Printed Edition of the Special Issue Published in Molecules Phytoalexins: Current Progress and Future Prospects Edited by Philippe Jeandet www.mdpi.com/journal/molecules Philippe Jeandet (Ed.) Phytoalexins: Current Progress and Future Prospects This book is a reprint of the special issue that appeared in the online open access journal Molecules (ISSN 1420-3049) in 2014 (available at: http://www.mdpi.com/journal/molecules/special_issues/phytoalexins-progress). Guest Editor Philippe Jeandet Laboratory of Stress, Defenses and Plant Reproduction U.R.V.V.C., UPRES EA 4707, Faculty of Sciences, University of Reims, PO Box. 1039, 51687 Reims cedex 02, France Editorial Office MDPI AG Klybeckstrasse 64 Basel, Switzerland Publisher Shu-Kun Lin Managing Editor Ran Dang 1. Edition 2015 MDPI • Basel • Beijing • Wuhan ISBN 978-3-03842-058-3 (Hbk) ISBN 978-3-03842-059-0 (PDF) © 2015 by the authors; licensee MDPI, Basel, Switzerland. All articles in this volume are Open Access distributed under the Creative Commons License (CC BY), which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. However, the dissemination and distribution of copies of this book as a whole is restricted to MDPI, Basel, Switzerland. III Table of Contents About the Guest Editor ....................................................................................................... VII List of Contributors............................................................................................................VIII Editorial - Philippe Jeandet Phytoalexins: Current Progress and Future Prospects Reprinted from: Molecules 2015 , 20 , 2770-2774 http://www.mdpi.com/1420-3049/20/2/2770 .......................................................................... 1 Philippe Jeandet, Claire Hébrard, Marie-Alice Deville, Sylvain Cordelier, Stéphan Dorey, Aziz Aziz and Jérôme Crouzet Deciphering the Role of Phytoalexins in Plant-Microorganism Interactions and Human Health Reprinted from: Molecules 2014 , 19 , 18033 – 18056 http://www.mdpi.com/1420-3049/19/11/18033 ...................................................................... 6 Alana Poloni and Jan Schirawski Red Card for Pathogens: Phytoalexins in Sorghum and Maize Reprinted from: Molecules 2014 , 19 , 9114 – 9133 http://www.mdpi.com/1420-3049/19/7/9114 ........................................................................ 30 Yinning Chen, Tao Yan, Chenghai Gao, Wenhao Cao and Riming Huang Natural Products from the Genus Tephrosia Reprinted from: Molecules 2014 , 19 , 1432 – 1458 http://www.mdpi.com/1420-3049/19/2/1432 ........................................................................ 50 Magda Formela, Sławomir Samardakiewicz , Łukasz Marczak , Witold Nowak, Dorota Narożna , Waldemar Bednarski, Anna Kasprowicz- Maluśki and Iwona Morkunas Effects of Endogenous Signals and Fusarium oxysporum on the Mechanism Regulating Genistein Synthesis and Accumulation in Yellow Lupine and Their Impact on Plant Cell Cytoskeleton Reprinted from: Molecules 2014 , 19 , 13392 – 13421 http://www.mdpi.com/1420-3049/19/9/13392 ...................................................................... 77 IV Olga V. Zernova, Anatoli V. Lygin, Michelle L. Pawlowski, Curtis B. Hill, Glen L. Hartman, Jack M. Widholm and Vera V. Lozovaya Regulation of Plant Immunity through Modulation of Phytoalexin Synthesis Reprinted from: Molecules 2014 , 19 , 7480 – 7496 http://www.mdpi.com/1420-3049/19/6/7480 ...................................................................... 114 Farag Ibraheem, Iffa Gaffoor, Qixian Tan, Chi-Ren Shyu and Surinder Chopra A Sorghum MYB Transcription Factor Induces 3-Deoxyanthocyanidins and Enhances Resistance against Leaf Blights in Maize Reprinted from: Molecules 2015 , 20 , 2388 – 2404 http://www.mdpi.com/1420-3049/20/2/2388 ...................................................................... 131 Lee A. Hadwiger and Kiwamu Tanaka EDTA a Novel Inducer of Pisatin, a Phytoalexin Indicator of the Non-Host Resistance in Peas Reprinted from: Molecules 2015 , 20 , 24 – 34 http://www.mdpi.com/1420-3049/20/1/24 .......................................................................... 149 Simona M. Sanzani, Leonardo Schena and Antonio Ippolito Effectiveness of Phenolic Compounds against Citrus Green Mould Reprinted from: Molecules 2014 , 19 , 12500 – 12508 http://www.mdpi.com/1420-3049/19/8/12500 .................................................................... 