http://www.mdpi.com/journal/molecules/special_issues/alkaloids/ Manuscripts should be prepared according to the Instructions for Authors and submitted by e-mail to molecules@mdpi.org, with a copy to the Guest Editor Prof. Dr. Patrícia Valentao, E-mail: valentao@ff.up.pt, Prof. Dr. Mariana Sottomayor, E-mail: msottoma@ibmc.up.pt, and the Editor-in-Chief, Dr. Derek J. McPhee, E-mail: mcphee@mdpi.org. The subject title of the message should be "Manuscript Submission for Special Issue on Alkaloids". Deadline for article submission: 30 June 2008 (Papers can be continuously submitted, processed, and if accepted, continuously published). http://www.mdpi.com/1420-3049/13/12/3198/ Peptic ulcer disease is a deep gastrointestinal erosion disorder that involves the entire mucosal thickness and can even penetrate the muscular mucosa. Numerous natural products have been evaluated as therapeutics for the treatment of a variety of diseases, including this one. These products usually derive from plant and animal sources that contain active constituents such as alkaloids, flavonoids, terpenoids, tannins and others. The alkaloids are natural nitrogen-containing secondary metabolites mostly derived from amino acids and found in about 20% of plants. There has been considerable pharmacological research into the antiulcer activity of these compounds. In this work we review the literature on alkaloids with antiulcer activity, which covers about sixty-one alkaloids, fifty-five of which have activity against this disease when induced in animals. http://www.mdpi.com/1420-3049/13/12/3198/ Wed, 17 Dec 2008 00:00:00 CET Molecules 2008-12-17 13 12 Review 3198 3223 1420-3049 Gastric and Duodenal Antiulcer Activity of Alkaloids: A Review 2008-12-17 doi: 10.3390/molecules13123198 Heloina de Sousa Falcão Jacqueline Alves Leite José Maria Barbosa-Filho Petrônio Filgueiras de Athayde-Filho Maria Célia de Oliveira Chaves Marcelo Dantas Moura Anderson Luiz Ferreira Ana Beatriz Albino de Almeida Alba Regina Monteiro Souza-Brito Margareth de Fátima Formiga Melo Diniz Leônia Maria Batista http://www.mdpi.com/1420-3049/13/10/2462/ The potential induction of a programmed cell death (PCD) in Trypanosoma b. brucei by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene, tropane, steroid, and piperidine type was studied by measuring DNA fragmentation and changes in mitochondrial membrane potential. For comparison, the induction of apoptosis by the same alkaloids in human leukemia cells (Jurkat APO-S) was tested. Several alkaloids of the isoquinoline, quinoline, indole and steroidal type (berberine, chelerythrine, emetine, sanguinarine, quinine, ajmalicine, ergotamine, harmine, vinblastine, vincristine, colchicine, chaconine, demissidine and veratridine) induced programmed cell death, whereas quinolizidine, tropane, terpene and piperidine alkaloids were mostly inactive. Effective PCD induction (EC50 below 10 µM) was caused in T. brucei by chelerythrine, emetine, sanguinarine, and chaconine. The active alkaloids can be characterized by their general property to inhibit protein biosynthesis, to intercalate DNA, to disturb membrane fluidity or to inhibit microtubule formation. http://www.mdpi.com/1420-3049/13/10/2462/ Fri, 03 Oct 2008 00:00:00 CEST Molecules 2008-10-03 13 10 Article 2462 2473 1420-3049 Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei) 2008-10-03 doi: 10.3390/molecules13102462 Vera Rosenkranz Michael Wink http://www.mdpi.com/1420-3049/13/8/1875/ Strictosidine, the precursor of more than 2,500 indole alkaloids, was isolated from four species of three plant families. By searching the Dictionary of Natural Products on DVD it was found that about 150 indole alkaloids were obtained from the same species (coalkaloids), which is a direct proof of their common origin. On the base of their threedimensional structure, taxonomic properties and standard reaction mechanisms an extended network