – 4, 6, 8 – 10) were found to show leishmaniacidal activities.
Four new and several known cardiotonic steroids were discovered from Streblus asper Lour. (Moraceae) collected in South Vietnam. The structures of the new compounds were established by analysis of their CD, IR, UV, NMR, and mass spectra, with those of the known compounds being determined by comparison of their spectroscopic data with the literature values. Several of these substances were cytotoxic toward the HT-29 human colon cancer cells, with a known compound, strebloside, found to be potently cytotoxic against the HT-29 cells, showing an IC50 value of 170 nM. A preliminary structure-cytotoxicity-relationship study for strebloside showed that the glycose unit linked at the C-3 position and the C-19 aldehyde residue of this compound both play an important role in mediation of its cytotoxicity, and the activity was retained when the C-4′ hydroxy group of the glycose moiety is modified.
Three new and seven known rotenoids, along with two new isoflavonoids and a known analogue, were isolated from the n-hexane extract of the fruits of Millettia caerulea (Graham) Baker (Fabaceae) collected in Vietnam (sample A06946; voucher specimen DDS-14879). The structures of the new compounds were established by analysis of their ECD, IR, UV, NMR, and mass spectra, with those of the known compounds being determined by comparison of their spectroscopic data with literature values. Several of these compounds were found to be cytotoxic toward the HT-29 human colon cancer cells, among which a known compound, 12β-hydroxyrotenone, was the most potently active, showing an IC50 value of 0.1µM. This same compound was active (IC50 3.1µM), when evaluated in a K-Ras inhibition assay using HT-29 cells.
As part of a P01 collaborative research between the University of Illinois at Chicago and the Ohio State University field expeditions were undertaken in Vietnam from 2004 – 2011 to collect plants for study as potential anticancer agents. The field expeditions resulted in the acquisition of 1,019 primary screening samples, comprising of 445 phytochemically underexplored endemic species. Extracts of 824 samples represented by 398 species were submitted for cytotoxicity (HT-29 and CCD-112CoN) as well as mechanism-based assays (NF-κB p65, proteasome, and MTP inhibition). As a result, 17 new and 42 known compounds with in vitro activity (IC50 < 10 µM) were purified by cytotoxicity-guided fractionation. This research has demonstrated that tropical plants continue to provide numerous chemically diverse secondary metabolites with activity and selectivity for cancer cells.
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