Bioactive alkaloids from medicinal plants of Bhutan

摘要: Natural products had been indispensably used by many cultures and traditions in folklore medicines for thousands of years. These traditional cater to about 85% the world population their primary health care needs. have intensively explored also bioactive pharmacophores modern pharmaceutical companies. In fact they are skeletal framework 60% drugs that available today. Of these, 80% antibacterial 90% antimalarial natural derivatives. One interesting secondary metabolite groups which provides these potent drug leads alkaloids. Owing broad range bioactivities, bioprospecting undertaken countries. this study, on molecular basis medicine Bhutan, particularly those with potential antimicrobial components, four alkaloid positive medicinal plants, i.e. Aconitum orochryseum Stapf, Corydalis gerdae Fedde, Rununculus brotherusi Freyn an Australian naturalized plant Tribulus terrestris Linn, but were selected phytochemical analysis. Bhutanese use (whole parts) treatment bilious fever or high related bile disorders including cold flu, (liver), caused malaria, snake bites treating blood infections. is malaria Ranunculus (aerial wounds, pus, infections as antipyretics. (fruit) arthritis, kidney diseases a diuretic. Though failed give any alkaloids, number new well known alkaloids isolated from gerdae. Three hetisane type diterpenoid named orochrine, 2-O-acetylorochrine, lingshinaline, together two atisinium chloride virescenine six other unidentified orochryseum. The structures elucidated ¹H-NMR, gCOSY, gNOESY, TOCSY, ¹³C-NMR, DEPT, gHSQC gHMBC spectral data analysis. Atisinium chloride, major plant, was identified single crystal X-ray crystallography. Four protopine protoberberine isoquinoline (protopine, scoulerine, cheilanthifoline, stylopine) along one gerdae. plant. MS ¹H-NMR comparison. The testing crude methanol extracts, (atisinium orochrine protopine) plants found inactive against bacterium Staphylococcus aureus (MIC = >125 μg/ml) Vancomycin resistant Enterococcus faecium μg/ml). But vitro assay protopine, cheilanthifoline gave very significant activity Plasmodium falciparum, TM4 K1 strains. Crude extract (AO-ME) not active (IC₅₀ >10 μg/ml both strains). Increased observed its (AOCEA) IC₅₀ values 20.40 19.20 further increased 4.02 μM TM4/8.2 3.59 K1CB1 strains. The better extracts Its (CG-ME) 1.00 strain 2.56 strain. far 0.33 0.63 Protopine 4.25 4.29 Cheilanthifoline 3.76 2.78 strains. These become candidates leads. Similar activities may be expected ones plants. Therefore, combination would make best herbal mixture Bhutanese medicines. results proved ethno-directed biorational approach, combined focus, efficient strategy lead discovery. first time at level clinical efficacy. Bhutan thus provide important Bioprospecting them benefit local people, industries patients large.