BIOACTIVE NATUR AL PRODUCTS Opportunities and Challenges in Medicinal Chemistry 8033hc.9789814335379-tp.indd 8/29/11 10:32 AM BIOACTIVE NATURAL PRODUCTS Opportunities and Challenges in Medicinal Chemistry editor Goutam Brahmachari Visva-Bharati University, India World Scientific NEW JERSEY • LONDON 8033hc.9789814335379-tp.indd • SINGAPORE • BEIJING • SHANGHAI • HONG KONG • TA I P E I • CHENNAI 8/29/11 10:32 AM Published by World Scientific Publishing Co Pte Ltd Toh Tuck Link, Singapore 596224 USA office: 27 Warren Street, Suite 401-402, Hackensack, NJ 07601 UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library BIOACTIVE NATURAL PRODUCTS Opportunities and Challenges in Medicinal Chemistry Copyright © 2012 by World Scientific Publishing Co Pte Ltd All rights reserved This book, or parts thereof, may not be reproduced in any form or by any means, electronic or mechanical, including photocopying, recording or any information storage and retrieval system now known or to be invented, without written permission from the Publisher For photocopying of material in this volume, please pay a copying fee through the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA In this case permission to photocopy is not required from the publisher ISBN-13 978-981-4335-37-9 ISBN-10 981-4335-37-1 Typeset by Stallion Press Email: enquiries@stallionpress.com Printed in Singapore Jihan - Bioactive Natural Products.pmd 10/14/2011, 9:09 AM b1214_FM.qxd 8/24/2011 5:41 PM Page v b1214 Bioactive Natural Products To All those who are working globally with bioactive natural products for the cause of human welfare b1214_FM.qxd 8/24/2011 5:41 PM Page vii b1214 Bioactive Natural Products Foreword Unlike other books with a similar title, this edited volume covers not only secondary metabolites from natural product sources and their derivatives, but also a significant amount of what might best be covered under the rubric of alternative medicine or even functional food stuffs In addition, it also contains excellent chapters on the methodologies of production of “natural products that will be drug molecules in their own right” Thus there are chapters by well-known experts on not only classical fermentation processes using microbes, but also on the methodologies involved in plant tissue culture This latter system is one that is not often referred to for drug production, but over the last 5+ years, it has become a major method for the production of the antitumor drug Taxol® by BristolMyers Squibb A point that is often forgotten in westernized medicine is that of the approximate billion people in the world at this moment, more than 80% of them not have routine access to drugs as they are defined in Western medicine, but rely upon predominately plant-based therapies as their sources of medicinal agents Even in areas of the world where single agent drugs are available, traditional therapeutic regimens such as Ayurveda in India, Traditional Chinese Medicine, and Japanese and Korean herbals are still the major source of medicinals Thus in this volume, as a result of a careful juxtaposition of what might be called “classical natural product-based drug discovery” where pure single compounds or their close chemical relatives, are used as ethical pharmaceutical agents, with commentaries on the history and use of agents found in “functional foods and alternative therapies”, the reader will have a more nuanced understanding of the role that natural vii b1214_FM.qxd 8/24/2011 5:41 PM Page viii b1214 Bioactive Natural Products viii