Degree Name

Doctor of Philosophy


Department of Chemistry


The aims of this project were to: 1) assess the efficacy of a combined chemo- and biorational approach involving alkaloid occurrence with antimicrobial medicinal plant use, focussing on plants from Lombok island. Lombok has a large population while herbal medicines are widely used with a diverse range of plant species. 2) Investigate the alkaloid constituents of selected plants including isolation, purification, and characterisation, and structure elucidation. 3) Evaluate antibacterial and antimalarial activities of crude alkaloid extracts and major alkaloid compounds isolated from the plants. 4) Identify compounds as possible new drug leads.

A combined chemo- and bio-rational strategy based on alkaloid content and traditional medicinal plant use was demonstrated to be an effective and efficient approach to finding new biologically active compounds in nature. Several new alkaloids were isolated with some potential for development as antibacterial and antimalarial agents. Some previously known alkaloids were also isolated, and in some cases NMR features not previously reported in the literature are presented.

A new optically active indole alkaloid, lombine (major), and the known alkaloid voacangine (minor), were identified from the bark of Voacanga foetida (Bl.) Rolfe, used ethnomedically for the treatment of wounds, itches, and swellings. The fruits of the plant produced three known alkaloid compounds, coronaridine (major), voacangine, and voacristine, together with the new indole alkaloids mataranine A and B, which were also isolated from Alstonia scholaris R. Br. in this study. Voacristine was found as a major alkaloid together with the minor alkaloid voacangine from the leaves of V. foetida (Bl.) Rolfe. A structural revision for voacristine was also completed.

Initial antibacterial testing of the crude alkaloid extract from V. foetida (Bl.) Rolfe (and fruits) showed activity against both Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli). The new alkaloids lombine (bark) and mataranine A and B (fruits) also exhibited antibacterial activity. Bactericidal activity observed for lombine at a concentration of 0.5 mg/ml against S. aureus and E. coli. At the lower concentration of 0.05 mg/l, it partially inhibited the growth of both S. aureus and E. coli. The crude alkaloid extract from the leaves was found to be active only against S. aureus. Voacristine was considered most likely to be the main active component. These compounds particularly lombine, are thus useful as potential drug leads.

Another new antibacterial agent (LPM-574), a substituted derivative of hodgkinsine, was isolated from Psychotria malayana Jack (leaves). This compound, the structure of which was not completely elucidated, was found to have bacteriostatic potency against S. aureus and E. coli at a concentration of 1.0 mg/ml. The major alkaloid component, hodgkinsine, showed no antibacterial activity at this concentration. However, further structure elucidation and testing are needed for compound LMP-574 before it can be considered as a viable drug lead. Another new indole alkaloid labeled as LPM-186 was isolated as minor compound from this plant.

From the plant Alstonia scholaris (leaves; young trees), used in the treatment of malaria, the new indole alkaloids mataranine A and B were isolated. The crude extract of this plant exhibited antimalarial activity against Plasmodium falciparum, with EC50 values in vitro against antifolate resistant parasites (KI strain) and antifolate sensitive parasites (TM4 strain) of 15.6 μg/ml and 21.0 μ/ml respectively. The new diastereomeric alkaloids mataranine A and B (mixture) had increased potency against KI with an EC50 of 2.6 μg/ml (7.4 μM) and EC50 value of 3.4 p,g/ml (9.7 μM) against the TM4 strain. Thus, either mataranine A or B, or the mixture, could provide useful new leads not only for antimalarial compounds but also for antibacterial agents. Two other new alkaloids, (15S*, 16S*)- losbanine and kotarajine, and the known alkaloids alstonamine and (EAakuammidine, were also isolated from leaves of young trees of A. scholaris. The antimalarial testing of these compounds has not been carried out as yet.

While there is some indication that the plants, Clerodendron calamitosum L. (the leaves were used for the treatment of malaria and wounds) and C. paniculatum (the flowers were used to cure sore eyes), based on their traditional medicinal uses, might contain some new alkaloids, full structure elucidation was not achieved due to the very small quantities available. The crude alkaloid extract from each plant did show some antibacterial activity against E. coli. The crude alkaloid extract from C. calamitosum L. also showed activity against antifolate-resistant Plasmodium falciparum parasites (KI) in vitro and it was found that the major alkaloid, compound Lcc-3, was responsible for the activity.



Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.