Chemical components of Aconitum barbatum var. puberulum and their cytotoxic and antibacterial activities.

Nineteen compounds, including seventeen alkaloids O-methylarmepavine (1), (S)-6-methoxy-1-(4-methoxybenzyl)-2-methyl -1,2,3,4-tetrahydroisoquinolin-7-ol (2), (+)-(IR,laR)-lahydroxymagnocurarin (3), (6R,6aS,P)-(+)-corydine (4), (+)-N-methyllaurotetanine (5), magnoflorine (6), 3-hydroxy-1,2-dimethoxy-5-methyl-5H-dibenzoindol-4-one (7), imperialine (8), crispine B (9), (S)-1-(3-methoxyphenyl)-N-methylpropan-2-amine (10), methyl 2- (acetamino)benzoate (11), 2-carboxyoxanilic acid methylester (12), 4-[2-(methoxycarbonyl) anilino]-4-oxobutanoic acid methyl ester (13), N-methylcorydaldine (14), N-methyl-6,7- dimethoxyisoquinolone (15), (5S,6R,7S,8R)-5-amino-(2Z,4Z)-1,2,3-trihybuta-2,4-dienyloxypentane- 6,7,8,9-tetraol (16), nicotinic acid (17), and two megastigmane type compounds, S(+)- dehydrovomifoliol (18) and megastigmane (19), were isolated from the Aconitum barbatum var. puberulum Ledeb. Compounds 1-3 and 5-19 were isolated from this plant for the first time, of which compound 11 was isolated from natural source for the first time. Cytotoxicity evaluation revealed that compound 5 displayed mild cytotoxicity against the Hela cell lines (IC50 13.69 ± 0.036 µM). Antibacterial activity evaluation revealed that compounds 1 and 6 showed strong antibacterial activity against the Gram-positive bacterium, S. aureus.

Diterpenoid alkaloids from Aconitum barbatum var. puberulum Ledeb.

Seven previously undescribed diterpenoid alkaloids, including five C20-diterpenoid alkaloids, barpuberudine, barpubesines A-D, and two C18-diterpenoid alkaloids, barpubenines A-B, along with 11 known diterpenoid alkaloids were isolated from the whole plant of Aconitum barbatum var. puberulum Ledeb. (Ranunculaceae). Barpuberudine is an unprecedented carbon skeleton of C20-diterpenoid alkaloid, while barpubenines A-B are the first example of rearranged types in C18-diterpenoid alkaloids. Their structures were elucidated based on a comprehensive spectroscopic data analysis. The probable pathway of biogenesis of barpuberudine and barpubenines A-B were discussed. Additionally, the antiarrhythmic, cytotoxic and antimicrobial activities of isolates were also evaluated.

Optimal timing of bisphosphonate administration in combination with samarium-153 oxabifore in the treatment of painful metastatic bone disease.

While bisphosphonates are indicated for prevention of skeletal-related events, radionuclide therapy is widely used for treatment of painful bone metastases. Combined radionuclide therapy with bisphosphonates has demonstrated improved effectiveness in achieving bone pain palliation in comparison to mono therapy with radionuclides or bisphosphonates alone. However, there are conflicting reports as to whether bisphosphonates adversely influence skeletal uptake of the bone-seeking radiotracers used for therapy. Recent studies analyzing influence of Zoledronic acid on total bone uptake of Samarium-153 EDTMP (Sm-153 EDTMP) by measuring cumulative urinary activity of Sm-153 on baseline study, as well as in combination with bisphosphonates (administrated 48 hours prior to Sm-153) did not provide any statistically significant difference in urinary excretion of Sm-153 between the two groups. It may be noted that the exact temporal sequence of bisphosphonate administration vis a vis radionuclide therapy has not yet been studied. One of the side effects of bisphosphonates is transient flare effect on bone pain. Radionuclide therapy may also have similar side effect. Keeping in view the above the current study was designed with the main objective of determining the exact timing of bisphosphonate administration in patients receiving combined therapy so as to achieve optimal efficacy of bone pain palliation. Ninety-three patients suffering from metastatic bone pain who received combination therapy with Sm-153 oxabifore (an analog of Sm-153 EDTMP) and Zoledronic acid were divided into three groups according to the timing of Zoledronic acid administration: Group I: 39 patients who received Zoledronic acid 7 or more days prior to Sm-153 oxabifore treatment; Group II: 32 patients who received Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment and Group III: 22 patients who received Zoledronic acid 7 days after Sm-153 oxabifore treatment. Sm-153 oxabifore was administered to all patients at the standard bone palliation dose of 37 MBq/kg body weight. All patients received Zoledronic acid before and after treatment in standard dosage of 4 mg every 28 days. WB bone scan, CT, and MRI were performed before treatment in all patients to exclude cord compression and vertebral fractures. Pain scores and quality of life (QOL) measurements were recorded meticulously in all patients. In groups I, II, and III, pain relief occurred in 10.4 ± 3.1 (Range = 5-15); 3.1 ± 1.1 (Range = 1-5) and 22 ± 5.1 (Range = 15-35) days, respectively, following radionuclide therapy. There was statistically significant difference between pain score in all groups before and after treatment as well as statistically significant difference in time to pain relief onset between Group II and other groups of patients (P < 0.0001). Based on our results we concluded that administration of Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment helps in achieving better pain relief, as well as at the shortest time interval from the start of therapy.