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Special Issue in Honor of Professor Nikolaus (Klaus) Fischer on the Occasion of His 80th Birthday

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (30 June 2017) | Viewed by 38816

Special Issue Editors


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Guest Editor
Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University Graz, Universitätsplatz 4, 8010 Graz, Austria
Interests: chemistry of basal angiosperms; neolignans; GABA receptor; analytical chemistry; honeybee health

Special Issue Information

Dear Colleagues,

This Special Issue is dedicated to Prof. Dr. Nikolaus (Klaus) Fischer, former Professor at the Department of Chemistry, Louisiana State University, and the Department of Pharmacognosy, School of Pharmacy, University of Mississippi, on the occasion of his 80th birthday (celebrated on 8 August, 2016), and in honor of his achievements in phytochemistry.

In view of Klaus’ eminent contributions and indefatigable engagement in our scientific field, we have decided that it is time to dedicate a Special Issue of Molecules to him. Both of the Guest Editors spent wonderful times as post-doctoral researchers in Klaus’ lab more than 20 years ago, and we still feel the spirit of working in “Fischer’s group”. As a true pioneer in phytochemical research (this was made official when he was awarded the title of “Phytochemistry Pioneer” by PSNA (Phytochemical Society of North America) in 2006), Klaus has influenced innumerable researchers in the field over the decades of his academic career, many of whom, as we hope, may contribute to this Special Issue.

Klaus’ long life and career can only be summarized here very briefly. It is great fun, and highly recommended, however, to read his short autobiography that was published in 2007 under the title “Ein Wanderer and Einwanderer in Science” (Phytochemistry, 68, 1838–1841).

He was born in summer of 1936 in a small village in Silesia, a former part of Germany, now belonging to Poland, where his untroubled childhood would only last for a few years. Klaus’ father had to go to war in 1939 and never returned; in 1946, the family had to leave Silesia, then taken by the Russians and later the Polish, with only few belongings, and, after an odyssey in these troubled times, was finally able to settle down in a small village in the northwest of Germany where he went to school and soon discovered his love for chemistry.

After taking a two-year chemical technician’s education, Klaus was able to study chemistry at the University of Tübingen from 1957–1961. In 1965, he obtained his doctorate in the group of G. Opitz, who had come from the group of Nobel Prize winner A. Butenandt. His “American experiences” and actual career as a Natural Product Chemist then began in 1965 when he joined the group of Tom Mabry at the University of Texas in Austin, as a post-doc research fellow. Obviously, being quite successful, after two years, in 1967, Klaus was able to take over an Assistant Professorship at Louisiana State University (LSU). Unfortunately, he had to leave after only one year since he did not have a “green card”, so that he had to go back to Europe for two years. There, he took an assistant’s position in the group of A.S. Dreiding at the University of Zurich. However, his path was directed back to the United States where he was able to obtain a permanent “green card” in 1970 and take back his professorship at LSU, which, from that time on (and promoted to associate (1973) and full professorship (1979) and a chaired professorship (Charles Barré Professor of Chemistry, 1997)), was very successful until his first retirement in 1999. Since Klaus obviously did not want to retire, he took on a new challenge in 1999, when he accepted a call to be a Professor at the Dept. of Pharmacognosy at the University of Mississippi (“Ole Miss”), where he also became the Chair and remained in that position for another four years until his second retirement at the end of 2003. Since then, he has lived with his wife Helga in Denton, Texas, where he recently finished his second book on the history of his home village in Silesia.

Klaus’ over 35 years of Professorship have, not only been very successful and productive (over 200 original papers, many book chapters and a book, 26 PhD students, and innumerable MSc and undergraduate students), but, and this we know from our own experience, has at all times been governed by modesty, by humanness, and friendliness towards all his students, coworkers, and colleagues; one cannot forget his sense of subtle humor, which we all enjoyed and remember very well. Many of us also encountered the warm hospitality of the Fischer´s home, which offered space for scientific and non-scientific discussions, the latter revealing the many non-scientific interests that Klaus also cultivated, and still cultivates. Students, post-docs, and colleagues surely remember the generous atmosphere that Klaus and his wife Helga created, for example, at their “Oktoberfest” or at Thanksgiving.

