Neovibsanin A and B are natural products which induced neurite outgrowth in PC12 cells. They belong in the neovibsane class under the rare vibsane natural product family, whose structures are characterized by polycyclic, polyoxygenated cores. Based on a proposed biosynthesis, the synthetic strategy towards neovibsanin A and B involved synthesizing a key enone intermediate. Initial investigation using this intermediate lead to the total synthesis of 2-O-methylneovibsanin H. Crucial to this concise synthesis was an acid-catalyzed, one-pot, four-step cascade reaction. Modifying the reaction condition leads to a different five-step cascade pathway, resulting in the total synthesis of 4,5-bis-epi-neovibsanin A and B. The synthetic trials and tribulations encountered on the road to these final compounds are explored. It is envisaged that other related neovibsane natural products may arise based on this synthetic sequence. 4,5-Bis-epi-neovibsanin A and B, as well as several other structural analogues collected during the synthesis, were biologically assayed using NGF-stimulated PC12 cells. All compounds induced a significant proportion of neurons to extend neurite processes compared to control cultures. The structure-activity relationship studies indicated that the tricyclic core, as well as the 3,3-dimethylacroyl enol ester side chain, may be responsible for promoting a biological response.

Neovibsanin A and B are natural products which induced neurite outgrowth in PC12 cells. They belong in the neovibsane class under the rare vibsane natural product family, whose structures are characterized by polycyclic, polyoxygenated cores. Based on a proposed biosynthesis, the synthetic strategy towards neovibsanin A and B involved synthesizing a key enone intermediate. Initial investigation using this intermediate lead to the total synthesis of 2-O-methylneovibsanin H. Crucial to this concise synthesis was an acid-catalyzed, one-pot, four-step cascade reaction. Modifying the reaction condition leads to a different five-step cascade pathway, resulting in the total synthesis of 4,5-bis-epi-neovibsanin A and B. The synthetic trials and tribulations encountered on the road to these final compounds are explored. It is envisaged that other related neovibsane natural products may arise based on this synthetic sequence. 4,5-Bis-epi-neovibsanin A and B, as well as several other structural analogues collected during the synthesis, were biologically assayed using NGF-stimulated PC12 cells. All compounds induced a significant proportion of neurons to extend neurite processes compared to control cultures. The structure-activity relationship studies indicated that the tricyclic core, as well as the 3,3-dimethylacroyl enol ester side chain, may be responsible for promoting a biological response.

Neovibsanin A and B are natural products which induced neurite outgrowth in PC12 cells. They belong in the neovibsane class under the rare vibsane natural product family, whose structures are characterized by polycyclic, polyoxygenated cores. Based on a proposed biosynthesis, the synthetic strategy towards neovibsanin A and B involved synthesizing a key enone intermediate. Initial investigation using this intermediate lead to the total synthesis of 2-O-methylneovibsanin H. Crucial to this concise synthesis was an acid-catalyzed, one-pot, four-step cascade reaction. Modifying the reaction condition leads to a different five-step cascade pathway, resulting in the total synthesis of 4,5-bis-epi-neovibsanin A and B. The synthetic trials and tribulations encountered on the road to these final compounds are explored. It is envisaged that other related neovibsane natural products may arise based on this synthetic sequence. 4,5-Bis-epi-neovibsanin A and B, as well as several other structural analogues collected during the synthesis, were biologically assayed using NGF-stimulated PC12 cells. All compounds induced a significant proportion of neurons to extend neurite processes compared to control cultures. The structure-activity relationship studies indicated that the tricyclic core, as well as the 3,3-dimethylacroyl enol ester side chain, may be responsible for promoting a biological response.