Foreword products, in the widest sense of the term, has had upon the discovery and development of agents — be they single agents, or validated mixtures, that can be utilized to maintain the health of people from all areas of the world David J Newman Wayne, Pennsylvania, USA June, 2011 b1214_FM.qxd 8/24/2011 5:41 PM Page ix b1214 Bioactive Natural Products Preface This single volume entitled Bioactive Natural Products: Opportunities & Challenges in Medicinal Chemistry is an endeavor to underline how natural product research continues to make significant contributions in the domain of discovery and development of new medicinal entities; the present book brings together a total of fourteen articles contributed by eminent natural product chemists from several countries in response to my personal invitation I am most grateful to the authors for their generous and timely response in spite of their busy and tight schedules with academics, research, and other responsibilities Nature stands as an inexhaustible source of novel chemotypes and pharmacophores; natural products present in the plant and animal kingdom offer a large diversity of chemical structures which are the result of biosynthetic processes that have been modulated over the millennia through genetic effects Interest in obtaining biologically active compounds from natural sources has recently spiked due to their low toxicity, availability from renewable sources, complete biodegradability, and in most cases, low cost as well Bioactive natural products are proving to be a rich source of novel therapeutics The search for bioactive molecules from nature (plants, animals, microflora) continues to play an important role in fashioning new medicinal agents With the advent of modern techniques, particularly the rapid improvements in spectroscopic as well as accompanying advances in high-throughput screening techniques, it has become possible to have an enormous repository of bioactive natural compounds, thus opening up exciting new opportunities in the field of new drug development to the pharmaceutical industry Medicinal chemistry of bioactive natural products spans a wide range of fields, including isolation and characterization of bioactive compounds from natural sources, structure modification for optimization of their ix b1214_Index.qxd 8/24/2011 12:53 PM Page 656 b1214 Bioactive Natural Products 656 Index Allelopathy 637 Aloe barbadensis 541 Aloe vera 509 Aloin 509 α-1,3-Fucosyltransferase 644 α1-Adrenoceptor (AR) 339 α-Glucosidase 521, 525, 551, 564 Alyssum 483 Alzheimer’s disease (AD) 369 Amentoflavone 465 Amino acid 406, 610 Amodiaquine 226, 227, 257 Amorpha-4,11-diene 247, 249 Synthase 247 Amorphadiene 247 Synthase 249 Amrubicin hydrochloride 39 Anabaseine 84 Anacardic acid 487 Andrographis paniculata 335 Andrographolide 335, 336 Anemia 246 Angelica keiskei 564 Angelica dahurica 642 Angiotensin I-converting enzyme 202 Angusticornin B 447 Angylocalyx pynaertii 526 Anidulafungin 35 Anthemis altissima L 479 Anthocyanin 461 Anthrax 644 Anti-angiogenic 322 Anti-atherosclerotic 214 Antibiotic resistance 475 Anticancer 254, 639, 642, 643, 645 Antifugal 254 Anti-HIV 643 Anti-inflammatory 410, 640, 642, 643 Antileishmaniasis 254 Antimalarial 311, 313, 314, 328, 633, 645 Aurantio-obtusin 575 Antioxidative functions 412 Antioxoplasmosis 254 Antirheumatic 642 Antishistosomiasis 254 Antitrypanosomiasis 254 Antitumor 642 Antiulcer 314 Antiviral 254 Apicidin 283–285, 287, 297 Apigenin 552 Arabidopsis thaliana 636, 637 Arachidonic acid 409 Areca