160 Morifumi Hasegawa, Ichiro Mitsuhara, Shigemi Seo, Kazunori Okada, Hisakazu Yamane, Takayoshi Iwai and Yuko Ohashi Analysis on Blast Fungus-Responsive Characters of a Flavonoid Phytoalexin Sakuranetin; Accumulation in Infected Rice Leaves, Antifungal Activity and Detoxification by Fungus Reprinted from: Molecules 2014 , 19 , 11404 – 11418 http://www.mdpi.com/1420-3049/19/8/11404 .................................................................... 169 Malik Chalal, Agnès Klinguer, Abdelwahad Echairi, Philippe Meunier, Dominique Vervandier-Fasseur and Marielle Adrian Antimicrobial Activity of Resveratrol Analogues Reprinted from: Molecules 2014 , 19 , 7679 – 7688 http://www.mdpi.com/1420-3049/19/6/7679 ...................................................................... 184 V Yangrae Cho, Robin A. Ohm, Rakshit Devappa, Hyang Burm Lee, Igor V. Grigoriev, Bo Yeon Kim and Jong Seog Ahn Transcriptional Responses of the Bdtf1 -Deletion Mutant to the Phytoalexin Brassinin in the Necrotrophic Fungus Alternaria brassicicola Reprinted from: Molecules 2014 , 19 , 10717 – 10732 http://www.mdpi.com/1420-3049/19/8/10717 .................................................................... 193 Loïc Becker, Vincent Carré, Anne Poutaraud, Didier Merdinoglu and Patrick Chaimbault MALDI Mass Spectrometry Imaging for the Simultaneous Location of Resveratrol, Pterostilbene and Viniferins on Grapevine Leaves Reprinted from: Molecules 2014 , 19 , 10587 – 10600 http://www.mdpi.com/1420-3049/19/7/10587 .................................................................... 372 Guillaume Marti, Sylvain Schnee, Yannis Andrey, Claudia Simoes-Pires, Pierre-Alain Carrupt, Jean-Luc Wolfender and Katia Gindro Study of Leaf Metabolome Modifications Induced by UV-C Radiations in Representative Vitis , Cissus and Cannabis Species by LC-MS Based Metabolomics and Antioxidant Assays Reprinted from: Molecules 2014 , 19 , 14004 – 14021 http://www.mdpi.com/1420-3049/19/9/14004 .................................................................... 386 Glòria Lozano-Mena, Marta Sánchez-González, M. Emília Juan and Joana M. Planas Maslinic Acid, a Natural Phytoalexin-Type Triterpene from Olives — A Promising Nutraceutical? Reprinted from: Molecules 2014 , 19 , 11538 – 11559 http://www.mdpi.com/1420-3049/19/8/11538 .................................................................... 404 Martin Kello, David Drutovic, Martina Chripkova, Martina Pilatova, Mariana Budovska, Lucia Kulikova, Peter Urdzik and Jan Mojzis ROS-Dependent Antiproliferative Effect of Brassinin Derivative Homobrassinin in Human Colorectal Cancer Caco2 Cells Reprinted from: Molecules 2014 , 19 , 10877 – 10897 http://www.mdpi.com/1420-3049/19/8/10877 .................................................................... 426 VI Basil Smith, Diandra Randle, Roman Mezencev, LeeShawn Thomas, Cimona Hinton and Valerie Odero-Marah Camalexin-Induced Apoptosis in Prostate Cancer Cells Involves Alterations of Expression and Activity of Lysosomal Protease Cathepsin D Reprinted from: Molecules 2014 , 19 , 3988 – 4005 http://www.mdpi.com/1420-3049/19/4/3988 ...................................................................... 447 Audrey E. McCalley, Simon Kaja, Andrew J. Payne and Peter Koulen Resveratrol and Calcium Signaling: Molecular Mechanisms and Clinical Relevance Reprinted from: Molecules 2014 , 19 , 7327 – 7340 http://www.mdpi.com/1420-3049/19/6/7327 ...................................................................... 466 Malik Chalal, Dominique Delmas, Philippe Meunier, Norbert Latruffe and Dominique Vervandier-Fasseur Inhibition of Cancer Derived Cell Lines Proliferation by Synthesized Hydroxylated Stilbenes and New Ferrocenyl-Stilbene Analogs. Comparison with Resveratrol Reprinted from: Molecules 2014 , 19 , 7850 – 7868 http://www.mdpi.com/1420-3049/19/6/7850 ...................................................................... 