Neovibsanin A and B are natural products which induced neurite outgrowth in PC12 cells. They belong in the neovibsane class under the rare vibsane natural product family, whose structures are characterized by polycyclic, polyoxygenated cores. Based on a proposed biosynthesis, the synthetic strategy towards neovibsanin A and B involved synthesizing a key enone intermediate. Initial investigation using this intermediate lead to the total synthesis of 2-O-methylneovibsanin H. Crucial to this concise synthesis was an acid-catalyzed, one-pot, four-step cascade reaction. Modifying the reaction condition leads to a different five-step cascade pathway, resulting in the total synthesis of 4,5-bis-epi-neovibsanin A and B. The synthetic trials and tribulations encountered on the road to these final compounds are explored. It is envisaged that other related neovibsane natural products may arise based on this synthetic sequence. 4,5-Bis-epi-neovibsanin A and B, as well as several other structural analogues collected during the synthesis, were biologically assayed using NGF-stimulated PC12 cells. All compounds induced a significant proportion of neurons to extend neurite processes compared to control cultures. The structure-activity relationship studies indicated that the tricyclic core, as well as the 3,3-dimethylacroyl enol ester side chain, may be responsible for promoting a biological response.

This thesis describes the isolation and structure elucidation of ten novel secondary metabolites from one fungus (Pycnoporus cinnabarinus), four lichens (Chrysothrix xanthina, Candelaria concolor, Ramalina glaucescens and Xanthoria parietina), three algae (Plocamium mertensii, Laurencia filiformis and Laurencia elata), two plants (Haemodorum simplex and Dianella callicarpa) and one sponge (Dactylospongia sp). The structures of these isolated compounds were elucidated by a combination of spectroscopic and chemical methods. This thesis also reports two new crystal structures, the identification of two new methylsilylated derivatives as well as the isolation of thirty seven previously reported compounds in which the complete structural assignment by one and two dimensional nuclear magnetic resonance spectroscopy (NMR) has been carried out on known compounds with incomplete or no NMR spectroscopic data. Furthermore, detailed spectroscopic analyses resulted in the re assignment of 1H and 13C chemical shifts for several previously isolated natural products. The biological screening (antimicrobial, antiviral and antitumor assays) of crude extracts and isolated natural products has also been presented. The application of chemical profiling techniques including GCxGC and high pressure liquid chromatography-nuclear magnetic resonance (HPLC-NMR) were utilised to assist with the natural product dereplication process (chemical profiling), monitor chemical degradations in situ and to identify the presence of new natural products and artefacts. In total, fifteen separate terrestrial and marine organisms were investigated.

Orientador: Luciana Francisco Fleuri / Resumo: O processamento de suco de laranja gera grande volume residual, sendo este aproximadamente 50% do fruto. Esses resíduos contêm biomoléculas de interesse industrial tais como as lipases que são capazes de catalisar a hidrólise de glicerídeos e reações de síntese em condições micro-aquosas. A obtenção dessas enzimas diretamente de resíduos reduz os custos de produção e viabiliza diferentes aplicações. As lipases possuem características interessantes como a regioespecificidade e especificidade quanto aos tamanhos da cadeia carbônica de ácidos graxos, possibilitando a geração de produtos diferenciados. Desta forma, o presente trabalho visou, além da obtenção de lipases por meio resíduos de laranja Pera, a aplicação destas em reações capazes de promover mudanças nos substratos (lipídeos) a fim de se obter produtos diferenciados que possam apresentar atividades biológicas. Lipases foram obtidas dos resíduos de laranja Pera e caracterizadas como 1,3 específicas nas frações bagaço, casca e frit as quais apresentaram atividade lipolítica de 55,9 U/g; 58,0 U/g e 49,9 U/g, respectivamente; e da fração polpa como inespecífica com atividade de 40,4 U/g. Essas enzimas foram empregadas em reações de hidrólise e síntese com diferentes óleos vegetais e os produtos de reação analisados quanto às atividades biológicas. Foram obsevadas atividades antioxidante de até 94,87%; atividade antibacteriana sobre E. coli, L. monocytogenes, P. aureginosa, S. enteritidis e S. aureus, e influência sobre a ... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Kohelová E: Alkaloids of Amaryllidaceae family: isolation, structural identification, biological activity. II Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové, 2017, 77p. The aim of the diploma thesis was a preparation of alkaloidal extract from fresh bulbs of Narcissus cv. PROFESSOR EINSTEIN to izolate two Amaryllidaceae alkaloids by column and thin layer chromatography. Subsequently these alkaloids were subjected to structural MS and NMR analysis and tested for biological activity against human cholinesterases (HuAChE and HuBuChE) and for cytotoxic activity. In cooperation with the Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences Prague, antifungal and antimicrobial activities of alkaloids were tested, and in cooperation with Faculdade de Medicina da Universidade de Lisboa Portugal antimalarial activity of alkaloids was studied. Isolated substances were identified as galanthamine, caranine and pluviine. Pluviine was isolated in an amount allowing only structural analysis. In the test for determining cholinesterase inhibitory activity of caranine the following values were obtained: IC50, HuAChE = 320 ± 42 μM a IC50, HuBuChE = 486 ± 56 μM. Galanthamine (IC50,...