We, therefore, gladly dedicate this Special Issue to you, Klaus, and we really hope you will enjoy it.

Prof. Dr. Thomas J. Schmidt
Dr. Wolfgang M. Schuehly
Guest Editors

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Published Papers (6 papers)

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Research

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16 pages, 3295 KiB  
Article
Bioinspired Honokiol Analogs and Their Evaluation for Activity on the Norepinephrine Transporter
by Kristen Stout, Marketa Bernaskova, Gary W. Miller, Antje Hufner and Wolfgang Schuehly
Molecules 2018, 23(10), 2536; https://doi.org/10.3390/molecules23102536 - 4 Oct 2018
Cited by 3 | Viewed by 3319
Abstract
In traditional Asian medicinal systems, preparations of the root and stem bark of Magnolia species are widely used to treat anxiety and other nervous disturbances. The biphenyl-type neolignans honokiol and magnolol are the main constituents of Magnolia bark extracts. In the central nervous [...] Read more.
In traditional Asian medicinal systems, preparations of the root and stem bark of Magnolia species are widely used to treat anxiety and other nervous disturbances. The biphenyl-type neolignans honokiol and magnolol are the main constituents of Magnolia bark extracts. In the central nervous system, Magnolia bark preparations that contain honokiol are thought to primarily interact with γ-aminobutyric acid A (GABAA) receptors. However, stress responses inherently involve the noradrenergic system, which has not been investigated in the pharmacological mechanism of honokiol. We present here interactions of honokiol and other synthesized biphenyl-type neolignans and diphenylmethane analogs with the norepinephrine transporter (NET), which is responsible for the synaptic clearance of norepinephrine and the target of many anxiolytics. Of the synthesized compounds, 16 are new chemical entities, which are fully characterized. The 52 compounds tested show mild, non-potent interactions with NET (IC50 > 100 µM). It is thus likely that the observed anxiolytic effects of, e.g., Magnolia preparations, are not due to direct interaction with the noradrenergic system. Full article
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4907 KiB  
Article
Direct Analyses of Secondary Metabolites by Mass Spectrometry Imaging (MSI) from Sunflower (Helianthus annuus L.) Trichomes
by Denise Brentan Silva, Anna-Katharina Aschenbrenner, Norberto Peporine Lopes and Otmar Spring
Molecules 2017, 22(5), 774; https://doi.org/10.3390/molecules22050774 - 10 May 2017
Cited by 22 | Viewed by 7501
Abstract
Helianthus annuus (sunflower) displays non-glandular trichomes (NGT), capitate glandular trichomes (CGT), and linear glandular trichomes (LGT), which reveal different chemical compositions and locations in different plant tissues. With matrix-assisted laser desorption/ionization (MALDI) and laser desorption/ionization (LDI) mass spectrometry imaging (MSI) techniques, efficient methods [...] Read more.
Helianthus annuus (sunflower) displays non-glandular trichomes (NGT), capitate glandular trichomes (CGT), and linear glandular trichomes (LGT), which reveal different chemical compositions and locations in different plant tissues. With matrix-assisted laser desorption/ionization (MALDI) and laser desorption/ionization (LDI) mass spectrometry imaging (MSI) techniques, efficient methods were developed to analyze the tissue distribution of secondary metabolites (flavonoids and sesquiterpenes) and proteins inside of trichomes. Herein, we analyzed sesquiterpene lactones, present in CGT, from leaf transversal sections using the matrix 2,5-dihydroxybenzoic acid (DHB) and α-cyano-4-hydroxycinnamic acid (CHCA) (mixture 1:1) with sodium ions added to increase the ionization in positive ion mode. The results observed for sesquiterpenes and polymethoxylated flavones from LGT were similar. However, upon desiccation, LGT changed their shape in the ionization source, complicating analyses by MSI mainly after matrix application. An alternative method could be applied to LGT regions by employing LDI (without matrix) in negative ion mode. The polymethoxylated flavones were easily ionized by LDI, producing images with higher resolution, but the sesquiterpenes were not observed in spectra. Thus, the application and viability of MALDI imaging for the analyses of protein and secondary metabolites inside trichomes were confirmed, highlighting the importance of optimization parameters. Full article
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383 KiB  
Article
Anti-Trypanosomatid Elemanolide Sesquiterpene Lactones from Vernonia lasiopus O. Hoffm
by Njogu M. Kimani, Josphat C. Matasyoh, Marcel Kaiser, Reto Brun and Thomas J. Schmidt
Molecules 2017, 22(4), 597; https://doi.org/10.3390/molecules22040597 - 8 Apr 2017
Cited by 22 | Viewed by 5790
Abstract
Sleeping sickness or human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) threatening millions of peoples’ lives with thousands infected. The disease is endemic in poorly developed regions of sub-Saharan Africa and is caused by the kinetoplastid “protozoan” parasite Trypanosoma brucei. [...] Read more.
