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Carbohydrates Carbohydrates 2018 • Amélia Rauter and Pilar Nuno Manuel Xavier Carbohydrates 2018 Edited by Amélia Pilar Rauter and Nuno Manuel Xavier Printed Edition of the Special Issue Published in Pharmaceuticals www.mdpi.com/journal/pharmaceuticals Carbohydrates 2018 Carbohydrates 2018 Special Issue Editors Am´elia Pilar Rauter Nuno Manuel Xavier MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin Special Issue Editors Amelia´ Pilar Rauter Nuno Manuel Xavier Universidade de Lisboa Universidade de Lisboa Portugal Portugal Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Pharmaceuticals (ISSN 1424-8247) (available at: https://www.mdpi.com/journal/pharmaceuticals/ special issues/carbohydrates2018). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03928-316-3 (Pbk) ISBN 978-3-03928-317-0 (PDF) c 2020 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Special Issue Editors ..................................... vii Am´elia Pilar Rauter and Nuno Manuel Xavier Special Issue “Carbohydrates 2018” Reprinted from: Pharmaceuticals 2020, 13, 5, doi:10.3390/ph13010005 ................ 1 Lu´ıs O. B. Zamoner, Valquiria Arag˜ao-Leoneti and Ivone Carvalho Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities Reprinted from: Pharmaceuticals 2019, 12, 108, doi:10.3390/ph12030108 ............... 3 Nuno M. Xavier, Eduardo C. de Sousa, Margarida P. Pereira, Anne Loesche, Immo Serbian, Ren´e Csuk and M. Concei¸c˜ao Oliveira Synthesis and Biological Evaluation of Structurally Varied 5 -/6 -Isonucleosides and Theobromine-Containing N-Isonucleosidyl Derivatives Reprinted from: Pharmaceuticals 2019, 12, 103, doi:10.3390/ph12030103 ............... 17 Ana M. de Matos, Alice Martins, Teresa Man, David Evans, Magnus Walter, Maria Concei¸c˜ao Oliveira, Oscar´ L´opez, Jos´e G. Fernandez-Bolanos, ˜ Philipp D¨atwyler, Beat Ernst, M. Paula Macedo, Marialessandra Contino, Nicola A. Colabufo and Am´elia P. Rauter Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential β Against H2O2- and A 1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells Reprinted from: Pharmaceuticals 2019, 12, 98, doi:10.3390/ph12020098 ................ 39 Juan C. Est´evez, Marcos A. Gonz´alez, M. Carmen Villaverde, Yuki Hirokami, Atsushi Kato, Fredy Sussman, David Reza and Ram´on J. Est´evez Chain-Branched Polyhydroxylated Octahydro-1H-Indoles as Potential Leads against Lysosomal Storage Diseases Reprinted from: Pharmaceuticals 2019, 12, 47, doi:10.3390/ph12020047 ................ 57 Katherine McReynolds, Dustin Dimas, Grace Floyd and Kara Zeman Development of a Microwave-assisted Chemoselective Synthesis of Oxime-linked Sugar Linkers and Trivalent Glycoclusters Reprinted from: Pharmaceuticals 2019, 12, 39, doi:10.3390/ph12010039 ................ 71 Patr´ıcia Batista, Pedro Castro, Ana Raquel Madureira, Bruno Sarmento and Manuela Pintado Development and Characterization of Chitosan Microparticles-in-Films for Buccal Delivery of Bioactive Peptides Reprinted from: Pharmaceuticals 2019, 12, 32, doi:10.3390/ph12010032 ................ 85 Michelle M. Kuttel and Neil Ravenscroft Conformation and Cross-Protection in Group B Streptococcus Serotype III and Streptococcus pneumoniae Serotype 14: A Molecular Modeling Study Reprinted from: Pharmaceuticals 2019, 12, 28, doi:10.3390/ph12010028 ................101 Farzana Hossain and Peter R. Andreana Developments in Carbohydrate-Based Cancer Therapeutics Reprinted from: Pharmaceuticals 2019, 12, 84, doi:10.3390/ph12020084 ................119 Rachel Hevey Strategies for the Development of Glycomimetic Drug Candidates Reprinted from: Pharmaceuticals 2019, 12, 55, doi:10.3390/ph12020055 ................137 v About the Special Issue Editors Am´elia Pilar Rauter is Full Professor of Organic Chemistry and the President of the Department of Chemistry and Biochemistry of Faculdade de Ciencias,ˆ Universidade de Lisboa (Cienciasˆ ULisboa), and the Coordinator of the Carbohydrate Chemistry Group (Group 11) of the Centro de Qu´ımica Estrutural (CQE). She is the President of the International Carbohydrate Organisation and the Secretary of the European Carbohydrate Organisation, and serves IUPAC as Vice-President of the IUPAC Division of Organic and Biomolecular Chemistry, as Titular Member of IUPAC Division of Chemical Nomenclature and Structure Representation and as Associate Member of its Interdivisional Committee on Terminology, Nomenclature and Symbols. She is the founder of the Portuguese Chemical Society Carbohydrate Group. Her research covers the development of new carbohydrate-based molecular entities for the treatment/prevention of metabolic (diabetes), degenerative diseases (Alzheimer’s and Prion diseases, cancer), and infection, either inspired in nature or accessed through rational design and synthesis. She is Editor of the Royal Society of Chemistry Carbohydrate Chemistry book series, Associated Editor of the Mediterranean Journal of Chemistry, and member of journals advisory/editorial boards in Medicinal/Organic/Carbohydrate Chemistry, namely the European Journal of Organic Chemistry (Wiley), Medicinal Chemistry (Bentham Science), Pharmaceuticals (MDPI), Journal of Carbohydrate Chemistry (Taylor & Francis), among others. She has published more than 150 papers and book chapters, authored 8 granted patents and has