480 VII About the Guest Editor Philippe Jeandet received his doctorates in plant physiology and biochemistry in 1991 and 1996 from the University of Bourgogne (France). He started his research activities on resveratrol, a phytoalexin from the Vitaceae produced in response to fungal attacks or injury. He received an associate professor position at the University of Bourgogne (1993-1997). In 1997, Philippe Jeandet accepted a position as a professor and chairman of the laboratory of oenology and applied chemistry at the University of Reims. His research activities focussed on physico-chemistry applied to wine and microbiology. He has been respectively the director (2003-2008) and adjunct director (2008-2013) of the research unit vine and wine of Champagne and adjunct to the director of research and technology in the Champagne- Ardennes area (2004-2010). He is now co-leader of a research team on resveratrol at the laboratory of stress, defences and plant reproduction and member of the council of the Georges Chappaz research institute of vine and wine of Champagne. He has published over 250 papers in referred Journals or books (with many of them concerning phytoalexins) as well as technical papers, edited two books and two special issues and presented 240 communications to numerous symposia or congresses. VIII List of Contributors Marielle Adrian: Université de Bourgogne, UMR1347 Agroécologie, ERL CNRS 6300, BP 86510, 21065 Dijon Cedex, France. Jong Seog Ahn: Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk 363-883, Korea. Yannis Andrey: School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, Geneva CH-1211, Switzerland. Aziz Aziz: Laboratory of Stress, Defenses and Plant Reproduction, Research Unit "Vines and Wines of Champagne", UPRES EA 4707, Department of Biology and Biochemistry, Faculty of Sciences, University of Reims, P.O. Box 1039, 51687 Reims cedex 02, France. Loïc Becker: Laboratoire de Chimie et Physique-Approche Multi échelle des Milieux Complexes (LCP-A2MC), Institut Jean Barriol (FR 2843), Université de Lorraine, ICPM 1 Boulevard Arago, F-57078 Metz, France. Waldemar Bednarski: Institute of Molecular Physics, Polish Academy of Sciences, Smoluchowskiego 17, Poznań 60 -179, Poland. Mariana Budovska: Department of Organic Chemistry, Institute of Chemical Sciences, Faculty of Science, Pavol Jozef Safarik University, 040 80 Kosice, Slovak Republic. Wenhao Cao: South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China. Vincent Carré: Laboratoire de Chimie et Physique-Approche Multi échelle des Milieux Complexes (LCP-A2MC), Institut Jean Barriol (FR 2843), Université de Lorraine, ICPM 1 Boulevard Arago, F-57078 Metz, France. Pierre-Alain Carrupt: School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, Geneva CH-1211, Switzerland. Patrick Chaimbault: Laboratoire de Chimie et Physique-Approche Multi échelle des Milieux Complexes (LCP-A2MC), Institut Jean Barriol (FR 2843), Université de Lorraine, ICPM 1 Boulevard Arago, F-57078 Metz, France. Malik Chalal: Université de Bourgogne, 21000 Dijon, France; Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, 9, avenue Alain Savary, 21000 Dijon, France. Yinning Chen: Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China. Yangrae Cho: Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk 363-883, Korea. IX Surinder Chopra: Department of Plant Science, The Pennsylvania State University, University Park, PA 16802, USA; Intercollege Graduate Degree Program in Plant Biology, Pennsylvania State University, University Park, PA 16802, USA. Martina Chripkova: Department of Pharmacology, Faculty of Medicine, Pavol Jozef Safarik University, 040 11 Kosice, Slovak Republic. Sylvain Cordelier: Laboratory of Stress, Defenses and Plant Reproduction, Research Unit "Vines and Wines of Champagne", UPRES EA 4707, Department of Biology and Biochemistry, Faculty of Sciences, University of Reims, P.O. Box 1039, 51687 Reims cedex 02, France. Jérôme Crouzet: Laboratory of Stress, Defenses and Plant Reproduction, Research Unit "Vines and Wines of Champagne", UPRES EA 4707, Department of Biology and Biochemistry, Faculty of Sciences, University of Reims, P.O. Box 1039, 51687 Reims cedex 02, France. Dominique Delmas: Université de Bourgogne, 21000 Dijon, France; Laboratoire de Biochimie (Bio-PeroxIL) INSERM IFR 100, 6, boulevard Gabriel, Dijon, France; INSERM UMR 866, 7, boulevard Jeanne d'Arc, 21000 Dijon, France. Rakshit Devappa: Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk 363-883, Korea. Marie-Alice Deville: Champagne Deville, 13 rue Carnot, Verzy 51380, France. Stéphan Dorey: Laboratory of Stress, Defenses and Plant Reproduction, Research Unit "Vines and Wines of Champagne", UPRES EA 4707, Department of Biology and Biochemistry, Faculty of Sciences, University of Reims, P.O. Box 1039, 51687 