Biomedical subjects
Publications and source records attributed to Feng-Peng Wang.
Two new C19-diterpenoid alkaloids, circinadines A (1) and B (2), were isolated from the roots of Aconitum hemsleyanium var. circinacum. Their structures were elucidated by chemical evidence and spectral analyses, including ESI-MS, HR-EI-MS, 1D- and 2D-NMR.
Two new C(19)-diterpenoid alkaloids, piepunensine A (1) and 18-acetylcammaconine (2), have been isolated from the roots of Aconitum piepunense together with five known alkaloids pengshenine B (3), talatisamine (4), aconosine (5), yunaconitine (6), and talatizidine (7). The structures of the new alkaloids were established on the basis of spectral data (1D- and 2D-NMR, HR-MS).
Three new C20-diterpenoid alkaloids, trifoliolasines D-F (1-3), were isolated from the aerial parts of Delphinium trifoliolatum, and their structures were determined by the interpretation of spectroscopic data and by the single-crystal X-ray crystallographic analysis of 1.
We examined the ability of partially synthesized new compounds from fangchinoline and tetrandrine to reverse P-glycoprotein (P-gp)-dependent multidrug resistance (MDR) in vitro and in vivo. All compound enhanced the in vitro cyctotoxic effect of vinblastin (VBL) at 0.1 microM as potent as 10 microM verapamil against the resistant cell line P388/ADR. The combination effect tended to be strong by substitution of bulky group, resulting 5,14-dibromotetrandrine (compound #9) showed the strongest effect. Compound #9 increased intracellular VBL accumulation in P388/ADR cells, much stronger than verapamil, as well as cytotoxic combined effect. This mechanism seems to inhibit the function of P-gp, but not the expression of P-gp. In combination with VBL, this compound also synergistically prolonged the life-span of P388/ADR-bearing mice. Bisbenzylisoquinoline alkaloids and their derivatives are possible to be good candidates as modifier of MDR in cancer chemotherapy.
Treatment of a lycoctonine-type alkaloid acetyllycoctonine (4) with mCPBA at room temperature led to acetyllycoctonine N-oxide (5) as the major product together with other interesting compounds 6-12 as the minor products, which were derived from oxidation involving the nitrogen atom and Cope elimination as well as Polonovski-like fragmentation. All of those new compounds (5-12) were fully characterized.
PURPOSE: The present study aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet), a bromized derivative of tetrandrine (Tet), in vitro and in vivo. METHODS: Drug sensitivity was determined using the MTT assay. The in vivo effect of Tet was investigated using nude mice grafted with sensitive and resistant KB human epidermoid cancer cells. Doxorubicin (Dox) accumulation was analyzed by fluorospectrophotometry and the protein and mRNA levels of P-glycoprotein (P-gp) were determined by immunocytochemistry and RT-PCR, respectively. RESULTS: BrTet at 0.25, 0.5 and 1 micro M reversed Dox resistance in MDR human breast cancer MCF-7/Dox cells dose-dependently and its potency was greater than that of Tet at the same concentrations. BrTet reversed vincristine (VCR), Dox and paclitaxel resistance in MDR human oral epidermoid carcinoma KBv200 cells as well as innate VCR and Dox resistance in human hepatocellular carcinoma Bel(7402) cells. However, BrTet showed no effect on the IC(50) values of the above-mentioned anticancer drugs in sensitive MCF-7 and KB cells. No reversal effect of BrTet on the cytotoxicity of 5-fluorouracil and cisplatin, non-P-gp substrates, was observed. In nude mice bearing KBv200 xenografts on the left flank and KB xenografts on the right flank, i.p. injection of 5 mg/kg and 10 mg/kg BrTet significantly enhanced the antitumor activity of Dox against KBv200 xenografts with inhibitory rates of 33.0% and 39.2%, while Dox alone inhibited the growth of KBv200 xenografts by only 11.6%. No enhancement by BrTet was seen in KB xenografts. Moreover, BrTet at 5 mg/kg reversed paclitaxel resistance in KBv200 xenografts. Fluorospectrophotometric assay showed that BrTet significantly increased the intracellular accumulation of Dox in MCF-7/Dox cells in a dose-dependent manner. BrTet also inhibited the overexpression of P-gp in MCF-7/Dox cells, but had no effect on mdr1 expression. CONCLUSIONS: BrTet showed significant MDR reversal activity in vitro and in vivo. Its activity may be related to the inhibition of P-gp overexpression and the increase in intracellular accumulation of anticancer drugs. BrTet may be a promising MDR modulator for eventual assessment in the clinic.