Sleeping sickness or human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) threatening millions of peoples’ lives with thousands infected. The disease is endemic in poorly developed regions of sub-Saharan Africa and is caused by the kinetoplastid “protozoan” parasite Trypanosoma brucei. The parasites are transmitted to humans through bites of infected tsetse flies of the genus Glossina. The few available drugs for treatment of this disease are highly toxic, difficult to administer, costly and unavailable to poor rural communities bearing the major burden of this infection. Therefore, the search for new efficacious, safe and affordable drugs is of high importance. Vernonia lasiopus O. Hoffm., an indigenous African plant of the Asteraceae family, has been extensively reported to be used ethno-medicinally as a treatment for malaria. Its crude extracts obtained with solvents of different polarity were screened in vitro for anti-protozoal activity and the dichloromethane extract was found to be particularly active against Trypanosoma brucei rhodesiense (IC50 = 0.17 µg/mL). Bioassay-guided chromatographic fractionation of the dichloromethane extract led to the isolation and identification of six elemanolide type sesquiterpene lactones: 8-desacylvernolide, vernolepin, vernomenin, vernodalol, vernodalin and 11,13-dihydrovernodalin. All these elemanolide sesquiterpene lactones showed in vitro anti-trypanosomal activity. They were also tested for cytotoxicity against mammalian cells (L6 cell line). Vernolepin, the main component in the extract, was also the most potent with an IC50 value of 0.05 µg/mL against T.b. rhodesiense trypomastigotes. This compound showed a selectivity index of 14.5, which makes it an interesting candidate for in vivo tests and determination of its mechanism of action. Full article
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719 KiB  
Article
New Pesticidal Diterpenoids from Vellozia gigantea (Velloziaceae), an Endemic Neotropical Plant Living in the Endangered Brazilian Biome Rupestrian Grasslands
by Mariana C. Ferreira, Charles L. Cantrell, Stephen O. Duke, Abbas Ali and Luiz H. Rosa
Molecules 2017, 22(1), 175; https://doi.org/10.3390/molecules22010175 - 21 Jan 2017
Cited by 13 | Viewed by 7394
Abstract
Vellozia gigantea is a rare, ancient, and endemic neotropical plant present in the Brazilian Rupestrian grasslands. The dichloromethane extract of V. gigantea adventitious roots was phytotoxic against Lactuca sativa, Agrostis stolonifera, and Lemna paucicostata, and showed larvicidal activity against Aedes [...] Read more.
Vellozia gigantea is a rare, ancient, and endemic neotropical plant present in the Brazilian Rupestrian grasslands. The dichloromethane extract of V. gigantea adventitious roots was phytotoxic against Lactuca sativa, Agrostis stolonifera, and Lemna paucicostata, and showed larvicidal activity against Aedes aegypti. Phytotoxicity bioassay-directed fractionation of the extract revealed one new isopimaradiene, 8(9),15-isopimaradien-1,3,7,11-tetraone, and three new cleistanthane diterpenoids, 7-oxo-8,11,13-cleistanthatrien-3-ol, 3,20-epoxy-7-oxo-8,11,13-cleistanthatrien-3-ol, and 20-nor-3,7-dioxo-1,8,11,13-cleistanthatetraen-10-ol. These new structures are proposed based on interpretation of 1H, 13C, COSY, NOESY, HSQC, and HMBC NMR data. 8(9),15-isopimaradien-1,3,7,11-tetraone was especially phytotoxic with an IC50 value (30 μM) comparable to those of commercial herbicides clomazone, EPTC, and naptalam. In addition, 7-oxo-8,11,13-cleistanthatrien-3-ol provided 100% mortality at a concentration of 125 ppm against one-day-old Ae. aegypti larvae. Our results show that ancient and unique plants, like the endangered narrowly endemic neotropical species V. gigantea present in the Rupestrian grasslands, should also be protected because they can be sources of new bioactive compounds. Full article
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626 KiB  
Article
Assignment of Absolute Configuration of a New Hepatoprotective Schiartane-Type Nortriterpenoid Using X-Ray Diffraction
by Xiaojuan Wang, Frank R. Fronczek, Jiabao Chen, Jiabao Liu, Daneel Ferreira, Shuai Li and Mark T. Hamann
Molecules 2017, 22(1), 65; https://doi.org/10.3390/molecules22010065 - 2 Jan 2017
Cited by 35 | Viewed by 4718
Abstract
A new schiartane-type nortriterpenoid, micrandilactone H was isolated from Kadsura longipedunculata Finet et Gagnep. Its 2D (two dimension) structure was elucidated by NMR spectroscopic analysis, and it is similar to that of Kadnanolactones H and the absolute configuration was established through X-ray diffraction [...] Read more.
A new schiartane-type nortriterpenoid, micrandilactone H was isolated from Kadsura longipedunculata Finet et Gagnep. Its 2D (two dimension) structure was elucidated by NMR spectroscopic analysis, and it is similar to that of Kadnanolactones H and the absolute configuration was established through X-ray diffraction and ECD data analysis. This represents the first complete assignment of the absolute configuration of a schiartane-type nortriterpenoid by X-ray diffraction and the ECD method. Micrandilactone H showed moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells with cell survival rates of 56.84% at 10 μM. Full article
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Review

