A new sesquiterpene lactone from Elephantopus tomentosus

A new sesquiterpene lactone, named tomenphantopin H (1), together with two known germacranolides, 2β-methoxy-2-deethoxy-8-O-deacylphantomolin-8-O-tiglinate (2) and 2-deethoxy-2-hydroxyphantomolin (3), was isolated from the whole plant of Elephantopus tomentosus Linn. The new compound was completely elucidated using a combination of 1D and 2D NMR techniques (COSY, HMQC, and HMBC) and HR-ESI-MS analyses. All compounds exhibited antibacterial activity.     

A new elemanolide sesquiterpene lactone from Elephantopus scaber

A new elemanolide sesquiterpene lactone, named elescaberin (1), together with two known compounds, namely, isodeoxyelephantopin (2) and deoxyelephantopin (3), was isolated from the whole plant of Elephantopus scaber. The structure of 1 was elucidated on the basis of spectroscopic analysis. All three compounds exhibited significant inhibitory activities against human SMMC-7721 liver cancer cells in vitro (IC₅₀ 8.18–14.08 μmol/l).     

Argutalactone,an unprecedented sesquiterpenoid lactone with a 6/5/7 tricyclic system from Incarvillea arguta

Argutalactone (1), a novel sesquiterpenoid lactone featuring an unprecedented 6/5/7 rigid skeleton, was isolated from the roots of Incarvillea arguta. The structure and relative configuration of 1 were established by extensive analysis of spectroscopic data. The absolute configuration of 1 was determined as 2R,5S,10R,12S based on the analysis of biogenetical transformation, comparison of the optical rotation with literature data, and comparison of the experimental circular dichroism spectrum with the calculated electronic circular dichroism spectra.     

Excretion Into Gastrointestinal Tract of Irinotecan Lactone and Carboxylate Forms and Their Pharmacodynamics in Rodents

Purpose. To investigate the excretion of irinotecan hydrochloride (CPT-11) and its active metabolite, SN-38, into the gastrointestinal lumen via the biliary and/or intestinal membrane route after dosing with lactone and carboxylate forms of CPT-11, and to evaluate the toxic and antitumor effects of the two forms. Methods. The excretions of CPT-11 and SN-38 were investigated by the in situ perfusion technique using rats. The incidence of delayed diarrhea was evaluated after i.v. dosing (60 mg/kg) with CPT-11 lactone and carboxylate forms for 4 days. Antitumor activity and changes in body weight were investigated in mice with Meth A tumors. Results. The excretion of CPT-11 into bile was greater in dosing with CPT-11 carboxylate than that with its lactone form, whereas the exsorption across intestinal membrane was greater in dosing with CPT-11 lactone than that with its carboxylate form. Dosing with CPT-11 lactone dose-dependently inhibited the increase in tumor weights in Meth A tumor mice, whereas the dosing with its carboxylate form reduced the antitumor effect. Conclusions. The decreased antitumor effect caused by dosing with the CPT-11 carboxylate form could be due to less accumulation in the tissue including tumor cells resulting from the rapid elimination of the form in the body.     

A new sesquiterpene lactone glycoside and a new quinic acid methyl ester from Patrinia villosa

A new sesquiterpene lactone glycoside (1) and a new quinic acid methyl ester (2) were isolated from Patrinia villosa, together with another two known compounds chlorogenic acid n-butyl ester (3), 3, 4-di-O-caffeoylquinic acid methyl ester (4). Their structures were established using 1D/2D-NMR spectroscopy, mass spectrometry, and comparing with spectroscopic data reported in the literature.     

Triterpenoids from the barks of Terminalia chebula

Two new triterpenoids, termichebuloside A (1), an unusual dimeric triterpenoid saponin, and termichebulolide (2), an oleanolic acid-type lactone, along with 11 known triterpenoids, were isolated from MeOH extract of the barks of Terminalia chebula. The structures of 1 and 2 were elucidated to be arjunglucoside I-(3-O-19′,23-O-19′)-18,19-seco-19-hydroxyarjunglucoside I (1) and 2α,3β,23-trihydroxyolean-11,13(18)-dien-28,19β-olide (2), respectively, on the basis of spectroscopic evidences and biogenetic consideration.     