was established which involved the four fundamental skeletons, the three types of carbon framework in the secologanin subunit and all major groups of indole alkaloids derived from secologanin and tryptamine (except a few minor groups, in which only less then 10 alkaloids were known). The system was extended to the heterodimer indole alkaloids and the quinoindole alkaloids as well. http://www.mdpi.com/1420-3049/13/8/1875/ Wed, 27 Aug 2008 00:00:00 CEST Molecules 2008-08-27 13 8 Review 1875 1896 1420-3049 Rigorous Biogenetic Network for a Group of Indole Alkaloids Derived from Strictosidine 2008-08-27 doi: 10.3390/molecules13081875 László F. Szabó http://www.mdpi.com/1420-3049/13/8/1722/ Scopolamine is an alkaloid widely used in medicine for its anticholinergic activity. The aim of this review is to show that metabolic engineering techniques constitute a suitable tool to improve the production of tropane alkaloids, focusing in particular on scopolamine. We present an overview of results obtained by various research groups, including our own, who have studied the overexpression of genes involved in the biosynthesis of scopolamine in different plant species that produce tropane alkaloids. Experiments carried out to improve production in hairy root cultures will also be described, as well as those attempting to biotransform hyoscyamine into scopolamine in roots and transgenic tobacco cells. http://www.mdpi.com/1420-3049/13/8/1722/ Mon, 18 Aug 2008 00:00:00 CEST Molecules 2008-08-18 13 8 Review 1722 1742 1420-3049 Application of Metabolic Engineering to the Production of Scopolamine 2008-08-18 doi: 10.3390/molecules13081722 Javier Palazón Arturo Navarro-Ocaña Liliana Hernandez-Vazquez Mohammad Hossein Mirjalili http://www.mdpi.com/1420-3049/13/8/1584/ A simple, rapid, solvent-free, room temperature one pot synthesis of benzene ring acylated and demethylated analogues of harmine using acyl halides/acid anhydrides and AlCl3 has been developed. Eight different acyl halides/acid anhydrides were used in the synthesis. The resulting mixture of products was separated by column chromatography to afford 10- and 12-monoacyl analogues, along with 10,12-diacyl-11-hydroxy products. In five cases the corresponding 10-acyl-11-hydroxy analogues were also obtained. Yields from the eight syntheses (29 products in total) were in the 6-34% range and all compounds were fully characterized. http://www.mdpi.com/1420-3049/13/8/1584/ Wed, 06 Aug 2008 00:00:00 CEST Molecules 2008-08-06 13 8 Article 1584 1598 1420-3049 A Simple, Rapid and Mild One Pot Synthesis of Benzene Ring Acylated and Demethylated Analogues of Harmine under Solvent-free Conditions 2008-08-06 doi: 10.3390/molecules1301584 Sabira Begum Syed Nawazish Ali Farhat Farhat Syed Imran Hassan Bina S. Siddiqui http://www.mdpi.com/1420-3049/13/7/1518/ Pilocarpine, an important imidazole alkaloid, is extracted from the leaves of Pilocarpus microphyllus (Rutaceae), known in Brazil as jaborandi and used mainly for the treatment of glaucoma. Jaborandi leaves also contain other imidazole alkaloids, whose pharmacological and physiological properties are unknown, and whose biosynthetic pathways are under investigation. In the present study, a HPLC method coupled with ESI-MSn was developed for their qualitative and quantitative analysis. This method permits the chromatographic separation of the imidazole alkaloids found in extracts of jaborandi, as well as the MS/MS analysis of the individual compounds. Thus two samples: leaves of P. microphyllus and a paste that is left over after the industrial extraction of pilocarpine; were compared. The paste was found to contain significant amounts of pilocarpine and other imidazole alkaloids, but had a slightly different alkaloid profile than the leaf extract. The method is suitable for the routine analysis of samples containing these alkaloids, as well as for the separation and identification