Reims cedex 02, France. David Drutovic: Department of Pharmacology, Faculty of Medicine, Pavol Jozef Safarik University, 040 11 Kosice, Slovak Republic. Abdelwahad Echairi: Welience, Maison Régionale de L'Innovation, 64 A rue de Sully, CS 77124, 21071 Dijon Cedex, France. Magda Formela: Department of Plant Physiology, Poznań University of Life Sciences, Wołyńska 35, Poznań 60 -637, Poland. Iffa Gaffoor: Department of Plant Science, The Pennsylvania State University, University Park, PA 16802, USA. Chenghai Gao: Guangxi Key Laboratory of Marine Environmental Science, Guangxi Academy of Sciences, Nanning 530007, China. Katia Gindro: Station de recherche Agroscope, Institut des Sciences en Production Végétale IPV, Route de Duiller 50, P.O. Box 1012, Nyon 1260, Switzerland. Igor V. Grigoriev: Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek 94598, CA, USA. Lee A. Hadwiger: Department of Plant Pathology, Washington State University, Pullman, WA 99164-6430, USA. X Glen L. Hartman: United States Department of Agriculture (USDA), Agricultural Research Service, University of Illinois, 1101 W. Peabody Drive, Urbana, IL 61801, USA. Morifumi Hasegawa: College of Agriculture, Ibaraki University, 3-21-1 Chuo, Ami, Ibaraki 300-0393, Japan. Claire Hébrard: Laboratory of Stress, Defenses and Plant Reproduction, Research Unit "Vines and Wines of Champagne", UPRES EA 4707, Department of Biology and Biochemistry, Faculty of Sciences, University of Reims, P.O. Box 1039, 51687 Reims cedex 02, France. Curtis B. Hill: Department of Crop Sciences, University of Illinois, 1201 W. Gregory Drive, Urbana, IL 61801, USA. Cimona Hinton: Center for Cancer Research and Therapeutic development, Department of Biological Sciences, Clark Atlanta University, Atlanta, GA 30314, USA. Riming Huang: Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China. Farag Ibraheem: Department of Plant Science, The Pennsylvania State University, University Park, PA 16802, USA; Intercollege Graduate Degree Program in Plant Biology, Pennsylvania State University, University Park, PA 16802, USA; Botany Department, Faculty of Science, Mansoura University, AlMansoura, 35516, Egypt. Antonio Ippolito: Dipartimento di Scienze del Suolo, della Pianta e degli Alimenti, Università degli Studi Aldo Moro, Via G. Amendola 165/A, Bari 70126, Italy. Takayoshi Iwai: School of Food, Agricultural and Environmental Sciences, Miyagi University, 2-2-1 Hatadate, Taihaku, Sendai, Miyagi 982-0215, Japan. Philippe Jeandet: Laboratory of Stress, Defenses and Plant Reproduction, Research Unit "Vines and Wines of Champagne", UPRES EA 4707, Department of Biology and Biochemistry, Faculty of Sciences, University of Reims, P.O. Box 1039, 51687 Reims cedex 02, France. M. Emília Juan: Departament de Fisiologia and Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), Universitat de Barcelona (UB), Av. Joan XXIII s/n, 08028 Barcelona, Spain. Simon Kaja: Vision Research Center, Department of Ophthalmology, School of Medicine, University of Missouri — Kansas City, 2411 Holmes St., Kansas City, MO 64108, USA. Anna Kasprowicz- Maluśki : Department of Molecular and Cellular Biology, Faculty of Biology, Adam Mickiewicz University, Umultowska 89, Poznań 60 -614, Poland. Martin Kello: Department of Pharmacology, Faculty of Medicine, Pavol Jozef Safarik University, 040 11 Kosice, Slovak Republic. Bo Yeon Kim: Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk 363-883, Korea. Agnès Klinguer: INRA, UMR1347 Agroécologie, ERL CNRS 6300, BP 86510, 21065 Dijon Cedex, France. XI Peter Koulen: Vision Research Center, Department of Ophthalmology, School of Medicine, University of Missouri — Kansas City, 2411 Holmes St., Kansas City, MO 64108, USA; Department of Basic Medical Science, School of Medicine, University of Missouri — Kansas City, 2411 Holmes St., Kansas City, MO 64108, USA. Lucia Kulikova: Department of Experimental Medicine, Faculty of Medicine, Pavol Jozef Safarik University, 040 11 Kosice, Slovak Republic. Norbert Latruffe: Université de Bourgogne, 21000 Dijon, France; Laboratoire de Biochimie (Bio-PeroxIL) INSERM IFR 100, 6, boulevard Gabriel, Dijon, France. Hyang Burm Lee: Division of Applied Bioscience and Biotechnology, College of Agriculture and Life Sciences, Chonnam National University, Buk-Gu, Gwangju 500-757, Korea Glòria Lozano-Mena: Departament de Fisiologia and Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), Universitat de Barcelona (UB), Av. Joan XXIII s/n, 08028 Barcelona, Spain. Vera V. Lozovaya: Department of Crop Sciences, University of Illinois, 1201 W. Gregory Drive, Urbana, IL 61801, USA. Anatoli V. Lygin: Department of Crop Sciences, University of Illinois, 1201 W. Gregory Drive, Urbana, IL 61801, USA. Łukasz Marczak : Institute of Bioorganic Chemistry, Polish Academy of Sciences, Z. Noskowskiego 12/14, Poznań 61 -704, Poland. Guillaume Marti: School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, Geneva CH-1211, Switzerland. Audrey E. McCalley: Vision Research Center, Department of Ophthalmology, School of Medicine, University of Missouri — Kansas City, 2411 Holmes St., Kansas City, MO 64108, USA. Didier Merdinoglu: Institut National de Recherche en Agronomie (INRA) – Santé de la Vigne et Qualité du Vin (UMR 1131), 28 rue de Herrlisheim, F-68021 Colmar, France Philippe Meunier: Université de Bourgogne, 21000 Dijon, France; Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, 9, avenue Alain Savary, 21000 Dijon, France. Roman Mezencev: Department of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA. Ichiro Mitsuhara: National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602, Japan. Jan Mojzis: Department of Pharmacology, Faculty of Medicine, Pavol Jozef Safarik University, 040 11 Kosice, Slovak Republic. Iwona Morkunas: Department of Plant Physiology, P oznań University of Life Sciences, Wołyńska 35, Poznań 60 -637, Poland. Dorota Narożna : Department of Biochemistry and Biotechnology, Poznań University of Life Sciences, Dojazd 11, Poznań 60-632, Poland. XII Witold Nowak: Laboratory of Molecular Biology Techniques, Faculty of Biology, Adam Mickiewicz University, Umultowska 89, Poznań 60 -614, Poland. Valerie Odero-Marah: Center for Cancer Research and Therapeutic development, Department of Biological Sciences, Clark Atlanta University, Atlanta, GA 30314, USA. Yuko Ohashi: National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602, Japan. Robin A. Ohm: Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek 94598, CA, USA. Kazunori Okada: Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. Michelle L. Pawlowski: Department of Crop Sciences, University of Illinois, 1201 W. Gregory Drive, Urbana, IL 61801, USA. Andrew J. Payne: Vision Research Center, Department of Ophthalmology, School of Medicine, University of Missouri — Kansas City, 2411 Holmes St., Kansas City, MO 64108, USA. Martina Pilatova: Department of Pharmacology, Faculty of Medicine, Pavol Jozef Safarik University, 040 11 Kosice, Slovak Republic. Joana M. Planas: Departament de Fisiologia and Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), Universitat de Barcelona (UB), Av. Joan XXIII s/n, 08028 Barcelona, Spain. Alana Poloni: Department of Microbial Genetics, Institute of Applied Microbiology, Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, Aachen 52074, Germany. Anne Poutaraud: Institut National de Recherche en Agronomie (INRA) – Santé de la Vigne et Qualité du Vin (UMR 1131), 28 rue de Herrlisheim, F-68021 Colmar, France. Diandra Randle: Center for Cancer Research and Therapeutic development, Department of Biological Sciences, Clark Atlanta University, Atlanta, GA 30314, USA. Sławomir Samardakiewicz : Laboratory of Electron and Confocal Microscopy, Faculty of Biology, Adam Mickiewicz University, Umultowska 89, Poznań 60 -614, Poland. Marta Sánchez-González: Departament de Fisiologia and Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), Universitat de Barcelona (UB), Av. Joan XXIII s/n, 08028 Barcelona, Spain. Simona M. Sanzani: Dipartimento di Scienze del Suolo, della Pianta e degli Alimenti, Università degli Studi Aldo Moro, Via G. Amendola 165/A, Bari 70126, Italy. Leonardo Schena: Dipartimento di Agraria, Università degli Studi Mediterranea, Località Feo di Vito, Reggio Calabria 89124, Italy. Jan Schirawski: Department of Microbial Genetics, Institute of Applied Microbiology, Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, Aachen 52074, Germany. XIII Sylvain Schnee: Station de recherche Agroscope, Institut des Sciences en Production Végétale IPV, Route de Duiller 50, P.O. Box 1012, Nyon 1260, Switzerland. Shigemi Seo: National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602, Japan. Chi-Ren Shyu: MU Informatics Institute, University of Missouri, Columbia, MO 65201, USA. Claudia