Qualitative and quantitative gas chromatography-mass spectrometry analysis of the principal toxic constituents of some South African plants in human biological fluid

In South Africa there are regular cases of human and animal poisoning where plants used in ethnic medicine are suspected to be the source of the poison. This project aims to develop methods for identifying and quantifying the principal toxins of four such plants in human urine. In this way a steppingstone for further research and development on this subject is produced. This project focuses on toxins from four plants that fall into two broad classes of compounds: cardiac glycosides (Acokanthera oppositifolia and Urginea sanguinea) and alkaloids (Boophane disticha and Gloriosa superba). The principal toxic compounds within the respective plants are: acovenoside A, scillaren A, buphanidrine and colchicine. In this study, buphanidrine was isolated from a dichloromethane-methanol plant extract of B. disticha, through the utilisation of multiple chromatographic techniques, and its structure confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. Samples of known analyte concentrations were prepared by spiking blank urine samples with specific amounts of analyte stock solution. Extraction of colchicine and cardiac glycosides from urine was accomplished by solid-phase extraction. The extracted cardiac glycosides were hydrolysed in hydrochloric acid and the reaction products extracted via liquid-liquid extraction. Following extraction, the products of the hydrolysis reaction were silylated for gas chromatography-mass spectrometry analysis. Extracts from urine samples containing colchicine were prepared without a hydrolysis process. Urine samples spiked with buphanidrine were prepared by buffering to alkaline pH, and subsequently conducting a liquid-liquid extraction. The organic phase extracts for both alkaloids were concentrated by evaporation and reconstitution in a small volume of an organic solvent. Both alkaloids were analysed without derivatisation following up-concentration. Response models were generated by duplicate analyses of three batches of each analyte in a de-ionised aqueous solution and urine, respectively. The applicability of the linear response models to the measured data was evaluated for each respective analyte. The relative standard deviation was evaluated to establish the variance in the linear models. The response models, developed for colchicine, acovenoside A and scillaren A, were problematic and further investigated to determine the contributing factors. In the case of colchicine and acovenoside A, the utilisation of log-linear response models was less problematic in describing the trends in the data. In analysing the trends in the processed data, the limits of detection and quantification were calculated statistically for buphanidrine, acovenoside A and colchicine. These were then compared to limits observed in the qualitative analysis of the analytes based on ion ratios. For each analyte five characteristic ion ratios were selected, considering the molecular ion signal area, relative to that of the base peak ion for each analyte. Applying multivariate Gaussian statistical analysis techniques, the correlation of ion ratios and their dependence upon analyte concentration was established. This proved insightful regarding the mechanism of analyte fragmentation. Suggested further work, following this project, should look at factors concerning the optimisation of sample preparation methods, especially the purification via solid-phase extraction. The project provided an opportunity for the investigation of trends in ion ratios, to determine the fundamental limits of identification.Dissertation (MSc (Chemistry))--University of Pretoria, 2021.ChemistryMSc (Chemistry)Unrestricte

Synthesis, Characterization and In Vitro Antitumour Activity of Di-n-Butyl, Tri-n-Butyl and Triphenyltin 3,6-Dioxaheptanoates and 3,6,9-Trioxadecanoates

A series of di- and triorganotin 3,6-dioxaheptanoates and 3,6,9-trioxadecanoates were synthesized and characterized by 1H, 13 and 117Sn NMR, electrospray mass and 119mSn Mössbauer spectroscopy, as well as elemental analysis. Their in vitro antitumour activity against seven tumoural cell lines of human origin, two breast cancers (MCF-7, EVSA-T), a colon carcinoma (WiDr), an ovarian cancer (IGROV), a melanoma (M 19 MEL), a renal cancer (A 498) and a non small cell lung cancer (H 226), is reported. They are characterized by similar inhibition doses ID50 as the analogous di- and triorganotin derivatives of 4-carboxybenzo-15-crown-5 and -18-crown-6 and in some cases by much lower ID50 values than clinically used reference compounds such as doxorubicine and methotrexate

Synthesis, Characterization and Antitumour Activity of Di-n-Butyltin Salicyloxamate

Journal Articleinfo:eu-repo/semantics/publishe

Di-n-Butyl-, Tri-n-Butyl- and Triphenyltin dl-Terebates: Synthesis, Characterization and In Vitro Antitumour Activity

Di-n-butyltin, tri-n-butyltin and triphenyltin terebates were screened against several human tumour cell lines and found comparably or more active than carboplatin, cis-platin, 5-fluorouracil, methotrexate and doxorubicin, some reference compounds used clinically

The Development of Novel Organotin Anti-Tumor Drugs: Structure and Activity

An overview of the development of anti-tumor organotin derivatives in selected classes of compounds is presented and discussed. High to very high in vitro activity has been found, sometimes equaling that of doxorubicin. Solubility in water is an important issue, dominating the in vivo testing of compounds with promising in vitro properties. The cytotoxicity of the compounds was increased by the presence of a bulky group, an active substituent or one or more polar substituents. Polar substituents may also improve the water solubility. Although organotin derivatives constitute a separate class of compounds, the comparison with cisplatin is inevitable. Among the observed toxicities, neurotoxicity, known from platinum cytostatics, and gastrointestinal toxicity, typical for many oncology drugs, have been detected. Further research to develop novel, useful organotin anti-tumor compounds should be carried out

Synthesis, Characterization and Antitumour Activities of Di-n-Butyl- and Dimethyltin D-(+)-Camphorates

Journal Articleinfo:eu-repo/semantics/publishe

Synthesis, Characterization and High In Vitro Antitumour Activity of Novel Triphenyltin Carboxylates

The synthesis and spectral characterization of six novel triphenyltin compounds are described. The in vitro antitumour activity of three of these compounds against two human tumour cell lines, MCF-7, a mammary tumour, and WiDr, a colon carcinoma, was determined. All three compounds are more active than cis-platin, etoposide and doxorubicin against both tumour cell lines. They are as active as mitomycin C against WiDr, but less active against MCF-7

X-Ray Structure and In Vitro Anti-Tumoural Activity of the Dimeric Bis[(2-Phenyl-1,2-Dicarba-Closo-Dodecaborane-1-Carboxylato)-Di-n-Butyltin] Oxide

X-ray diffraction studies reveal the structure of {[(2-C6H5-1,2-C2B10H10-1-COO)Bu2Sn]2O}2, 1, to conform to the common motif found for {[(R′COO)R2Sn]2O}2 compounds. The dimer features a central Bu2Sn2O2 unit (two-fold symmetry) with the two Bu2Sn groups being linked via bridging oxygen atoms, each of which also carries an exocyclic Bu2Sn moiety. The two pairs of exo- and endo-cyclic tin atoms are each linked via an almost symmetrically bridging carboxylate ligand and the two remaining ligands coordinate an exocyclic tin atom only, in the monodentate mode. The in vitro anti-tumour activity of 1, determined against a variety of cell lines, is compared with those of the corresponding 2-methylcarboranylacetate, derivative 2, and with clinically used compounds

Synthesis, Characterization and In vitro Antitumour Activity of Novel Organotin Derivatives of 1,2- and 1,7-Dicarba-Closo-dodecaboranes

Several organotin derivatives of 1,2- and 1,7-dicarba-closo-dodecaboranes were synthesized and characterized by 119Sn Mössbauer, 1H, 13C and 119Sn NMR spectroscopy. Their antitumour activities in vitro against cancerous cell lines of human origin are reported