Three new cyclic octapeptides, microtoenins A-C (1-3), and a new glycoside, 3'''-O-methylcrenatoside (4), along with several known compounds, were isolated from the ethanolic extract of the stems of Microtoena prainiana. Their structures were determined by spectral and chemical evidence. At a concentration of 0.01 mg/mL, 3'''-O-methylcrenatoside (4), crenatoside (5), and isocrenatoside (6) inhibited angiotensin converting enzyme (ACE) activity by more than 30%.
Two new C19-diterpenoid alkaloids, kongboentine A (1) and kongboentine B (3), were isolated from the roots of Aconitum kongboense Lauener and their structures were elucidated by spectral data.
Six new artificial products 11-16 were obtained from the reaction of acetyllycoctonine (10) with N-bromosuccinimide (NBS). The structures of these compounds were established on the basis of spectral data. It is emphasized that the varieties and yields of the products in this reaction depended greatly upon reaction conditions and the types of substrate.
Three new norditerpenoid alkaloids, trifoliolasines A (1), B (3), and C (5), were isolated from the whole plant of Delphinium trifoliolatum FINET et GAGNEP, and their structures were established based on the spectral data.
Further investigation of the roots of Delphinium giraldii DIELS led to the isolation of three new C(19)-diterpenoid alkaloids, giraldines G (1), H (2), and I (3). The structures of 1-3 were established based on spectroscopic evidence.
Four new norditerpenoid alkaloids, leueantines A (1), B (2), C (3), and D (4), were isolated from the roots of Aconitum hemsleyanum var. leueanthus. The structures of 1-4 were established by spectroscopic evidence.
Following the report on the synthesis of the 7,17-seco compounds [Wang, F.P., Yang, J.S., Chen, Q.H., Yu, L. and Li, B.G. (2000), Chem. Pharm. Bull. 48, 1912-1916], further studies on the reaction optimization for cleavage of the C(7),C(17) bond led to the 7,17-seco norditerpenoid alkaloids (e.g. 4, 9) in nearly 90% yield.
A new franchetine-type (leueandine 1) and two new lycoctonine-type [potanisines F (3) and G (5)] C19-diterpenoid alkaloids have been isolated from the roots of Aconitum hemsleyanum var. leueanthus and Delphinium potaninii, respectively, and their structures were established on the basis of spectral data.
The new compound hemsleyatine (1) was isolated along with four known C(19)-diterpenoid alkaloids: indaconitine (4), yunaconitine (5), chasmanine (6), and talatisamine (7) from the roots of Aconitum hemsleyanum PRITZ. Structures were established by spectral analysis, including tow dimeusional (2D) NMR spectroscopy and a chemical method. Hemsleyatine (1) is the first C(19)-diterpenoid alkaloid bearing the 8-amino group. In addition, the assignments of some (13)C signals for pseudaconine (3) were revised by comparison with those of hemsleyatine (1).
From the roots of Delphinium potaninii var. jiufengshanense, two new lycoctonine-type C(19)-diterpenoid alkaloids called jiufengdine (1) and jiufengtine (4) have been isolated. The structures of the new alkaloids (1, 4) were established by 1D and 2D NMR spectra.
After a series of optimization for the reaction conditions (reagents, reaction temperature, etc.), treatment of the sulfonates 4, 8, 13 and 15 with 8% NaOH (room temperature, 24 h) via a semipinacol rearrangement afforded the corresponding C-nor compounds 5, 9, 12 and 16, as the major of a pair of epimer at C-16, to an excellent extent, in 95%, 92%, 100% and 90% yield, respectively. The 12,13-seco compounds 21 and 22 (23) were obtained in 20% and 60% yield, respectively, by treating 5 with Br(2)-glacial HOAc (room temperature, 24 h). Treatment of the C-nor compounds 5 or 6, 16 or 17, and 28 from 10 with SOCl(2)-anhydrous benzene (room temperature, overnight) afforded the 12,13-seco compounds 24, 26 and 30 in 70% or 100%, 40% and 66% yield, respectively. When treatment of the C-nor compound 29 from 9 under same conditions gave the 12,13-seco products 30, 31 and 32 in 33%, 26% and 20% yield. When treating 21 or 24, and 26 with 5% KOH in EtOH afforded the 12,13-seco compounds 25 and 27 quantitatively, respectively. The compound 31 converted to 30 quantitatively by treatment with Na(2)CO(3) in MeOH. All of the new compounds were isolated and fully characterized.