been invited as speaker of national and international meetings e.g., Gordon Conference, ECO and ICS meetings. Among her honors, she was awarded with the Mention of Excellency by Faculdade de Ciencias,ˆ Universidade de Lisboa since 2007, she is Fellow of the Royal Society of Chemistry and received the Madinaveitia-Lourenc¸o Prize given by the Spanish Royal Chemical Society in 2017. Nuno Manuel Xavier (Dr.) is a Researcher at Centro de Qu´ımica Estrutural (CQE), Faculdade de Ciencias,ˆ Universidade de Lisboa (Cienciasˆ Ulisboa). He received a double PhD degree in Chemistry (Organic Chemistry) from the University of Lisbon and from the National Institute of Applied Sciences of Lyon in 2011. He was then a Postdoctoral Research Fellow at the University of Natural Resources and Life Sciences of Vienna and afterwards a post-Doc at Prof. Rauter Carbohydrate Chemistry Group at Cienciasˆ ULisboa. In 2014 he was awarded an Investigator Starting Grant at Cienciasˆ ULisboa and recently he has been selected as Assistant Researcher at CQE, both of which under highly competitive calls from the Portuguese Foundation for Science and Technology (FCT). His research has been devoted to the development of efficient synthetic methodologies for novel bioactive carbohydrate-based molecules, for which he has been internationally recognized with various Young Scientist Awards (e.g., IUPAC, Alberta Ingenuity Centre for Carbohydrate Science - Canada, Groupe Lyonnais des Glyco-Sciences - France) and an Innovation Award at the International Carbohydrate Symposium 2018. He has been particularly focused on medicinal chemistry of nucleos(t)ides towards new therapeutic lead compounds. He was the PI of an FCT-funded R&D exploratory project and Team Member of 8 projects funded by national or international entities. His research activities have been reported in ca. 40 publications and he has been Speaker of more than 30 lectures in international and national Symposia. vii pharmaceuticals Editorial Special Issue “Carbohydrates 2018” Amélia Pilar Rauter 1,2,* and Nuno Manuel Xavier 1,2 ◦ 1 Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Ed. C8, 5 Piso, Campo Grande, 1749-016 Lisboa, Portugal; [email protected] ◦ 2 Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Ed. C8, 5 Piso, Campo Grande, 1749-016 Lisboa, Portugal * Correspondence: [email protected] Received: 20 December 2019; Accepted: 20 December 2019; Published: 29 December 2019 This special issue of Pharmaceuticals has been dedicated to Carbohydrates on the occasion of the 29th International Carbohydrate Symposium, held at the Universidade de Lisboa from 15–19 July 2018. Recent findings and trends in carbohydrate science are presented and discussed in its nine articles. They are demonstrative of the relevance of carbohydrate research in medicinal chemistry and pharmaceutical sciences, and of the exciting opportunities that carbohydrate-based structures offer for the discovery of new solutions for therapy and diagnosis. Carbohydrates are natural, multifunctional, and stereochemically rich molecules, playing important roles in biological processes relevant for health and disease. Embodying such structural features, these unique molecular entities can be transformed in a diversity of compounds applied as drugs, food supplements, as biologically active materials, in cosmetics, just to name a few of the wide uses of carbohydrates and
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  • In the Search of Glycoside-Based Molecules As Antidiabetic Agents

    In the Search of Glycoside-Based Molecules As Antidiabetic Agents

    Topics in Current Chemistry (2019) 377:19 https://doi.org/10.1007/s41061-019-0243-6 REVIEW In the Search of Glycoside‑Based Molecules as Antidiabetic Agents Aleksandra Pałasz, et al. [full author details at the end of the article] Received: 20 December 2018 / Accepted: 14 May 2019 / Published online: 5 June 2019 © The Author(s) 2019 Abstract This review is an efort to summarize recent developments in synthesis of O-glyco- sides and N-, C-glycosyl molecules with promising antidiabetic potential. Articles published after 2000 are included. First, the O-glycosides used in the treatment of diabetes are presented, followed by the N-glycosides and fnally the C-glycosides constituting the largest group of antidiabetic drugs are described. Within each group of glycosides, we presented how the structure of compounds representing poten- tial drugs changes and when discussing chemical compounds of a similar structure, achievements are presented in the chronological order. C-Glycosyl compounds mim- icking O-glycosides structure, exhibit the best features in terms of pharmacody- namics and pharmacokinetics. Therefore, the largest part of the article is concerned with the description of the synthesis and biological studies of various C-glycosides. Also N-glycosides such as N-(β-D-glucopyranosyl)-amides, N-(β-D-glucopyranosyl)- ureas, and 1,2,3-triazolyl derivatives belong to the most potent classes of antidia- betic agents. In order to indicate which of the compounds presented in the given sec- tions have the best inhibitory properties, a list of the best inhibitors is presented at the end of each section. In summary, the best inhibitors were selected from each of the summarizing fgures and the results of the ranking were placed.