Simoes-Pires: School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, Geneva CH-1211, Switzerland. Basil Smith: Center for Cancer Research and Therapeutic development, Department of Biological Sciences, Clark Atlanta University, Atlanta, GA 30314, USA. Qixian Tan: Department of Plant Science, The Pennsylvania State University, University Park, PA 16802, USA. Kiwamu Tanaka: Department of Plant Pathology, Washington State University, Pullman, WA 99164-6430, USA. LeeShawn Thomas: Department of Biological Sciences, Florida A & M University, Tallahassee, FL 32307, USA. Peter Urdzik: Department of Gynaecology and Obstetrics, Faculty of Medicine, Pavol Jozef Safarik University, 040 11 Kosice, Slovak Republic; Pasteur University Hospital, 040 11 Kosice, Slovak Republic. Dominique Vervandier-Fasseur: Université de Bourgogne, 21000 Dijon, France; Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, 9, avenue Alain Savary, 21000 Dijon, France. Jack M. Widholm: Department of Crop Sciences, University of Illinois, 1201 W. Gregory Drive, Urbana, IL 61801, USA. Jean-Luc Wolfender: School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, Geneva CH-1211, Switzerland. Hisakazu Yamane: Department of Biosciences, Teikyo University, 1-1 Toyosatodai, Utsunomiya, Tochigi 320-8551, Japan. Tao Yan: South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China. Olga V. Zernova: Department of Crop Sciences, University of Illinois, 1201 W. Gregory Drive, Urbana, IL 61801, USA. 1 Phytoalexins: Current Progress and Future Prospects Philippe Jeandet Reprinted from Molecules . Cite as: Jeandet, P Phytoalexins: Current Progress and Future Prospects Molecules 2015 , 20 , 2770-2774. Phytoalexins are low molecular weight antimicrobial compounds that are produced by plants as a response to biotic and abiotic stresses. As such they take part in an intricate defense system which enables plants to control invading microorganisms. In the 1950s, research on phytoalexins started with progress in their biochemistry and bio-organic chemistry, resulting in the determination of their structure, their biological activity, as well as mechanisms of their synthesis and catabolism by microorganisms. Elucidation of the biosynthesis of numerous phytoalexins also permitted the use of molecular biology tools for the exploration of the genes encoding enzymes of their synthesis pathways and their regulators. This has led to potential applications for increasing plant resistance to diseases. Phytoalexins display an enormous diversity belonging to various chemical families such as for instance, phenolics, terpenoids, furanoacetylenes, steroid glycoalkaloids, sulfur-containing compounds and indoles. Research and review papers dealing with numerous aspects of phytoalexins including modulation of their biosynthesis, molecular engineering in plants, biological activities, structure/activity relationships and phytoalexin metabolism by micro-organisms are published in this issue. In the first paper of this special issue on phytoalexins, Jeandet et al. present an overview of this diverse group of molecules, namely their chemical diversity, the main biosynthetic pathways and their regulatory mechanisms, fungal metabolism, phytoalexin gene transfer in plants and their role as antifungal and bactericidal agents as well as their involvement in human health [1]. General aspects of phytoalexins from the Leguminosae and Poaceae families are also discussed in this issue. Phytoalexins from sorghum and maize are presented in details by Poloni and Schirawski [2]. Sorghum produces two distinct phytoalexins belonging to the 3-deoxyanthocyanidin chemical group, apigeninidin and luteolinidin. Their biosynthetic pathways start from the flavanone naringenin according to a scheme slightly different from that of the anthocyanin route. In maize, phytoalexins are represented by members of the terpenoid class, including zealexins and kauralexins on the one hand and benzoxazinoids on the other hand, the biosynthesis of which are fully described. Biosynthesis aspects have been linked to both the elicitation and the up-regulation mechanisms of those phytoalexins. Various applications of sorghum and maize phytoalexins in plant disease resistance and health and biomedicine are also presented. Within the Leguminosae family, the genus Tephrosia , a large pantropical genus composed of more than 350 species, is a source of numerous chemical constituents possessing various biological properties, including phytoalexin-like compounds. These compounds which are reviewed in this issue by Chen et al. , are mainly polyphenolics (flavones, flavonols, flavononols, flavans, isoflavones and chalcones), triterpenoids and sesquiterpenes [3]. Biosynthetic pathways of a number of these compounds are described as well as some of their biological activities as estrogenic, antitumor, antimicrobial, antiprotozoal and antifeedant agents. 