catechu 373 Arecoline 373 Argyreia speciosa 448 Arteannuin B 312, 313 Arteether 18, 243 Artelinate 243 Artemether 243, 321, 327 Artemisia annua 18, 223, 225, 242, 247, 249, 251, 260, 633 Artemisia douglasiana 480 Artemisia ketone 312, 313 Artemisinin 62, 223, 225, 239, 242, 247, 249, 254, 260, 633, 640, 641, 645; see also Deoxyartemisinin, Dihydroartemisinin Artemisinic acid 249 Artemisinic alcohol 248, 312, 313 b1214_Index.qxd 8/24/2011 12:53 PM Page 657 b1214 Bioactive Natural Products Index Artemisinic aldehyde 248 Artemisinin-containing treatment (ACTs) 228, 244 Artemisinin–fullerene 327 Artemisinin–quinine hybrid 242 Biosynthesis 247, 248 11-Hydroxy-11-epi-artemisinin 321 11-Hydroxyartemisinin 321 Tetrameric artemisinin derivatives 251, 254 Total synthesis 250 Toxicity 246 ArtequinTM 244 Artesunate 243, 321, 327 Arthemether 246 Artichoke powder 404 Ascorbic acid 404 Aspergillus fumigatus 34 Aspirin 7, 372 Astianthus viminalis 547 Astilbin 556 Astragalus membranaceus 456, 543 Angiotensin II type-1 receptor (AT1-R) 202 Atebrine 226 Atherosclerotic 215 Atovaquone 254 Atropa belladonna 54, 641 Axinella cannabina 258 Axisonitrile-3 258 Azadirachthin 507 Aztreonam lysine 38 Azumamide 279, 280 657 B Baccatin III 635, 639 BACE1 381 Baicalein 448, 551 BALB/c mice 644 Banana 643 Bartericin A 447 Bauhinia forficata 558 Bauhinia megalandra 554 Bauhinia purpurea 457 Beauveria sp 384 Beilschmiedia zenkeri 457 Bellidifolin 574 Berberine 506, 528, 637, 638, 642, 643 Berteroa incana 483 β-1,2-Xylosyltransferase 644 β-Endorphin-like immunoreactivity (BER) 339 β-Hematin 227 β-Lapachone 69 Betulinic acid 62 Biapenem 29 Bidens pilosa 578 Biflavanoid 415, 445, 464 Bioflavonoid 549; see also Flavonoid Biologically active supplement (BAS) 403 Biopharmaceuticals 618–621 Bispyridinium diene 281 Bivalirudin 55 Blood-stage gametocyte 243 Boesenbergia pandurata 461 Botanical 475 Bovine viral diarrhea 314 b1214_Index.qxd 8/24/2011 12:53 PM Page 658 b1214 Bioactive Natural Products 658 Index Brain-derived neurotrophic factor 388 Brassica oleracea 483 Bronchopneumonia 428, 429, 431 Brucea javanica 578 Bruceine 578 Bryostatin 85 Butein 566 Butyrate 275, 276, 284 C C57BL/6 mice 644 Caesalpinia brevifolia 565 Caffeic acid 570 Calicheamicin 39 Callistemon citrinus 58 Camphor 312, 313 Campthoteca acuminata 645 Camptothecin 66, 641, 642 Cancer therapy 312 Cannabidol 49 Capsaicin 52, 64 Carbapenem 71 Carboxydipeptidase 202 Cardaria draba 483 Cardiac arrhythmia 228 Carotenoid 418, 489 Carrot 643 Carum carvi 478 Casearia esculenta 577 Caspase 344 Caspofungin acetate 26 Cassia tora 575 Castanospermine 62, 524 Castanospermum australe 524 Casuarine 6-O-α-glucoside 527 Catalase (CAT) 338 Catechin 462 Catharanthine 638 Catharanthus roseus 634, 637, 638, 645 Cecropia obtusifolia 554 Cedrus libani 478 Cefditoren pivoxil 27 Cell suspension 631, 638, 640 Cells proliferation 312, 322, 323 Centaurea solstitialis 478 Cephalosporin 71 cGMP 205 Chalcone 254, 459 Cheiranthus cheiri 483 Chemical space 10 Chiral 321 Chlamydocin 285–287, 289 Chloroeremomycin 72 Chlorogenic acid 570 Chloroquine 226, 227, 239, 257 Resistance 241, 255, 258 Chloroquine-sensitive 258 Chloroquine-susceptible 255 Chromobacterium violaceum 45 Chronic diarrhea 477 Chronic obstructive pulmonary disease (COPD) 292, 294, 297 Chrysanthemum indicum 552 Cinchona 225, 226, 232 Cinchonism 228 Cinnamaldehyde 577 Cinnamomum zeylanicum 577 Cistus laurifolius 478, 482 Citicoline 389 Citrus aurantium 572 b1214_Index.qxd 8/24/2011 12:53 PM Page 659 b1214 Bioactive Natural Products