Tripfordines A-C, sesquiterpene pyridine alkaloids from Tripterygium wilfordii, and structure anti-HIV activity relationships of Tripterygium alkaloids

Three new sesquiterpene pyridine alkaloids, tripfordines A-C (1-3), were isolated from an ethanolic extract of the roots of Tripterygium wilfordii, along with eight known pyridine alkaloids, and tested for in vitro cytotoxic and anti-HIV activity. The structures of the new compounds were established on the basis of spectroscopic data interpretation. Anti-HIV structure-activity relationships (SAR) for this compound type are proposed on the basis of the screening results from the newly isolated compounds and prior data of known sesquiterpene pyridine alkaloids. The position of a carboxyalkyl chain on the pyridine moiety was not critical since both 2'- and 4'-substituted compounds exhibited high anti-HIV activity (EC(50) 0.1 microg/mL). In contrast, a hydroxy group at C-8' (carboxypropyl side chain) or C-9' (carboxybutyl side chain) was found to affect anti-HIV activity.     

Rotundines A-C, three novel sesquiterpene alkaloids from Cyperus rotundus

Rotundines A (1), B (2), and C (3), three novel sesquiterpene alkaloids with an unprecedented carbon skeleton, were isolated from the rhizomes of Cyperus rotundus. The structures of 1-3 were elucidated by spectral and chemical methods.     

Cytotoxic constituents of the fruits of Cananga odorata

A new guaipyridine sesquiterpene alkaloid, cananodine (1), and two new eudesmane sesquiterpenes, cryptomeridiol 11-alpha-L-rhamnoside (2) and gamma-eudesmol 11-alpha-L-rhamnoside (3), along with gamma-eudesmol (4), were isolated from the fruits of Cananga odorata. The structures of compounds 1-3 were established on the basis of NMR and MS methods. In addition, compounds 1-4 and four previously reported alkaloids, cleistopholine (5), N-trans-feruloyltyramine (6), (+)-ushinsunine-beta-N-oxide (7), and lyscamine (8), were evaluated for cytotoxicity against two human hepatocarcinoma cell lines.     

Immunosuppressive sesquiterpene alkaloids from Tripterygium wilfordii

Nine new sesquiterpene pyridine alkaloids [wilfornines A (1), B (2), C (3), D (4), E (5), F (8), and G (9); wilfordinines I (6) and J (7)] and six known compounds (10-15) were isolated from a clinically used extract (T(II)) of Tripterygium wilfordii. The structures of 1-9 were elucidated by spectroscopic and chemical methods. The inhibitory effects on cytokine production of 1-3 and several related compounds were evaluated. Compounds 10 and 14 showed significant inhibitory effects on cytokine production.     

Oppositines A and B, sesquiterpene pyridine alkaloids from a Sri Lankan Pleurostylia opposita

Two new sesquiterpene pyridine alkaloids, oppositines A (1) and B (2), have been isolated from the plant Pleurostylia opposita, collected in Sri Lanka. The compounds were isolated and purified by solvent/solvent partitioning, column chromatography, and HPLC. Their structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Oppositines A (1) and B (2) showed moderate cytotoxicity against HCT116 cell lines with EC50 values of 27 +/- 2 and 26 +/- 3 microM, respectively.     

Sesquiterpene alkaloids from Tripterygium hypoglaucum and Tripterygium wilfordii: a new class of potent anti-HIV agents

Five new sesquiterpene pyridine alkaloids [triptonines A (1) and B (2), and wilfordinines A (3), B (4), and C (5)] and two known compounds (peritassine A and hypoglaunine C) were isolated from Tripterygium hypoglaucum and a clinically used extract of Tripterygium wilfordii. The structures of 1-5 were elucidated by spectroscopic methods. The anti-HIV activity of 1, 2, and several related compounds was evaluated. Triptonine B (2) demonstrated potent anti-HIV activity with an EC(50) value of <0.10 microg/mL and an in vitro therapeutic index value of >1000.     

Dihydroagarofuran sesquiterpene alkaloids from Maytenus putterlickoides

Two new dihydroagarofuran sesquiterpene alkaloids, putterines A (2) and B (3), and a known alkaloid, mayteine (1), were isolated from the root of Maytenus putterlickoides. The structures of these compounds were elucidated by various spectroscopic techniques, including 1H and 13C NMR, COSY, ROESY, HMBC, and high-resolution FABMS.     

Antiprotozoal sesquiterpene pyridine alkaloids from Maytenus ilicifolia

As part of a bioprospecting program aimed at the discovery of antiprotozoal agents from the Brazilian flora, two new sesquiterpene pyridine alkaloids, ilicifoliunines A (1) and B (2), along with the known alkaloids aquifoliunine E-I (3) and mayteine (4), were isolated from the root bark of Maytenus ilicifolia. The structures of 1 and 2 were established on the basis of spectroscopic data interpretation. Alkaloid 3 displayed potent in vitro antiprotozoal activity against Leishmania chagasi and Trypanosoma cruzi, with IC(50) values of 1.4 and 41.9 μM, respectively, as well as low cytotoxicity against murine peritoneal macrophages (IC(50) of 1.8 mM).     