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4492 KiB  
Review
Review of Ligand Specificity Factors for CYP1A Subfamily Enzymes from Molecular Modeling Studies Reported to-Date
by Jayalakshmi Sridhar, Navneet Goyal, Jiawang Liu and Maryam Foroozesh
Molecules 2017, 22(7), 1143; https://doi.org/10.3390/molecules22071143 - 8 Jul 2017
Cited by 43 | Viewed by 8930
Abstract
The cytochrome P450 (CYP) family 1A enzymes, CYP1A1 and CYP1A2, are two of the most important enzymes implicated in the metabolism of endogenous and exogenous compounds through oxidation. These enzymes are also known to metabolize environmental procarcinogens into carcinogenic species, leading to the [...] Read more.
The cytochrome P450 (CYP) family 1A enzymes, CYP1A1 and CYP1A2, are two of the most important enzymes implicated in the metabolism of endogenous and exogenous compounds through oxidation. These enzymes are also known to metabolize environmental procarcinogens into carcinogenic species, leading to the advent of several types of cancer. The development of selective inhibitors for these P450 enzymes, mitigating procarcinogenic oxidative effects, has been the focus of many studies in recent years. CYP1A1 is mainly found in extrahepatic tissues while CYP1A2 is the major CYP enzyme in human liver. Many molecules have been found to be metabolized by both of these enzymes, with varying rates and/or positions of oxidation. A complete understanding of the factors that govern the specificity and potency for the two CYP 1A enzymes is critical to the development of effective inhibitors. Computational molecular modeling tools have been used by several research groups to decipher the specificity and potency factors of the CYP1A1 and CYP1A2 substrates. In this review, we perform a thorough analysis of the computational studies that are ligand-based and protein-ligand complex-based to catalog the various factors that govern the specificity/potency toward these two enzymes. Full article
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