依达拉奉联合银杏二萜内酯葡胺注射液治疗急性脑梗死的临床疗效观察

目的 研究依达拉奉联合银杏二萜内酯葡胺注射液治疗急性脑梗死（ACI）的临床疗效,探讨治疗ACI更为有效的治疗方案。方法 收集2014年1月至2015年1月于解放军463医院神经内科住院治疗的ACI患者100例,根据随机数字表法将患者分为观察组和对照组,每组各50例,观察组在常规治疗基础上加用依达拉奉和银杏二萜内酯葡胺注射液,对照组在常规治疗基础上加用银杏二萜内酯葡胺注射液。两组均连续治疗14 d,于治疗前、后采用神经功能评分比较,观察两组患者的临床疗效、不良反应和治疗满意度,并进行统计分析。结果 治疗前两组的神经功能缺损（NIHSS）评分无显著差异（P>0.05）。治疗后观察组的NIHSS评分明显优于对照组（P<0.05）。观察组总有效率为90%,对照组为66%,差异有统计学意义（P<0.05）。两组发生的主要不良反应有皮疹、恶心、头晕,且不良反应发生率无明显差异（P>0.05）。观察组患者的治疗满意度为94%,对照组为84%,差异有统计学意义（P<0.05）。结论 在ACI常规治疗基础上,加用依达拉奉和银杏二萜内酯葡胺注射液,能够显著改善ACI患者的神经功能,提高治疗满意度,值得在临床推广使用。     

Stability and Release Performance of a Series of Pegylated Copolymeric Micelles

Purpose. The aim of this work is to evaluate the capability of a series of biocompatible amphiphilic copolymers as a nano-sized drug carrier. Methods. The influences of the type of lactone monomer, the feed molar ratios of lactone/PEG, and the molecular weight of PEG on the performance and release behavior of micelles are investigated. Results. These pegylated amphiphilic copolymers efficiently form micelles with a low CMC value in the range of 10^–6-10^–7 M. The average particle size of micelles is 100 nm. The phenomenon of increasing particle size as increasing the chain length of poly(lactone) block is observed. The different hydrophobicity, based on chemical structure of poly(lactone), accounts for different interaction strength between indomethacin and hydrophobic inner core, which further influences the drug loading in copolymeric micelles and their release character. In addition, the PCL/PEG/PCL micellar solutions maintain their sizes at 4°C for 8 weeks without occurring significant aggregation or dissociation. Conclusions. A series of biocompatible pegylated amphiphilic copolymers have been elucidated possessing micellization potential to form nano-sized micelles in an aqueous environment, which enable incorporate hydrophobic drug and regulate drug release.     

路路通内酯的化学结构

用红外,质谱,¹H,¹³CNMR和¹H-¹³CCOLOC等光谱解析,确定了新化合物路路通内酯的结构为3-羰基-11α,12α-环氧-13β-氧-齐墩果-28β-酸-13,28-γ-内酯,命名为路路通内酯。     

Two new sesquiterpene lactone glycosides from Artemisia frigida Willd.

The investigation of EtOAc-soluble fraction from the aerial parts of Artemisia frigida has led to the isolation of two new sesquiterpene lactone glycosides, named as artemofriginoside A and artemofriginoside B. Their structures were characterized as 3β-(β-d-glucopyranosyloxy)-8β-(p-hydroxyphenylacetyloxy)-4(15),10(14),11(13)-guaiatrien-1α,5β,6β,7αH-12,6-olide (1) and β-(β-d-glucopyranosyloxy)-8β-(2-hydroxy-3-methylbutanoyloxy)-4(15),10(14),11(13)-guaiatrien-1α,5β,6β,7αH-12,6-olide (2), on the basis of 1D and 2D NMR spectral analysis.     