Index Clarithromycin 477 Coartem™ 244 Coenzyme Q10 385 Cognition enhancement 374 Coleonol 11 Combretastatin A-1 67 Combretastatin A-4 66 Coptis japonica 529, 637, 643 Corn 644 Cornus officinalis 537, 570 Corosolic acid 547 Costunolide 536 Costus speciosus 536 Cotton 640 Coutareagenin 558 Cryptotanshinone 640, 641 Curcuma amada 482 Curcuma longa 381, 485, 509 Curcumin 68, 294, 295, 381, 382, 485, 510 Cuscuta reflexa 569 Cutaneous T-cell lymphoma (CTCL) 273, 275, 297 Cyanobacteria 225 Cycleanine 535 Cyclic adenosine monophosphate (cAMP) 205 Cyclooxygenase (COX) 205 Cyclosporin 77 Cyclosporin A 78 Cyclotide 642 Cymbastela hooperi 258 Cytochrome P450 monooxygenase 249 Cytochrome P450-dependent monooxygenase 247 Cytopiloyne 577 Cytosine 659 374 D DAB 526 Dacarbazine 327 Daidzein 69, 553 Danshenol A 539 Daptomycin 30 D-chiro-inositol 577 Death receptor (DR-4) 344 Decursinol 383 Dehydroleucodine 480 Dehydrotrametenolic acid 544 Dementia 369 Deoxyartemisinin 315 Deoxypodophyllotoxin 642 Depsipeptide 258, 384 Dermatology 313 Desmanthin-1 563 Diabetes Mellitus 520 Type 521 Type 522, 580 Diallyl disulfide 275–277, 297 Diazepinomicin 82 Digitoxin Digoxin 640 Dihydroartemisinin 243, 321, 327 Dihydroartemisinic aldehyde 248 Dihydroartemisinic acid 249, 315 Hydroperoxide 248 Diode array (DAD) 314, 315 Dioscorea sp 640 Diosgenin 640, 641 Distamycin A 80 b1214_Index.qxd 8/24/2011 12:53 PM Page 660 b1214 Bioactive Natural Products 660 Index Diversity-oriented synthesis (DOS) Docosahexaenoic acid 388 Dolastatin 10 85 Dolastatin 15 85 Donepezil 375 Doripenem 32 Dorsilurins F-K 558 Dorstenia angusticornis 447 Dorstenia psilurus 558 Doxorubicin 79, 323 Doxycycline 255 Dracaena cochinchinensis 481 Dronabinol 49 Drug discovery Drug-resistant parasite 225 Duodenal ulcer disease 476 Duramycin 74 E Eclipta alba 507 Ecteinascidia turbinate 42 Eczema 502 Endothelium-derived hyperpolarizing factor (EDHF) 205 Elephantopus scaber 543 Elettaria cardamomum 478 Ellipticine 323, 325 Elsamicin A 79 E-Mal 26 Emodin 575 Engeletin 556 Eosinophilia 246 Epigallocatechin 463 Epigallocatechin gallate 463 Epigenetics 273, 274 Epipodophyllotoxin 70 Epiquinine 233 Epothilone B 82 Epothilone D 83 Epoxyeicosatrienoic acid 206 Erigeroflavanone 562 Erigeron annuus 562 Eriobotrya japonica 540 Eriosema glomerata 460 Ertapenem 27 Eruca sativa 483 Eryhthrina latissima 454 Erylatissin C 456 Erythrina abyssinica 560 Erythrina burttii 454 Erythrina costaricensis 454 Erythrina crista galli 453 Erythromycin 74 Escherichia coli 644 Ethnomedicinal 477 Ethoxyresorufin-O-deethylation activity 338 Eucommia ulmoides 556 Eugenia caryophyllata 569 Eugenia jambolana 527 Eugeniin 569 Eupatilin 65 Euphorbia leucophylla 563 European Medicines Agency (EMEA) 17 Evaporative light scattering detector (ELSD) 314, 315 Everolimus 44 Evodia rutaecarpa 487, 524 Exenatide 57 Exogenous iron(II) 245 b1214_Index.qxd 8/24/2011 12:53 PM Page 661 b1214 Bioactive Natural Products Index F Factory development 615–618 Fangchinoline 534 Farnesyl diphosphate (FDP) 247 Fatty acid 409 Fermentation product market 617 Feroheam 245 Ferroquine 227 Ferula mongolica 540 Ficus chlamydocarpa 453 Ficus cordata 453 FK228 290; see also Romidepsin Flavanone 445, 456 Flavivirus 314 Flavone 275, 277 Flavonoid 313 Derivative 481 Glycoflavonoid 446 Isoflavonoid 452 Foeniculum vulgare 478 Foreign protein 633, 645 Formal synthesis of quinine 235 Forskolin 11 Fotemustine 327 FR235222 287 FR901228 290 Friulimicin B 73 Fumagillin 34 Fungi 225 Fungicidal 313 Furans 491 G Galangin 450 Galantamine 375 