ABSTRACT
Examination of the EtOH extract of the leaves of the Malayan Tabernaemontana corymbosa resulted in the isolation of four new (1-4) and two known bisindole alkaloids (5, 6) of the Aspidosperma- Aspidosperma type. The structures of these alkaloids were determined based on analysis of the spectroscopic data (NMR and HRESIMS). X-ray diffraction analyses of the related bisindole alkaloids conophylline (5) and conophyllinine (6) established the absolute configurations. Treatment of the bisindole alkaloid conophylline (5) with benzeneselenic anhydride gave, in addition to the known bisindole polyervinine (7) previously isolated from another Malayan Tabernaemontana, another bisindole product, 8, an isolable tautomer of 7. X-ray diffraction analyses yielded the absolute configurations of both bisindoles and in addition showed that polyervinine (7) exists primarily as the neutral dione structure. The bisindoles (1-8) and the related conophylline-type bisindoles (9-13) showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, A549, HT-29, and HCT 116 cells, with IC50 values for the active compounds in the 0.01-5 µM range.
Subject(s)
Aspidosperma/chemistry , Cell Proliferation/drug effects , Indole Alkaloids/pharmacology , Tabernaemontana/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Indole Alkaloids/chemistry , Molecular Structure , Spectrum Analysis/methodsABSTRACT
Examination of the EtOH extract of the Malayan Alstonia penangiana resulted in the isolation of 10 new alkaloids, comprising two ajmaline (1, 2), four macroline oxindole (3-6), and four macroline-akuammiline bisindole alkaloids (7-10). The structures of these alkaloids were determined based on analysis of the spectroscopic data and, in the case of the oxindole 6 and the bisindole alkaloid 7, also confirmed by X-ray diffraction analysis. The bisindole alkaloids 7 and 8 showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, HCT 116, and A549 cells with IC50 values in the 0.3-8.3 µM range.
Subject(s)
Ajmaline/chemistry , Alkaloids/chemistry , Alstonia/chemistry , Cytotoxins/chemistry , Oxindoles/chemistry , A549 Cells , Antineoplastic Agents, Phytogenic/chemistry , Cell Line, Tumor , Crystallography, X-Ray/methods , Drug Screening Assays, Antitumor/methods , HCT116 Cells , HT29 Cells , Humans , KB Cells , MCF-7 Cells , PC-3 Cells , Vincristine/chemistryABSTRACT
While, Aflatoxin B1 (AFB1), deoxynivalenol (DON) and zearalenone (ZEN) are the most prevalent mycotoxins co-existing in grain products and animal feeds, little is known about their combinatorial toxicities on aquatic life-forms. We studied the individual and combined effects of these mycotoxins in a fish cell line (BF-2) and zebrafish larvae (wild-type and transgenic). The types of interactions in mycotoxins combinations on cell viability were determined by using Chou-Talalay model. Induction of oxidative stress pathway in mycotoxins-exposed BF-2 cells was assessed using high content screening (HCS). Mycotoxin-exposed wild-type zebrafish larvae were examined for mortality and morphological abnormalities and transgenic zebrafish larvae (expressing DsRed in the liver) were imaged using HCS and examined for liver abnormalities. Results showed that the cytotoxicity of mycotoxins in a decreasing order was AFB1>DON>ZEN, however, the highest mortality rate and liver damage in zebrafish were observed for AFB1 followed by ZEN. AFB1+DON and AFB1+ZEN synergistically enhanced the toxic effects on BF-2 cells and zebrafish while DON+ZEN showed antagonism. Interestingly, in the tertiary combination, the synergism seen at lower individual concentrations of mycotoxins progressively turned to an overall antagonism at higher doses. The results provide a scientific basis for the necessity to consider co-exposure when formulating risk-management strategies.
Subject(s)
Aflatoxin B1/toxicity , Trichothecenes/toxicity , Water Pollutants, Chemical/toxicity , Zearalenone/toxicity , Zebrafish/growth & development , Animal Feed , Animals , Animals, Genetically Modified , Cell Line , Cell Survival/drug effects , Larva/drug effects , Larva/genetics , Larva/metabolism , Liver/drug effects , Liver/metabolism , Zebrafish/genetics , Zebrafish/metabolismABSTRACT
Although building constructions are a recurring part of urbanization, the health risk of particulate matters (PM) originating from such activities have seldom been subjected to detailed studies. We sought to characterize the relative risk of air borne PM collected from different heights (ground and top floor) of a building adjacent to a building under early phase of construction. We determined the physico-chemical properties such as size and shape, elemental composition and surface charge of the PM. The oxidative stress dependent cytotoxic and pro-inflammatory responses were assessed in BEAS-2B and RAW 264.7 cell lines using high-content-screening platforms. In comparison to top floor, the total mass of PM collected from ground floor was two-three folds higher and the mass fraction was dominated by PM20-35. Elemental analysis showed abundance of Si, Al, K, Ca and Fe in bigger PM while for PM0.25-0.5 it was mostly constituted by C and crystals rich in S and K. PM caused NFκB activation, secretion of pro-inflammatory cytokines and cytotoxicity wherein PM0.25-0.5 was the most potent among the tested PM. Estimated exposure level and lung burden together with the data on hazard potential were used for developing a MATLAB based risk-assessment model which suggested that the potential for health risk is relatively higher at the ground floor. Our studies demonstrated differences in, relative abundance of PM, their physicochemical and biological properties collected from different heights adjacent to a construction site and showed that relative health risk is higher at the ground floor.