2 Elucidating the molecular mechanisms of the modulation of phytoalexin biosynthesis finds applications in plant engineering for disease resistance. In this issue, Formela et al. report the effects of various sugars (sucrose, glucose and fructose) acting as endogenous signals on the mechanisms regulating the biosynthesis and accumulation of the lupine phytoalexin, genistein as well as the expression of other isoflavonoid biosynthetic genes [4]. Zernova et al. describe the transformation of soybean hairy roots with both the peanut resveratrol synthase 3 AhRS3 gene and the resveratrol- O -methyltransferase ROMT gene [5]. Overexpression of these two genes resulted in the production of resveratrol and its methylated derivative pterostilbene and a lower necrosis of the transformed tissues (only 0 to 7%) in response to the soybean pathogen Rhizoctonia solani compared to the wild-type ones which exhibited about 84% necrosis. Biosynthesis of the 3-deoxyanthocyanidin phytoalexins from sorghum is reported in transgenic maize lines expressing the MYB transcription factor yellow seed1 ( y1 ), an orthologue of the maize gene pericarp color1 ( p1 ) in the work of Ibraheem et al. [6]. Expression of this transcription factor leads to the production of chemically modified 3-deoxyanthocyanidins and a resistance response of Y1 -maize plants to leaf blight ( Colletotrichum graminicola ). It is well known that treatment of plants with various biotic or abiotic agents, the so-called elicitors, can activate complex mechanisms in the cells by altering primary and secondary metabolisms in a coordinate fashion. Elicitors are also recognized as efficient inducers of phytoalexins. In this issue, Hadwiger and Tanaka report that EDTA, used at low concentrations, is a new elicitor of pisatin, a phytoalexin indicator of non-host resistance in pea [7]. Eliciting activity of EDTA seems to be linked to induction of cell DNA damage and defense-responsive genes. The question of the function of phytoalexins as true antifungal agents still remains unanswered. Interestingly, a study of Sanzani et al. underline the effectiveness both in vitro and in vivo of some polyphenolic phytoalexins, namely the coumarin, scopoletin, on the reduction of green mold symptoms caused by Penicillium digitatum on oranges by 40 to 85% [8]. Based on these results, the authors conclude that treatment of plants with phytoalexins may represent an interesting alternative to synthetic fungicides. In another work by Hasegawa et al. , the activity of two rice phytoalexins, sakuranetin and momilactone A was tested in vitro and in vivo on the blast fungus Magnaporthe oryzae Sakuranetin exhibits a higher antifungal activity than does momilactone A, respectively 40%–55% and 12%–17% reduction of mycelial growth [9]. To increase the fungitoxicity of phytoalexins, design and synthesis of more active phytoalexin derivatives is needed. Chalal et al. report in this issue the synthesis of a series of 13 trans -resveratrol analogues via Wittig or Heck reactions and assess their antimicrobial activity on two different grapevine pathogens, Plasmopara viticola and Botrytis cinerea [10]. Stilbenes displayed a spectrum of activity ranging from low to high, suggesting a relationship between the chemical structures of the synthesized stilbenes (number and position of methoxy and hydroxyphenyl groups) and their antimicrobial activity. The ability of a fungal pathogen to weaken or neutralize the toxic effects of phytoalexins is one of the essential parameters determining the outcome of the interaction between this pathogen and its host plant. The necrotrophic fungus Alternaria brassicicola is known to detoxify brassinin, the indolic phytoalexin from the Brassicaceae family. A transcription factor Bdtf1 is essential for 3 brassinin detoxification and fungal host range. In this issue, Cho et