Galantamine hydrobromide 46 661 Galanthus nivalis 46, 375 Galega officinalis 522 γ-Glutamyl transpeptidase (γ-GTP) 338 γ-Linolenic acid 512 Gancaonin G 455 Gancaonin Q 447 Garcinia livingstonei 466 Garlic 492 Gas chromatography (GC) 314 Gastric B-cell lymphoma 476 Gastric carcinoma 476 Gastritis 476 Geldanamycin 80 Gemtuzumab ozogamicin 39 Gene silencing 635 Genistein 69, 454, 554 Gentiana lutea 478 Geranylgeranyl diphosphate (GGPP) 633, 635 Gibberellin 634 Gingerols 485 Gingko biloba 372, 379 Ginkgo Evaluation of Memory Study (GEMS) 380 Ginkgolides 379 Glandular trichome 633, 638, 639 Glarea lozoyensis 26 Global health hazard 475 Glucocorticoid-inducible system (alc-GR) 637 Glutamic-pyruvate transaminase (GPT) 338 Glutathione (GSH) 337 Peroxidase (GSH-Px) 338 Reductase 338 b1214_Index.qxd 8/24/2011 12:53 PM Page 662 b1214 Bioactive Natural Products 662 Index Glutathione-S-transferase (GST) 338 Gram-negative 476 Green tea 492 Grin Mix 404 Grin Pro 404 Grinization 401, 405, 407 Growth factor (GF) 346 Guaijaverin 563 Guanylyl cyclase (sGC) 206 Gynostemma pentaphyllum 544 H Heme oxygenase 228 Hemoglobin proteolysis 227 Hemozoin 227, 228 Halichondrin B 84 Harmaline 641, 642 Harmine 641, 642 HC toxin 288 Heme-based mechanism 246 Hedera helix 506 Helical-shaped 476 Helichrysum aureonitens 450 Helichrysum gymnocomum 461 Helicobacter pylori 448, 475, 476 Helminthosporium carbonum 287, 298 Hemiasterlin 84 Hemorrhagic pneumonia 430 Hepatitis 314, 416 Hepatitis C virus 452 Herbacetin 451 Herpes simplex 314 Hesperidin 553 Hesperitin 459 Heterothalamus alienus 458 Hexachlorocyclohexane (BHC) 338 High-performance liquid chromatography (HPLC) 314, 315 High-throughput screening (HTS) 14 Himbacine 65 Hintonia latiflora 558 Hirudin 644, 645 Homofascaplysin 260 Homoharringtonine 70 Homomeroquinene (3-vinyl-4piperidinepropionic acid) 233, 235 Synthesis 234 HRW 211 Human cytomegalovirus 314, 452 Human immunodeficiency virus (HIV) 346 Type (HIV-1) 642, 643 Human lymphoma cell line HeLa 642 Human serum albumin 644 Human umbilical vein endothelial (HUVEC) 322, 346 Human vascular endothelial growth factor (VEGF) 644 Huperzia serrata 376 Huperzine A 63, 376 Hydrastis canadiensis 487, 506 Hyoscianine 6β-hydroxilase 641 Hyperemesis gravidarum 476 Hypericum connatum 451 Hyrtios erecta 260 Hyssopus officinalis 564 b1214_Index.qxd 8/24/2011 12:53 PM Page 663 b1214 Bioactive Natural Products Index I Ilex litseaefolia 568 Illudin S 83 Immunoglobulin A (IgA) 644 G type (IgG1) 644 G type (IgG4) 644 Impaired growth 477 Impatiens balsamina 489 Imperatorin 641, 642 Indolicidin 87 Inducible nitric oxide synthase (iNOS) 341 Inflammation 476 Influenza 421, 424 A H1N1 virus 458 virus 437 Ingenol 70 Invanz™ 27 Iodine 413 Ischemic heart disease 476 Isoaffineyin 552 Isobavachalcone 460 Isocryptomerin 465 Isocycloamphilectane 258 Isonitrile kalihinanes 258 Isonymphaeol D 457 Isoorientin 554 Isotaxiresinol 572 Isothiocyanates 482 Ixabepilone 43 J Jasmonate 639, 640 Jonathan Vennerstrom 251 Jorumycin 85 Juniper communis 663 478 K Kaempferia parviflora 452 Kaempferitrin 558 Kaempferol-3-neohesperidoside 558 Kahalalide F 85 Kalata B1 642 Kalihinol A 258 Kan Jang 349 Kanzonol C 460 Kindler 233 Kinetin 509 Kotalanol 579 L Labile enterotoxin B (LT-B) 644 Laboratory improvement 607–609 Lactucain C 542 Lagerstroemia speciosa 547 Lapinone 254 Largazole 288, 289 Larrea divaricata 449 Lateral sclerosis (ALS) 383 Lavandula angustifolia 478 Lepidium sativum 483 Leprosy 507 Lettuce 643 Licochalcone A 255 Licorice (Glycyrrhiza glabra) 512 Linoleic acid 