New quinoline alkaloids from the leaves and stems of Orixa japonica, orijanone, isopteleflorine and 3'-O-methylorixine

Orixajaponica (Rutaceae) is a shrub widely distributed in Japan, and has been found to contain various quinoline alkaloids. We investigated the alkaloidal constituents of O. japonica, and four quinoline alkaloids were isolated and characterized. Three of these alkaloids are new natural products.     

Induction of apoptosis by alkaloids, non-protein amino acids, and cardiac glycosides in human promyelotic HL-60 cells

The induction of apoptosis by 66 alkaloids of the quinoline, quinolizidine, pyrrolizidine, isoquinoline, indole, terpene, tropane, steroid, purine, and piperidine type, of 9 cardiac glycosides, 11 non-protein amino acids and 10 further secondary metabolites was assayed in HL-60 cell cultures and measured by quantification of the subdiploid DNA content by flow cytometry, detection of DNA fragmentation by gel electrophoresis, and cell morphology. Several alkaloids of the isoquinoline, quinoline, and indole type were active, whereas quinol-izidine, tropane, pyrrolizidine, terpene and piperdine alkaloids were mostly inactive. The proapoptotic alkaloids can be characterized by their property to inhibit protein biosynthesis and their intercalation into DNA at the same time, or by their inhibition of microtubule formation. All cardiac glycosides, which are both membrane detergents and Na+,K+-ATPase inhibitors, are potent apoptosis inducers. Also proapoptotic were a few non-protein amino acids, podophyllotoxin and the flavonoid quercetin.     

Furomegistines I and II, two furanopyridine alkaloids from the bark of Sarcomelicope megistophylla

Two alkaloids, furomegistine I (1) and furomegistine II (2), were isolated from the bark of Sarcomelicope megistophylla. Their structures have been elucidated on the basis of MS and NMR data. Both belong to the category of furanopyridine alkaloids and should be considered as oxidation products of a furo[2,3-b]quinoline precursor. The two alkaloids exhibited moderate cytotoxic activity.     

Alkaloids and phenylpropanoids from Peganum nigellastrum

Two canthin-6-one alkaloids, luotonins C and D, and two phenylpropanoids, dihydrosinapyl ferulate and dihydroconiferyl ferulate, were isolated from the aerial parts of Peganum nigellastrum along with four known alkaloids, harmine, 3-phenylquinoline, 3-(4-hydroxyphenyl)quinoline and 3-(1H-indol-3-yl)quinoline. Their structures were elucidated by spectroscopic techniques. The structures of luotonins C and D were also confirmed by chemical synthesis.     

Furoquinoline alkaloids from the southern African Rutaceae Teclea natalensis

The chloroform and ethyl acetate extracts of the leaves of Teclea natalensis have yielded two furoquinoline alkaloids, 6-[(2,3-epoxy-3-methylbutyl)oxy]-4,7-dimethoxyfuro[2,3-b]quinoline and 4,7-dimethoxy-6-[(3-methyl-2-butenyl)oxy]furo[2,3-b]quinoline, and the known alkaloids 4,7-dimethoxy-8-[(3-methyl-2-butenyl)oxy]furo[2,3-b]quinoline, flindersiamine and dictamnine.     

Recent advances in the fight against leishmaniasis with natural products

The active compounds obtained from some medicinal plants used traditionally worldwide for the treatment of leishmaniasis are reviewed. Among these active molecules, described in recent literature are quinoline alkaloids such as alkyl-2 quinoline and aryl-2 quinoline from Galipea longiflora, isoquinoline alkaloids such as isoguattouregidine from Guatteria foliosa, indole alkaloids such as conodurine and gabunine from Pescheiera van heurkii, terpenes such as jatrogrossidione from Jatropha grossidentata, acetogenins such as senegalene from Annona senegalensis and lignans such as (+)nyasol from Asparagus africanus. Other natural compounds with antileishmanial activity are coumarins, chalcones, lactones, tetralones and saponins. Some of them are known antiprotozoal natural products. These compounds could be used as templates to discover new and effective drugs against leishmaniasis.     

Crystal and molecular structures of trichloro-cobalt(II) complexes of epiquinine, epiquinidine, and epidihydrocinchonine