雷公藤中倍半萜生物碱类化学成分的研究

目的 对雷公藤Tripterygium wilfordii乙醇提取物氯仿部位中的倍半萜生物碱类成分进行研究。方法 采用酸提碱沉法,结合中性氧化铝、十八烷基硅烷键合硅胶（ODS）及半制备高效液相等多种色谱技术进行分离纯化,并运用1D-NMR、2D-NMR、MS、ECD等波谱学方法对化合物进行结构鉴定。结果 从雷公藤乙醇提取物氯仿部位中分离得到5个倍半萜生物碱类成分,分别鉴定为(1S,4S,5R,6R,7R,8S,9S,10S)-1,8,11-triacetoxy-7-nicotinoyloxy-4,5-dihydroxy-dihydroagarofuran(1）、triptersinine U(2）、macroregeline F(3）、雷公藤宁碱B(4）和triptonine B(5）。结论 化合物1为新化合物,命名为雷公藤司宁Z15;化合物3为首次从该植物中分离得到。     

Farnesylamine from the ant Monomorium fieldi Forel

(2E)- and (2Z)-Farnesylamine were detected in the extracts of the myrmicine ant Monomorium fieldi Forel from Australia. Their structures were established by direct comparison with synthetic (2E)- and (2Z)-farnesylamine. This finding of a sesquiterpene is unique in a genus known to produce unbranched fatty acid derived alkaloids and amines. Additionally, while farnesylamine has not been reported from natural sources, the synthetic material has been shown to have a variety of biological activities.     

Insecticidal sesquiterpene pyridine alkaloids from Maytenus chiapensis

The new sesquiterpene pyridine alkaloids chiapenines ES-I (1), ES-II (2), ES-III (3), and ES-IV (4), in addition to the known alkaloids wilfordine (5), alatamine (6), wilforidine (7), alatusinine (8), euonine (9), euonymine (10), ebenifoline E-I (11), forrestine (12), mayteine (13), and 4-hydroxy-7-epi-chuchuhuanine E-V (14), were isolated from the leaves of Maytenus chiapensis. Their structures were elucidated by 1D and 2D NMR spectroscopy, including homonuclear and heteronuclear correlation (COSY, ROESY, HSQC, and HMBC) experiments. Wilfordine, alatusinine, and euonine exhibited strong antifeedant activity against Spodoptera littoralis.     

Lindenane sesquiterpene dimers from Chloranthus fortunei

Five new lindenane sesquiterpene dimers ( 1- 5), named shizukaols K-O, and eight known sesquiterpene dimers were isolated from the roots of Chloranthus fortunei. The structures of 1- 5 were elucidated using spectroscopic data, mainly 1D NMR, 2D NMR, and mass spectra.     

Dihydrobenzo[c]phenanthridine alkaloids from stem bark of Zanthoxylum nitidum

Five novel alkaloids, zanthomuurolanine ( 1), epi-zanthomuurolanine ( 2), zanthocadinanines A ( 3) and B ( 4), and epi-zanthocadinanine B ( 5), composed of dihydrochelerythrine and a cadinane-type sesquiterpene linked by a methylene bridge, have been isolated from stem bark of Zanthoxylum nitidum. These structures were elucidated by spectroscopic techniques (UV, IR, MS, CD, 1H NMR, 13C NMR, DEPT, COSY, NOESY, HSQC, and HMBC analyses). Single-crystal X-ray diffraction studies confirmed the relative configurations of 1 and 4 and provided additional support for the structures of 2, 3, and 5.     

In vitro cytotoxic activity of phenanthroindolizidine alkaloids from Cynanchum vincetoxicum and Tylophora tanakae against drug-sensitive and multidrug-resistant cancer cells

Two known phenanthroindolizidine alkaloids, (-)-(R)-13aalpha-antofine (1) and (-)-(R)-13aalpha-6-O-desmethylantofine (2), and two new natural products, (-)-(R)-13aalpha-secoantofine (3) and (-)-(R)-13aalpha-6-O-desmethylsecoantofine (4), were isolated from Cynanchum vincetoxicum. The structures of all compounds were established by means of NMR methods including COSY, NOESY, HSQC, and HMBC experiments, supported by HRMS and optical rotation data. Cytotoxic activity of the isolated alkaloids, and of three other alkaloids previously isolated from Tylophora tanakae, (-)-(R)-13aalpha-tylophorine (5), (-)-(R)-13aalpha-7-O-desmethyltylophorine (6), and (+)-(S)-13abeta-isotylocrebrine (7), was assessed in vitro using a drug-sensitive KB-3-1 and a multidrug-resistant KB-V1 cancer cell line. Structure-activity relationships in this series of alkaloids are discussed. The IC(50) values of some of the alkaloids are in the low nanomolar range, being thus comparable to the activity of clinically used cytotoxic drugs. Previously reported adverse side effects of these alkaloids could possibly be overcome by modern tissue-specific drug targeting techniques.     