409 Linum flavum 642 Lisdexamphetamine 50 b1214_Index.qxd 8/24/2011 12:53 PM Page 664 b1214 Bioactive Natural Products 664 Index Lithospermum erythrorhizon Litseaefoloside C 568 Lobelia chinensis 527 Lobelia inflate 374 Lobeline 63, 374 L-sulforaphane 483 Lumefantrine 244 Lupanine 530 Lupinus perennis 530 Luteoforol 451 Luteolin 552, 563 Lymphoid infiltration 433 642 M Madagascar periwinkle 644 Magnesium 412 Mahanimbine 531, 532 Maize 643, 644 Malagasy medicinal plants 478 Malaria 640, 644 Malaria parasite’s genome 225 Malarone 254 Mallotus phillipinesis 482 Malnutrition 477 Malus domestica 489, 490 Mammalian target of rapamycin 44 Mammalian α-mannosidase 525 Manganese 412 Mangiferin 572 Manikara indica 552 Manzanine A 258 Mass spectrometry (MS) 314 Medicago 645 Mefloquine 226, 227, 244 Melissa officinalis 478 Memory enhancers 372 Mentha piperita 478 Mepacrine 226 Metabolic engineering 631, 632, 634, 645 Metabolic reprogramming 634 Metaquine 227 Methyl jasmonate 632, 640 Methylnaltrexone 51 Metronidazole 477 Met-Tyr (MY) 206 Mevalonate pathway 247, 249 Micafungin 33 Microbes 605, 606 Microwave-assisted extraction (MAE) 317, 318 Miglustat 59 Minocycline 255 Mitomycin 325 Molecular pharming 643 Momordica charantia 478 Mongolian gerbil 491 Monoclonal antibody 620, 621 Morphine 7, 63, 372 Morus alba 525 Morus bombycis 567 Mucuna pruriens 577 Multidrug-resistant 255, 257 Multi-nutrient functional complex 409 Murraya koenigii 531 Mutagenesis 610–612 Mutant 645 Mycoleptodonoides aitchisonii 203 Mycophenolate sodium 60 Myrcia multiflora 550 Myrciaria dubia 566 Myricetin 554 Myristica fragrans 478 b1214_Index.qxd 8/24/2011 12:53 PM Page 665 b1214 Bioactive Natural Products Index N Naphthoquinone 254 Naringin 553 Nasturnium officinale 483 Naturally occurring compound 475 Neem (Azadirachtha indica) 507 Nerve growth factor (NGF) 374 Neurodegeneration 371 Neutropenia 246 New Drug Application (NDA) 17 N-formyl-methinoyl-leucylphenylalanine (fMLP) 341 NF-κB 340, 341 N-glycosylation 644 Nicotiana plumbaginifolia 638 Nicotine 373, 637 Nitisinone 58 Nonmevalonate pathway 247 Nonsubstitutional amino acids (NSA) 403 Noscapine 68 Nostocarboline 258 Nothapodytes foetida 642 Novel genetic techniques 614, 615 NPI-2350 83 NSC-630176 290 Nuphar japonicum 565 O Obtusifolin 575 Oldenlandia affinis 642 Olea europeaea 548 Oleanolic acid 68 Omega-3 fatty acids 388, 410 Opioid β-receptor 339 665 Origanum majorana 478, 551 Oryza sativa 643 Ox-LDL 539 Oxygen-mediated hydroperoxidation 248 Oxytetracycline 255 P Plasmodium berghei 251 Plasmodium falciparum 227, 231, 241, 242, 245, 255, 260 Chloroquine-resistant 260 Plasmodium lophurae 254 Plasmodium vivae 254 Plasmodium vivax 254 Plasmodium yoelii 255 Paclitaxel 67, 635, 639, 640, 643 Paeonia lactiflora 566 Palau’amine 504 Panax ginseng 542 Papaver somniferum 47 Parkinson’s disease 343 Passiflora incarnata 478 Patrician A 77 Pelletier and Caventou 226 Peltalosa 577 Penicillin 609 Penicillium brevicompactum 61 Peptic ulcer disease 476 Peroxide linkage 311 Peroxyplakoric acid 260 Peruvoside 640, 641 Peucedanum japonicum 571 PfATPase6 245 Pharmaceuticals 603–605 Pharmacokinetics 349 b1214_Index.qxd 8/24/2011 12:53 PM Page 666 b1214 Bioactive Natural Products 666 Index Phenolic compound 632 Phlorizin 64 Photoxidation 248, 249 Phyllostachys nigra 561 Physcomitrella patens (P patens) 634, 644 Physostigma venenosum 374 Phytostanol 415 Phytosterin 415 Piliostigma reticulatum 449 Piliostigmol 449 Pilot plant development 615, 616 Pimecrolimus 57 Pimpinella anisum 478 Piperaquine 