Stable Supersaturated Aqueous Solutions of Silatecan 7-t-Butyldimethylsilyl-10-Hydroxycamptothecin via Chemical Conversion in the Presence of a Chemically Modified β-Cyclodextrin

Purpose. A method for obtaining clear supersaturated aqueous solutions for parenteral administration of the poorly soluble experimental anti-cancer drug silatecan 7-t-butyldimethylsilyl-10-hydroxycamptothecin (DB-67) has been developed. Methods. Equilibrium solubilities of DB-67 were determined in various solvents and pH values, and in the presence of chemically modified water-soluble -cyclodextrins. The stoichiometry and binding constants for complexes of the lactone form of DB-67 and its ring-opened carboxylate with sulfobutyl ether and 2-hydroxypropyl substituted -cyclodextrins (SBE-CD and HP-CD) were obtained by solubility and circular dichroism spectroscopy, respectively. Kinetics for the reversible ring-opening of DB-67 in aqueous solution and for lactone precipitation were determined by HPLC with UV detection. Results. Solubilities of DB-67 lactone in various injectable solvent systems were found to be at least one order of magnitude below the target concentration (2 mg/ml). DB-67 forms inclusion complexes with SBE-CD and HP-CD but the solubilization attainable is substantially less than the target concentration. Slow addition of DB-67/DMSO into 22.2% (w/v) SBE-CD failed to yield stable supersaturated solutions due to precipitation. Stable supersatured solutions were obtained, however, by mixing a concentrated alkaline aqueous solution of DB-67 carboxylate with an acidified 22.2% (w/v) SBE-CD solution. Ring-closure yielded supersaturated solutions that could be lyophilized and reconstituted to clear, stable, supersaturated solutions. Conclusions. The method developed provides an alternative to colloidal dispersions (e.g., liposomal suspensions, emulsions, etc.) for parenteral administration of lipophilic camptothecin analogs.     

Synthesis of an actinomycin-related peptide lactone from the corresponding cyclic pentapeptide by NO-acyl shift

The N,O-acyl shift was investigated as a method for the synthesis of an O-peptide or peptide lactone from a linear or cyclic peptide respectively. Protected derivatives of glycyl-l -threonine could be converted to O-peptides by the action of HCl/dioxane at room temperature and N-acylated under conditions which precluded a reverse O,N-acyl shift. For effecting N,O-acyl shift in cyclo(Thr-d -Val-Pro-Sar-MeAla) this reagent was unsatisfactory and p-toluenesulfonic acid in dioxane at 80° was used instead. The resulting crystalline peptide lactone p-toluenesulfonate salt was N-acylated with 3-benzyloxy-4-methyl-2-nitroben-zoyl chloride to afford a known intermediate in the synthesis of 5,5′-MeAla actinomycin D. This approach constitutes a novel synthetic route to actinomycins and potentially to other peptide lactone antibiotics.     

Slow O,N-acyl shift in an actinomycin-related peptide lactone

The pentapeptide lactone Cbz-(Thr-D-Val-Pro-Sar-MeAla-) was synthesized in order to observe the behavior of the unprotected lactone resulting from its hydrogenolytic deprotection. Closely related peptide lactones have been reported as intermediates in total syntheses of actinomycin D and its analogues, despite the fact that unprotected and unprotonated O-peptides of serine and threonine are known to undergo rapid O,N-acyl shift. In the present study the peptide lactone was seen to undergo a slow O,N-acyl shift, in a matter of hours, to the known cyclic pentapeptide. This contrasted with the rapid rearrangement of a model O-peptide, O-hippuryl-L-threonine methyl ester. This slowness of an O,N-acyl shift in a cyclic system presumably results from higher energy barriers of conformational origin. It explains the suitability of unprotected peptide lactones for the syntheses of actinomycins and other peptide lactone antibiotics which have appeared in the literature.     

New cytotoxic sesquiterpene lactones from Anthemis scrobicularis

Four new sesquiterpene lactones, 4α-hydroxy-guaia-10(14),11(13)-diene-12,6α-olide (1), 4α-hydroxy-9α-acetoxy-guaia-1(10),2-diene-12,6α-olide (4), 4α-hydroxy-9β-acetoxy-guaia-1(10),2-diene-12,6α-olide (5), and 1α,4α-dihydroxy-9α-acetoxy-guaia-10(14),2-diene-12,6α-olide (6), were isolated from the aerial parts of Anthemis scrobicularis. Their structures were elucidated on the basis of their IR, NMR, and MS spectroscopic data. In addition, two known sesquiterpene lactones micheliolide (2) and achillin (3) were also isolated. The cytotoxicity of some of the isolated compounds was tested against HCT 116, HepG-2, and MCF-7 cell lines. Micheliolide and 4α-hydroxy-guaia-10(14),11(13)-diene-12,6α-olide showed pronounced inhibitory activity while 4α-hydroxy-9α-acetoxy-guaia-1(10),2-diene-12,6α-olide showed weak activity.     

