Bioactive alkaloids from medicinal plants of Bhutan (original) (raw)

Phytochemical and Biological Activity Studies of the Bhutanese Medicinal Plant Corydalis crispa

the isolation of nine known isoquinoline alkaloids: protopine (1), 13-oxoprotopine (2), 13-oxocryptopine (3), stylopine (4), coreximine (5), rheagenine (6), ochrobirine (7), sibiricine (8) and bicuculline (9), with complete NMR data for 2 and 3 provided here for the first time. Crude extracts exhibited significant anti-inflammatory (p<0.01) activity against TNF-α production in LPS activated THP-1 cells. The acetylcholinesterase inhibitory activity of compounds 2, 4 and 7 and the antiplasmodial activity of compound 5 against P. falciparum strains TM4/8.2 and K1CB1 (multidrug resistant strain) are reported here for the first time. Stylopine (4) did not show antimalarial activity against the K1CB1 strain in contrast to a previous report. This study generated a scientific basis for the use of this plant in Bhutanese traditional medicine, either individually or in combination with other medicinal ingredients to treat a broad range of disorders. This study also identified compound 5 as potential new antimalarial lead compound

Bioactive alkaloids from medicinal plants of Lombok

2002

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 alkalo 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 xi 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. xii F r o m 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 Jig/ml and 21.0 (ig/ml respectively. The new diastereomeric alkaloids mataranine A and B (mixture) had increased potency against KI with an EC50 of 2.6 M-g/ml (7.4 |iM) and EC 50 value of 3.4 p,g/ml (9.7 pM) 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.

Antiplasmodial agents from the Bhutanese medicinal plant Corydalis calliantha

Phytotherapy Research, 2009

The alkaloidal components of the Bhutanese medicinal plant Corydalis calliantha Long, which is used for the treatment of malaria, have been assessed. Four known alkaloids, protopine (1), scoulerine (2), cheilanthifoline (3) and stylopine (4) are reported from this plant for the first time. The protopine alkaloid, protopine, and the tetrahydroprotoberine alkaloid, cheilanthifoline, showed promising in vitro antiplasmodial activities against Plasmodium falciparum, both wild type (TM4) and multidrug resistant (K1) strains with IC50 values in the range of 2.78–4.29 µm. Such activity had not been demonstrated previously for cheilanthifoline. The results thus support, at a molecular level, the clinical use of this plant in the Bhutanese traditional medicine and identified cheilanthifoline as a potential new antimalarial drug lead. Copyright © 2009 John Wiley & Sons, Ltd.

Antimalarial compounds isolated from plants used in traditional medicine

Journal of Pharmacy and Pharmacology, 2009

Objectives This review covers the compounds with antiplasmodial activity isolated from plants published from 2005 to the end of 2008, organized according to their phytochemical classes. Details are given for substances with IC50 values ≤ 11 μM. Key findings Malaria is a major parasitic disease in many tropical and subtropical regions and is responsible for more than 1 million deaths each year in Africa. The rapid spread of resistance encourages the search for new active compounds. Nature and particularly plants used in traditional medicine are a potential source of new antimalarial drugs as they contain molecules with a great variety of structures and pharmacological activities. Summary A large number of antimalarial compounds with a wide variety of structures have been isolated from plants and can play a role in the development of new antimalarial drugs. Ethnopharmacological approaches appear to be a promising way to find plant metabolites that could be used as templates for design...

Alkaloids: A Continuation of Search for Antimalarial Leads

Recently, there has been a resurgence of interests in the isolation and antiplasmodial evaluation of alkaloids from different medicinal plant species. The common heterocyclic moieties associated with bioactivity have continued to appear in the structures of the isolated alkaloids. Interestingly, when these compounds were tested against various strains of Plasmodium falciparum, they proved to demonstrate potent antiplasmodial activities. Herein a number of some alkaloids reported between 2014-2017 have been reviewed in order to serve as an inspiration towards optimizing some leads that could offer new antimalarial drugs.

Cytotoxic and Antimalarial Bisbenzylisoquinoline Alkaloids from Cyclea barbata

Journal of Natural Products, 1993

LAparmnt oj-Pbawnawgmxy, Facufty ofPhmm(lrmti*rlSkcimar, Chukakmgh U n h i t y , Bangkak 10330, Thailand ABsmm.-An alkaloid extract derived from the roots of C y c k barbata demonstrated cytotoxic and antimalarial activities, and five bisbenzylisoquinoline alkaloids, (+ >tetrandrine 111, (-Himacine 121, (+)-thalrugosine 131, (+)-hornoarornoline [4], and (-)-cycleapeltine 151, were isolated as the active principles. The complete and unambiguous assignments of the 'Hand I3C-nmr data of these substances were made by 1D and 2D nmr techniques (COSY, phase-sensitive ROESY, HETCOR, and FLOCK). Journal of Natural Products mol. 56, No. 1 PLANT m m m u . -T h e mots of C. burbata were collected in 1989 in Thailand and were identified by comparison with materials in the Botany Section, Technical Division, Department of Agriculture, Ministry of Agriculture and Cooperatives, Bangkok, Thailand. Voucher specimens are deposited in the E X T R A~I O N AND SEPARATION.-The powdered mots of c. barbata (3.75 kg) were extracted with