257 Protein kinase A (PKA) 206 Placebo 375 Pladienolide D 79 Plakortis sp 260 Plantago lanceolata 508 Plasmodium falciparum 224, 311, 314 Platelet-activating factor (PAF) 341 Plitidepsin (Aplidin) 84 Polymorphonuclear leukocyte (PMNL) 347 Pneumocystis carinii 314 Podophyllotoxin 641, 642 Polygala senega 548 Polyunsaturated fatty acids (PNS) 408 Pomegranate juice 378 Pomiferin 275, 278 Poria cocos 544 Porphya yezoensis 203 Post-translational 633, 644 Potato 643, 644 Prazosin 339 Prelog 233 Primaquine 226, 227 Prodigiosin 82 Proliferator-activated receptor (PPAR)-gamma 564 Promoter 632, 633, 636 Propolis 449 Prostaglandin 409 Proštenik 233 Protein tyrosine phosphatase 1B 555, 560 Prunin 549 Prunus avium 448 Psacalium peltatum 577 Psammaplin 281–283, 298 Psammaplin A 85 Psidium guajava 447 Psoracorylifol 486 Psoralea corylifolia 482, 491 Psoriasis 502 Pterocarpus marsupium 567 Pterostibene 567 Pueraria lobata 562, 566 Puerariafuran 566 Pulsed amperometric detector (PAD) 315 Pycnogenol creme 509 Pyroquine 227 Q Qing Huo Yi Hao 524 Qinghao plant 242 Qinghaosu 242 Quantitative structure–activity relationship (QSAR) 16 Quercetin 451, 553, 560 b1214_Index.qxd 8/24/2011 12:53 PM Page 667 b1214 Bioactive Natural Products Index Quercetin 3-methyl ether 482 Quercitrin 563 Quinacrine 226, 227 Quinicine 232 Quinidine 237 Quinine 7, 223, 225–228, 231, 232, 235–237, 247, 257, 260 Synthesis 233 Quinoline alkaloids 487 Quinoline–peroxide hybrid 241 Quinolone 487 Quinone 254 Quinotoxine 232, 233, 236 Synthesis (by Louis Pasteur) 232 R Rabdosia trichocarpa 480 Rabe 233 Radicamine A 528 Radicamine B 528 Ramoplanin 73 Raphanus sativus 483 Renin–angiotensin system (RAS) 202 Rat lens aldose reductase 557 Reactive oxygen species (ROS) 245 Red wine 485 Renin 204 Reserpine (Rauwolfia serpentina) 372 Resistance-counteracting functionality 257 Resochin 227 Resveratrol 64, 383, 485, 486, 565 Retapamulin 36 Rhetsinine 524 Rheum undulatum 576 667 Rhodiola rosea 451 Rhus verniciflua 566 Rice 636, 643 Rivastigmine 375 Rohitukine 69 Rolitetracycline 255 Romidepsin 45, 273, 275, 290–293, 297 Rosmarinus officinalis 478 Rosuvastatin calcium 56 Rottlerin 482 Rubriflorins A–C 512 Rutin 508, 549, 553 S (S)-4-Vinylbutyrolactone 236 Saccharomyces cerevisiae 249 Saccharopolyspora erythraea 31 Salacia chinensis 546 Salacia reticulata 572, 579 Salacinol 579 Salicornia herbacea 557 Salicylic acid derivatives 486 Salinispora tropica 260 Salinosporamide A 81, 260 Salix alba Salvia miltiorrhiza 539, 568, 640 Salvia plants 377 Sambucus ebulus 478 Sanguinaria canadensis 487 Saponins 507 Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 245 SERCA-based mechanism 246 Saxitoxin 504 Schistosoma sp 314 Schizont 255 b1214_Index.qxd 8/24/2011 12:53 PM Page 668 b1214 Bioactive Natural Products 668 Index Schmid and Hofheinz 250 Schulzeines A–C 533 Scopolamine 641, 643 Scutellarein 551 Scutellaria baicalensis 448, 551 Scutellaria radix 452 Secoisolariciresinol 572 Secondary metabolite 312, 313, 632, 635, 637, 638 Selaginella tamariscina 464 Selenium 413 Semi-synthesis 634, 639, 640 Serpentine 638 Sesame 203 Sesquiterpene lactones 479 Shikonin 641–643 Sibara virginica 483 Silybin 70 Silybum marianum 404 Silymarin 337, 549 Sirolimus 42, 54, 81 Skin disease 499, 501, 507 Smallpox virus 644 Sophora flavescens 457 Sophora japonica 508 Sophoraflavanone G 457 Sophoramine 374 Spirotryprostatin A 504 Spiruchostatin 291–293 Spirulina 512 Spleen megakaryocytes 434 Staurosporine 78, 81 Stelechocarpus cauliflorus 556 Stereoisomers 632, 645 Stereoselective