A New Sesquiterpene Lactone Glucoside from Ixeris Sonchifolia

Abstract

A new sesquiterpene lactone glucoside, Ixerin Z₁ (1), was isolated from the whole plants of Ixeris sonchifolia (Bge.) Hance, along with 15 known compounds. The structure of 1 was elucidated as 1(10),3,11(13)-guaiatriene-12,6-olide-2- one-3-O-[6′-(p-hydroxyphenylaceryl)]-gluco-pyranoside by spectroscopic methods including 2D-NMR techniques.     

Two new guaiane sesquiterpene lactones from the aerial parts of Artemisia vulgaris

Abstract

Two new guaiane sesquiterpene lactones, vulgarolides A and B (1 and 2), were isolated from Artemisia vulgaris aerial parts using various chromatographic separations. The structure elucidation was performed by combination of spectroscopic experiments including 1D and 2D NMR, HR ESI MS, and CD. Their in vitro cytotoxic activities against five human cancer cell lines were also evaluated using SRB method.     

A new lindenane-type sesquiterpenoid lactone from Chloranthus japonicus

Chromatographic fractionation of the EtOH extracts of the Traditional Chinese Medicine (TCM) Chloranthus japonicus, has led to the isolation of a new lindenane-type sesquiterpenoid lactone derivative (1). Rosmarylchloranthalactone E (1), which consists of lindenane sesquiterpenoid lactone and rosmarinic acid moieties linked via an ester bridge, was structurally elucidated by 1D and 2D NMR and HRMS data. Compound 1 was a potent phosphodiesterase-4 (PDE4) inhibitor with an IC₅₀ value of 0.96 ± 0.04 μM.     

Effect of P-Glycoprotein Modulator,Cyclosporin A,on the Gastrointestinal Excretion of Irinotecan and Its Metabolite SN-38 in Rats

Purpose. The purpose of this work was to investigate the role of the hepatic and intestinal P-glycoprotein (P-gp) and canalicular multispecific organic anion transporter /multidrug resistance-associated protein 2 (cMOAT/MRP2) on both biliary excretion and intestinal exsorption of irinotecan hydrochloride (CPT-11) and its metabolite, SN-38, in the lactone and carboxylate forms. Cyclosporin A (CsA) was used to modulate P-gp and cMOAT/MRP2. Methods. The transcellular transport of CPT-11 and SN-38 was examined by using LLC-PK1 derivative cell lines transfected with murine mdr1a both in the absence or in the presence of CsA. The excretions of the compounds through the biliary and intestinal membrane routes were investigated by in situ perfusion technique. Results. Basolateral-to-apical transport of CPT-11 lactone in L-mdr1a cells was significantly decreased by CsA (10 M). The trans- cellular transport of SN-38 lactone showed similar behaviors as those of CPT-11 lactone. The biliary excretion and the intestinal exsorption of both forms of CPT-11 and SN-38 were significantly inhibited when the drug was co-administered with CsA. Conclusions. The transports of CPT-11 and SN-38 via the biliary route seem to be essentially related with cMOAT/MRP2, whereas those of both compounds via the intestinal membrane seem to be related with P-gp.     

正交试验法优选胃乐舒颗粒的醇提工艺

目的：优选胃乐舒颗粒药材中醇溶性成分的提取工艺.方法：以延胡索乙素、木香烃内酯、去氢木香内酯提取量和浸膏收率为评价指标,采用正交试验设计确定最佳醇提工艺.结果：胃乐舒颗粒最佳提取工艺为：加6倍量的80%乙醇,加热回流3次,每次1 h.结论：该提取工艺高效、稳定,适用于大生产.     

Three Lupane Derivatives from Leptospermum scoparium

The ether extract of the aerial parts of Leptospermum scoparium cultivars yielded a lactone with a 20,29,30- trinorlupane skeleton ( 1 ). Furthermore, 2α-hydroxyursolic acid ( 2 ), platanic acid ( 3 ) and 3β,30-dihydroxy-lup-20(29)-en-28-oic acid ( 4 ) were isolated.