Marečková, L .: Biological activity of secondary plant metabolites VII. Alkaloids of Vinca minor L. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Kralove, Hradec Králové, Department of pharmaceutical botany and ecology, Hradec Králové 2018 There was prepared an extract from aerial parts of the plant Vinca minor L. This prepared extract was separated by the column chromatography into individual fractions. One chosen fraction was separated by TLC on silicagel. Two substances were isolated and they we identified by GC/MS and NMR as (-)-minovin and (+)-minovincin. These two substances were tested for their inhibition activity against human acetylcholinesterase (hemolysate of human erythrocytes) and butyrylcholinesterase (human plasma). Their inhibition activity was compared to standards which were Galanthamin, Huperzin A and Eserin. (+)-Minovincin did not show significant inhibitory activity against either enzyme (IC50 = AchE > 1000 µM, BuChE 655,05 ± 35,37 µM) and it is not suitable for further investigation. (-)-Minovin showed no significant activity against AChE (IC50 = 234,27 ± 63,40 µM), activity against BuChE (IC50 = 26,32 ± 2,52 µM) was higher than inhibitory akctivity of Galanthamin, but still relatively low for further investigation. The aim of this work was mainly the...

Schickerová Julie: Alkaloids of Narcissus pseudonarcissus cv. Dutch Master: isolation, structural identification, preparation of analogues, biological activity. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové, 2018, 73 p. The purpose of this diploma thesis was to isolate the substances from the fraction ND 15- 9, which was obtained by column chromatography of the alkaloid extract of Narcissus pseudonarcissus cv. Dutch Master. The method of preparative TLC was used to separate this fraction, and the three purified compounds were isolated in the pure state NDS1-NDS3. NMR, GC/MS and optical rotation were used to determine their structure. The obtained data were compared with data in the literature and further studies on their biological activity were performed. Isolated substances were identified as epimaritidine, crinine and tetrahydromasonine. Their inhibitory activities (IC50, AChE > 1000 μM, IC50, BuChE > 1000 μM) versus human erythrocyte AChE and plasma BuChE were inactive compared to galanthamine standards (IC50, AChE = 1.71 ± 0.07 μM, IC50, BuChE = 42.30 ± 0.10 μM), huperzin A standards (IC50, AChE = 0.033 ± 0.001 μM, IC50, BuChE > 1000 μM) and berberin standards (IC50, AChE = 0.71 ± 0.01 μM, IC50, BuChE = 30.7 ± 3.5...

Klíčová A.: Alkaloids from wood of the species Liriodendron tulipifera L. and their biological activity. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department: Pharmaceutical Botany, Hradec Králové, 2018. Supervisor: PharmDr. Anna Hošťálková, Ph.D. Key words: Liriodendron tulipifera, secondary metabolites, alkaloids, biological activity Alzheimer's disease (AD) is the most common type of dementia. It is neurodegenerative disorder. Patients suffer from cognitive disorder in combination with aphasia, apraxia or disorders of executive functions, which leads to exacerbation of working or social skills. Nowadays, there exist no casual treatment for AD, and that is why the intense research is still waging. Currently there are available remedies, which can slow down progress of AD. These drugs includes also natural substances. An alkaloid extract of Liriodendron tulipifera L. wood showed promising inhibition of human cholinesterases in a preliminary testing. These results were the reason why this extract has been chosen for further isolation of single alkaloids and identification of their biological activity. Isolation was made by column chromatography with step gradient elution. Then was used preparative TLC to isolate single alkaloids. Identification of alkaloids was...