樗鸡化学成分的研究

 目的：从樗鸡(Lycorma delicatula White)体中分离制备两种吲哚类生物碱,并鉴定其结构。方法：用溶剂和离子交换柱进行提取和纯化,用制备型高效液相色谱分离制备,用光谱法(¹H-NMR,¹³C-NMR,¹H-¹HCOSY,MS,DEPT)和化学方法对其进行结构鉴定。结果：分离得到两种生物碱,经鉴定其结构分别为 β-育亨宾和阿马里新。结论：两种生物碱在本种昆虫体中均为首次报道。     

Antiophidic solanidane steroidal alkaloids from Solanum campaniforme

Three new solanidane alkaloids bearing a 22,23-epoxy ring (1-3) and four known compounds were isolated from leaves of Solanum campaniforme. The structures were determined using spectroscopic techniques, including 1D and 2D NMR, and HRESIMS experiments. The antiophidic activity of the alkaloids was tested against Bothrops pauloensis venom. Compounds 1-3 completely inhibited myotoxicity without inhibiting phospholipase A2 activity of the venom, while hemorrhage and skin necrosis were significantly reduced in the presence of alkaloids 1 and 2.     

Cytotoxic activity of some phenanthroindolizidine N-oxide alkaloids from Cynanchum vincetoxicum

Two previously known phenanthroindolizidine alkaloids, (-)-10beta-antofine N-oxide (1) and (-)-10beta, 13aalpha-14beta-hydroxyantofine N-oxide (2), and a novel alkaloid, (-)-10beta,13aalpha-secoantofine N-oxide (3), were isolated from aerial parts of Cynanchum vincetoxicum. Their structures were established by means of NMR methods, including COSY, NOESY, HSQC, and HMBC experiments, as well as from their CD spectra. Cytotoxic activity of the alkaloids was assessed in vitro using both a drug-sensitive KB-3-1 and a multi-drug-resistant KB-V1 cancer cell line. The antofine derivatives (1 and 2) showed pronounced cytotoxicity against the drug-sensitive cell line (IC(50) values about 100 nM), whereas the secoantofine derivative (3) was considerably less active. The KB-V1 cell line showed a marginal resistance against all alkaloids, demonstrating that these compounds are poor substrates for the P-glycoprotein (P-170) efflux pump.     

Biologically active aspidofractinine alkaloids from Kopsia singapurensis

Ten new indole alkaloids of the aspidofractinine type, in addition to several recently reported indole alkaloids and 20 other known alkaloids, were obtained from the leaf and stem-bark extract of the Malayan Kopsia singapurensis, viz., kopsimalines A-E (1-5), kopsinicine (6), kopsofinone (7), and kopsiloscines H-J (8-10). The structures of these alkaloids were determined using NMR and MS analysis. Kopsimalines A (1), B (2), C (3), D (4), and E (5) and kopsiloscine J (10) were found to reverse multidrug-resistance in vincristine-resistant KB cells, with 1 showing the highest potency.     

Chemical studies on Mexican plants used in traditional medicine, XV. Sesquiterpene evoninoate alkaloids from Hippocratea excelsa

Three sesquiterpene evoninoate alkaloids, hippocrateine I [1], hippocrateine II [2], and emarginatine A have been isolated from the root and stem barks of Hippocratea excelsa. Compounds 1 and 2 are new naturally occurring substances. The structure of 1 was unequivocally established by X-ray crystallographic analysis, and the structure of the second new alkaloid was deduced by spectral analysis.     

A novel NO-production-inhibiting triterpene and cytotoxicity of known alkaloids from Euonymus laxiflorus

A new triterpene, laxifolone A (1), four known sesquiterpene alkaloids, ebenifoline E-II (2), carigorinine E (3), euojaponine C (4), and emarginatine E (5), and six triterpenoids, 3-hydroxyolean-12-en-22,29-gamma-lactone, 3,11-dioxo-beta-amyrene, 3beta,22alpha-dihydroxyolean-12-en-29-oic acid, 28,29-dihydroxyfriedelan-3-one, 29-hydroxy-3-oxo-D:A-friedooleanan-28-oic acid, and putranjivadione, were isolated from the stems and leaves of Euonymus laxiflorus. Structural elucidations of these compounds were established by spectral analysis. Compound 1 displayed significant nitric oxide (NO) inhibitory effect.