al. show that beside this transcriptional factor, 10 putative genes were assumed to be involved in the detoxification of brassinin using a Bdtf1 -deletion mutant of the necrotrophic fungus A. brassicicola [11]. Another limitation in our knowledge of phytoalexins is the difficulty in analyzing the events occurring between the plant and the pathogen under natural conditions. Some attempts to determine the actual concentrations and the nature of phytoalexins directly in plant tissues in response to invading microorganisms have been carried out using spectroscopic methods. Becker et al. in this issue describe mass spectrometry (ESI-FTIR-RMS) and imaging mass spectrometry techniques to evaluate the response of grapevine leaves to P. viticola , the causal agent of downy mildew [12]. Most importantly, molecular mapping of grapevine leaves by laser desorption/ionization mass spectrometry reveals a specific spatial distribution of some stilbene phytoalexins produced upon the infection process. To assess modifications of the phytoalexin metabolism in planta , global and untargeted approaches are also needed. Here, Marti et al. use a Liquid Chromatography-High Resolution Mass Spectrometry-based metabolomic approach to evaluate stilbene phytoalexin modifications as a response to an abiotic stress (UV-C radiations) in leaves of three different model plant species, Cissus Antarctica Vent (Vitaceae), Vitis vinifera L. (Vitaceae) and Cannabis sativa L. (Cannabaceae) [13]. Interestingly, phytoalexins have found many applications in human health and disease. For example, Lozano-Mena et al. review in this issue the role of maslinic acid, a pentacyclic triterpene phytoalexin-like compound present in various natural sources such as herbal remedies as well as edible vegetables and fruits, as an antitumor, antidiabetic, antioxidant, cardioprotective, neuroprotective, antiparasitic and growth-stimulating agent both in experimental and animal models [14]. This offers perspectives for this compound to be used as a nutraceutical. Moreover, other phytoalexins such as brassinin and its derivative, homobrassinin, show marked antiproliferative activities in vitro . In this issue, Kello et al. indeed report that the inhibitory effects of the phytoalexin homobrassinin in human colorectal cancer cells is associated with apoptosis, G2/M phase arrest, deregulation of tubulin expression together with the loss of mitochondrial membrane potential, caspase-3 activation and intracellular reactive oxygen species production [15]. Smith et al. also demonstrate that the indolic phytoalexin, camalexin, exerts antitumor activity against prostate cancer cell lines by alterations of expression and activity of a lysosomal protease, cathepsin D [16]. Immunochemical analysis reveals cathepsin D relocalization from the lysosome to the cytoplasm according to camalexin treatment which is responsible for apoptosis in those cells. One of the most promising molecules in terms of biological benefits for humans, the resveratrol, is reviewed by McCalley et al. regarding its effects on intracellular calcium signaling mechanisms [17]. Resveratrol’s mechanisms of action are likely to be pleitropic and mediated by the interaction of this compound with key signaling proteins controlling cellular calcium homeostasis. The clinical relevance of resveratrol actions on excitable cells, transformed or cancer cells and immune cells was put in parallel with the molecular mechanisms affecting intra cellular calcium signaling proteins. Lack of efficacy of some natural phytoalexins in reducing tumors has led to a number of investigations regarding the design and synthesis of more potent anticancer derivatives of known phytoalexins. Chalal et al. in this issue describe the synthesis of hydroxylated and methylated 4 resveratrol derivatives using Wittig and Heck reactions as well as of ferrocenyl-stilbene analogs, with potent anticancer activities on human colorectal tumor SW480 cell lines [18]. However, weaker effects of the synthesized resveratrol derivatives were observed on the human hepatoblastoma HepG2 cells, showing the selectivity of those compounds for cancer treatment. All the papers presented in this special issue thus underline the central role of phytoalexins in plant diseases as well as their involvement in human health and disease. 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