of known and novel alkaloids from this family, and may be applied to further studies of the biosynthetic pathway of pilocarpine in P. microphyllus. http://www.mdpi.com/1420-3049/13/7/1518/ Wed, 30 Jul 2008 00:00:00 CEST Molecules 2008-07-30 13 7 Article 1518 1529 1420-3049 HPLC-ESI-MS/MS of Imidazole Alkaloids in Pilocarpus microphyllus 2008-07-30 doi: 10.3390/molecules13071518 Alexandra Sawaya Ilka Nacif Abreu Nathalia Luiza Andreazza Marcos N. Eberlin Paulo Mazzafera http://www.mdpi.com/1420-3049/13/7/1465/ Chemical analysis of the secondary metabolites of the Caribbean sponge Plakortis simplex, a source of many bioactive compounds, showed the presence of the new metabolite simplexidine (4), belonging to the extremely rare class of 4-alkyl-pyridinium alkaloids. The structural characterization of this molecule, based on spectroscopic methods, is reported. http://www.mdpi.com/1420-3049/13/7/1465/ Thu, 17 Jul 2008 00:00:00 CEST Molecules 2008-07-17 13 7 Article 1465 1471 1420-3049 Simplexidine, a 4-Alkylpyridinium Alkaloid from the Caribbean Sponge Plakortis simplex 2008-07-17 doi: 10.3390/molecules13071465 Ernesto Fattorusso Adriana Romano Fernando Scala Orazio Taglialatela-Scafati http://www.mdpi.com/1420-3049/13/2/475/ The effects of anonaine, an aporphine isoquinoline alkaloid, on dopaminebiosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Anonaineat concentration ranges of 0.01-0.2 μM showed a significant inhibition of dopaminecontent at 24 h, with an IC50 value of 0.05 μM. Anonaine at 0.05 μM inhibited tyrosinehydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) activities to 38.4-40.2% and 78.4-90.2% of control levels at 12-24 h and 3-6 h, respectively. TH activity wasmore influenced than AADC activity. Anonaine also decreased intracellular cyclic AMPlevels, but not intracellular Ca2+ concentrations. In addition, anonaine (0.05 μM) reducedL-DOPA (50 μM and 100 μM)-induced increases in dopamine content at 24 h. However,anonaine (0.05 μM) did not enhance L-DOPA (50 μM and 100 μM)-induced cell death 476after 24 h. These results suggest that anonaine inhibits dopamine biosynthesis by mainlyreducing TH activity without aggravating L-DOPA-induced cytotoxicity in PC12 cells. http://www.mdpi.com/1420-3049/13/2/475/ Wed, 27 Feb 2008 00:00:00 CET Molecules 2008-02-27 13 2 Article 475 487 1420-3049 Effects of Anonaine on Dopamine Biosynthesis and L-DOPA-Induced Cytotoxicity in PC12 Cells 2008-02-27 doi: 10.3390/molecules13020475 Jae Joon Lee Chun Mei Jin Young Kyoon Kim Shi Yong Ryu Sung Cil Lim Myung Koo Lee http://www.mdpi.com/1420-3049/13/2/272/ Rutaecarpine is an indolopyridoquinazolinone alkaloid isolated from Evodiarutaecarpa and related herbs, which has shown a variety of intriguing biological propertiessuch as anti-thrombotic, anticancer, anti-inflammatory and analgesic, anti-obesity andthermoregulatory, vasorelaxing activity, as well as effects on the cardiovascular andendocrine systems. Recent progress in the studies on the isolation, synthesis, structureactivityrelationship studies, biological activities and metabolism of rutaecarpine arereviewed. http://www.mdpi.com/1420-3049/13/2/272/ Wed, 06 Feb 2008 00:00:00 CET Molecules 2008-02-06 13 2 Review 272 300 1420-3049 Progress in the Studies on Rutaecarpine 2008-02-06 doi: 10.3390/molecules13020272 Seung Ho Lee Jong-Keun Son Byeong Seon Jeong Tae-Cheon Jeong Hyeon Wook Chang Eung-Seok Lee Yurngdong Jahng http://www.mdpi.com/1420-3049/13/1/3/ Sparteine N1-oxide and α-isosparteine N-oxide were prepared and theirstructures determined for the first time by 1H- and 13C-NMR spectroscopy using twodimensionaltechniques. The N-oxide effects were also calculated. http://www.mdpi.com/1420-3049/13/1/3/ Wed, 09 Jan 2008 00:00:00 CET Molecules 2008-01-09 13 1 Communication 3 10 1420-3049 NMR Spectra of Sparteine N1-oxide and α-Isosparteine N-oxide 2008-01-09 doi: 10.3390/molecules13010003 Beata Jasiewicz