synthesis of quinine 237 Sterol 489 Stevia rebaudiana 537 Stevioside 538, 539 Stipulin 447 Stork 235 Streptomyces aureofaciens 32 Streptomyces cattleya 27 Streptomyces hygroscopicus 42 Streptomyces peucetius var caesius 40 Streptomyces roseosporus 30 Streptomyces sp H668 260 Streptozotocin (STZ) 339 Strictosidine 634 Strictosidine synthase 634 Suberoylanilide hydroxamic acid (SAHA) 275, 298, 290, 291, 297, 298 Sulforaphane (SFN) 275, 278, 279, 298, 299 Sulfuretin 566 Supercritical fluid 316, 317 Superoxide dismutase (SOD) 338 Swartzia polyphylla 455 Swerchirin 573 Swertia chirayita 573 T T3.5 257 Talinum paniculatum 533 Tau protein 371 Taxadiene 634, 637, 640 Taxiresinol 572 b1214_Index.qxd 8/24/2011 12:53 PM Page 669 b1214 Bioactive Natural Products Index Taxol 319, 325, 372 Taxus 639, 640, 643 Taxus baccata 634, 637 Taxus brevifolia 639 Taxus chinensis 639 Taxus cuspidate 640 Taxus mairei 639 Taxus yunnanensis 572 Tea tree oil 508 Tebuquine 227 Tecoma stans 527 Tecomine 527 Tectona philippinensis 447 Telavancin 37 Telithromycin 31 Temsirolimus 41 Terminalia spinosa 478 Terpene 479 Terpenoid 536, 632, 640 Tert-butylhydroperoxide (tBHP) 337 Tetracera scandens 554 Tetracycline 255 Tetramethylpyrazine 524 Tetraoxacycloalkanes 254 Tetrodotoxin 86 Theophylline 294 Thera wise 503 Thevetia peruviana (T peruviana) 640 Thin layer chromatography (TLC) 314 Thrombocythemia 228 Thrombosis 645 Tiacumicin B 75 Tigecycline 31 Tiotropium bromide 54 Tobacco 636, 637, 643, 644 Tomato 634, 639, 643 669 Topsentin 503, 504 Toxoplasma gondii 314 Trabectedin 42 Tumor necrosis factor-α–related apoptosis-inducing ligand (TRAIL) 344 [Trans-2-[4-(4-chlorophenyl) cyclohexyl]-3-hydroxy-1,4naphthalenedione 254 Transient bradycardia 246 Trapoxin 289 Tretinoin 509 Tribulus terrestris (T terrestris) 640 Trichostatin (TSA) 284, 285, 288, 290–292, 297, 299 Trioxane 254 Trioxolane 254 Tripodanthus acutifolius 446 Trodusquemine 86 Trophozoites 255 Tumor-associated glycoprotein 72 (TAG 72) 643 U UCN-01 201 82 Umbelliferone 571 Uraria picta 455 Urtica dioica 404 Ursolic acid 511 US Food and Drug Administration (FDA) 17 V Vaccine 633, 643, 644 Vanadium effect 414 b1214_Index.qxd 8/24/2011 12:53 PM Page 670 b1214 Bioactive Natural Products 670 Index Vascular endothelial growth factor (VEGF) 42, 322 Vascular relaxation 205 Vasorelaxant 205, 214 Vinblastine 68 Viscum articulatum 459 Vitamin 411 A 511 B12 386 E 387 Vitex negundo 449 Vorinostat 273, 275, 291 Vascular smooth muscle cells (VSMC) 205 W Wendel 254 White clover 643 William H Perkin 232 Withania somnifera 372, 380 Withanolides 380 Woodward and Doering 233, 235, 237 World Health Organization 476 X Xanthoangelol 564 Xanthones 254, 256 Xen-2174 86 Xylulose-phosphate reductoisomerase (DXR2) 633 Y Yersinia pestis Yew 639 644 Z Zea mays 644 Zeyheria tuberculosa 446 Ziconotide 48 Zinc 403, 413, 511 Zingiber officinale 484 Zingiberene 639 Zolinza 275 Zotarolimus 53 Zuccagnia punctata 459 .. .BIOACTIVE NATUR AL PRODUCTS Opportunities and Challenges in Medicinal Chemistry 8033hc.9789814335379-tp.indd 8/29/11 10:32 AM BIOACTIVE NATURAL PRODUCTS Opportunities and Challenges in Medicinal. .. maintaining the documentation of much of the Greek and Roman knowledge of herbs and natural products and expanding that information with their own knowledge of Chinese and Indian herbal medicine.82... product-based drug candidates undergoing clinical evaluation Natural Products in Traditional Medicine: A Historical Perspective in Brief Natural products (including plants, animals and minerals) have