Cinchona alkaloids are very well known antimalarials but the mechanism of their biological action still remains to be elucidated. The structural studies of active erythro and inactive threo alkaloid complexes are an important step to this aim. In this paper results of crystal structure analysis of three cobalt complexes of threo alkaloids are presented: (epiquininium)trichlorocobalt(II) (EpiQnCoCl3), (epiquinidinium)trichlorocobalt(II) (EpiQdCoCl3) and (epidihydrocinchoninium)trichlorocobalt(II) (EpiCnCoCl3). The complexes are zwitterions in which trichlorocobalt substituents are coordinated to quinoline nitrogen atoms and quinuclidine nitrogen atoms are protonated. EpiQnCoCl3 adopts uncommon conformation with quinoline moiety oriented in the opposite direction in comparison to the analogous uncomplexed alkaloid. The packing in the crystal structures is determined mainly by the hydrogen bonds, in which the chlorine atoms of substituents and solvent molecules contribute. Atoms participating in hydrogen bonds in EpiQnCoCl3 and EpiQdCoCl3 form large rings, while in EpiCnCoCl3 only chains are present. Solvent molecules are very important for the packing mode. In contrast to most erythro alkaloids, the hydroxyl oxygen atom in the title complexes forms weak or not well defined hydrogen bonds. The contribution of very weak intramolecular interactions N1--H1...O12 cannot be excluded. Such "trace" interactions can be considered a relic of the unprotonated status of an epi alkaloid.     

Aaptolines A and B,Two New Quinoline Alkaloids from the Marine Sponge Aaptos aaptos

Two new quinoline alkaloids, aaptolines A and B, were isolated from the marine sponge Aaptos aaptos. Their structures were determined by HR‐ESI‐MS data, NMR analysis, and X‐ray crystallography. Structurally, aaptoline A is characterized as having a quinoline skeleton fused with a 1,4‐dioxane motif at the C(7)?C(8) position, whereas aaptoline B possessed an intriguing 1H‐pyrrolo[2,3‐g]quinoline moiety. The cytotoxic assay of these compounds showed no cytotoxicity towards HepG2, A549, and PC9 cancer cell lines and had IC₅₀ values greater than 20 μm .     

Beta-carboline and quinoline alkaloids in root cultures and intact plants of Peganum harmala

Alkaloid profiles of root and shoot cultures, seedlings and mature plants were analysed by capillary GLC and GLC-MS. beta-Carboline alkaloids, such as harmine, harmaline dominate in normal and root cultures transformed by Agrobacterium rhizogenes, as well as in roots and fruits of the plant. In shoots, flowers and shoot cultures quinoline alkaloids such as peganine, deoxypeganine, vasicinone and deoxyvasicinone widely replace the beta-carboline alkaloids. In root cultures, the formation of beta-carboline alkaloids can be induced by methyljasmonate and several other elicitors indicating that these alkaloids are part of the reactive chemical defence system of Peganum harmala.     

Effect of auxin on cytodifferentiation and production of quinoline alkaloids in compact globular structures of Cinchona ledgeriana

Fine cell suspension cultures of Cinchona ledgeriana produce only very low amounts of quinoline alkaloids. These cultures formed self-propagating compact globular structures (CGS) on medium containing 2,4-D and BAP. These CGS could be induced to produce significant amounts of quinoline alkaloids by replacing 2,4-D by low amounts of 1-NAA, which was accompanied by histological changes of the CGS. A few high producing CGS clones could be selected. The stability of this trait was studied over a period of about one year of culture in maintenance medium.Abbreviations BAP Benzylaminopurine - 2,4-D 2,4-Dichlorophenoxyacetic acid - 1-NAA 1-Naphthylacetic acid - CGS compact globular structures     

Quinoline alkaloids as intercalative topoisomerase inhibitors

Quinoline alkaloids are abundant in the Rutaceae, and many have exhibited cytotoxic activity. Because structurally related antitumor alkaloids such as camptothecin and fagaronine are known to function as intercalative topoisomerase poisons, it is hypothesized that cytotoxic Stauranthus alkaloids may also serve as intercalative topoisomerase inhibitors. To test this hypothesis theoretically, ten Stauranthus quinoline alkaloids were examined for potential intercalation into DNA using a molecular docking approach. Four of the alkaloids (stauranthine, skimmianine, 3′,6′-dihydroxy-3′,6′-dihydrostauranthine, and trans-3′,4′-dihydroxy-3′,4′-dihydrostauranthine) were able to intercalatively dock consistently into DNA. In order to probe the intermolecular interactions that may be responsible for intercalation of these quinoline alkaloids, density functional calculations have been carried out using both the B3LYP and M06 functionals. M06 calculations indicated favorable π–π interactions between either skimmianine or stauranthine and the guanine–cytosine base pair. Furthermore, the lowest-energy face-to-face orientation of stauranthine with guanine is consistent with favorable dipole–dipole orientations, favorable electrostatic interactions, and favorable frontier molecular orbital interactions. Likewise, the lowest-energy face-to-face orientation of stauranthine with the guanine–cytosine base pair reveals favorable electrostatic interactions as well as frontier molecular orbital interactions. Thus, not only can quinoline alkaloids dock intercalatively into DNA, but the docked orientations are also electronically favorable.      

Synthesis, analytical behaviour and biological evaluation of new 4-substituted pyrrolo[1,2-a]quinoxalines as antileishmanial agents

An original series of 4-substituted pyrrolo[1,2-a]quinoxaline derivatives, new structural analogues of Galipea species quinoline alkaloids, was synthesized from various substituted 2-nitroanilines via multistep heterocyclizations and tested for in vitro antiparasitic activity upon Leishmania amazonensis and Leishmania infantum strains. Structure-activity relationships enlighten the importance of the 4-substituted alkenyl side chain on the pyrrolo[1,2-a]quinoxaline moiety to modulate the antileishmanial activity.     

粉花绣线菊复合群的化学分类研究

以粉花绣线菊复合群中二萜及二萜生物碱的结构特征,仿生合成及化学的相关性为基础,结合地理分布以及细胞学和形态学方面的研究资料,讨论粉花经菊复合群的化学分类,（１）具缩醛和二萜可能是绣线菊二萜生物碱的生源合成前体,（２）粉花绣线菊复合群是绣线菊属中特殊的,相对独立的类群;（３）我国西南尤其是横断山区是该复合群近代分化中心,有要能是起源中心;（４）对某些变种进行归并。     

Influence of production media on Cinchona cell cultures; spontaneous formation of β-carbolines from L-tryptophan

Evidence is presented that the β-carboline alkaloids norharman and harman are artifacts formed from L-tryptophan. Transfer of Cinchona ledgeriana suspension cultured cells to Zenk's alkaloid production medium (ZAP medium) resulted in cell death. No quinoline or terpenoid indole alkaloids were formed. However, the L-tryptophan present in the production medium was transformed to the β-carboline alkaloids, harman and norharman. It was demonstrated that norharman was also formed in ZAP medium without cells and in ZAP medium containing frost-killed cell material.     

Mechanism of action of some quinoline alkaloids on respiratory chain of mitochondria]

The mechanism of action of some quinoline alkaloids and their derivatives on respiratory chain of rat liver and Candida lipolytica yeast mitochondria was studied. The alkaloids were shown to inhibit electron transfer in the respiratory chain. The site of their action is localized between b and c cytochromes. Besides their ability to inhibit electron transfer in the respiratory chain, alkaloids are shown to be specific inhibitors of "exogenous" NADH-dehydrogenase of C. lipolytica yeast mitochondria. In addition to their inhibiting properties alkaloids can stimulate ATPase activity of mitochondria. O-alkylation of pseudane-IX permits to differentiate the inhibiting and uncoupling properties of this alkaloid.     

Stereochemical aspects of the biological oxidation of aryl isoprenoids. The asymmetric synthesis and absolute configuration of meranzin and of meranzin hydrate

The role of epoxides in the biological oxidation of aryl prenyl derivatives is discussed in terms of the stereochemistry of quinoline alkaloids and coumarins found in species of the Rutaceae and Umbelliferae. Asymmetric synthesis of the epoxide, meranzin and of the diol, meranzin hydrate, have been carried out and the absolute configurations of the two coumarins have been established.     

Quinoline alkaloids from Acronychia laurifolia.

Bioassay-directed fractionation of a root extract of Acronychia laurifolia (Rutaceae) using the KB-V1+ human tumor cell line led to the isolation of six quinoline alkaloids. One of these alkaloids is novel, namely, 2,3-methylenedioxy-4,7-dimethoxyquinoline and the other five were identified as the known compounds, evolitrine, gamma-fagarine, skimmianine, kokusaginine and maculosidine. Two known bis-tetrahydrofuran lignans, sesamolin and yangambin, were also identified. The structure of the new alkaloid was determined by spectroscopic methods. All of the isolates were evaluated against a panel of human cancer cell lines; four of the alkaloids showed weak cytotoxic activity.     

Two New Diterpenoid Alkaloids from Spiraea japonica L.f.var. Fortunei (Planchon) Rehd.

Two new hetisine-type C20-diterpenoid alkaloids named spiraqine (1) and 6-hydroxylspiraqine (2), and four known alkaloids, namely spiredine (3), spiradine A (4), spiradine B (5), and spirasine Ⅴ/Ⅵ (6),were isolated from Spiraea japonica L. f. var. fortunei (Planchon) Rehd. The structures of the alkaloids were elucidated using nuclear magnetic resonance analysis (1H-NMR, 13C-NMR, DEPT, HMQC, and HMBC) and mass spectrometry data.     

Polyhydroxylated pyrrolidine and piperidine alkaloids from Adenophora triphylla var. japonica (Campanulaceae)

Adenophora triphylla var. japonica (Campanulaceae) yielded two new alkaloids, the 6-C-butyl derivative of 2R,5R-bis(hydroxymethyl)-3R,4R-dihydroxypyrrolidine (DMDP) and alpha-1-C-ethyl-fagomine, together with the known alkaloids 1,4-dideoxy-1,4-imino-D-arabinitol, 1-deoxynojirimycin, and 1-deoxymannojirimycin. 6-C-Butyl-DMDP showed inhibitory activity toward almond beta-glucosidase (IC50 = 68 microM), whereas alpha-1-C-ethyl-fagomine inhibited bovine liver beta-galactosidase (IC50 = 29 microM).