491

Index

a – natural products 96 acetaminophen (APAP)-induced toxicity – patent applications 90, 92 211 – spiro-cyclopropyl group 88, 89 9β-acetoxyparthenolide 329 – tri-substituted cyclohexanes 88, 90 acetyl-CoA 52 aerucyclamides 286, 287, 297 Acinetobacter 12 aglaforbesins 172 Acinetobacter baumannii 395 Aglaia 172 Acinetobacter baylyi 12 aglain 172 Acremonium sp. 286, 290 aguerin B 336 actin filaments 288 AIF, see Inducing Factor (AIF) activators and inhibitors of ADAM-10 189 3, 83 alamethicin 292 activities of immunosuppressants 69 D-alanine racemase 63 acute myeloid leukemia (AML) cells 329 alantolactone 324 acute myeloid leukemia (AML) therapy alborixin 128 329 Alcaligenes faecalis 136 ADAM-10 Alcyonacea (soft corals) 482 – APP and RAGE 93 algae – cancer pathology 86, 87 – biodiscovery hotspots 478 – Curcuma longa (turmeric) 94 – EEZs 478 –diseaseprevention 93 alkaloids 241 – Ginkgo biloba 95 allobeauvericins 286 – ginsenoside Rg1 94 all-trans retinoic acid (ATRA) 327 –greentea 95 allylmalonyl-CoA 50 – neurodegeneration 85 almiramide C 284 – pathological conditions 85, 86 almiramides and dragonamides 282, 283 – physiological roles 85 Alnus crispa 399 – potential drug target 87 Amanita phalloides 216 –structure 85 amebiasis 279 ADAM family of enzymes 83 aminobutyric acid 292, 301 ADAM-10 in cancer pathology 86 3-amino-6-hydroxypiperidone 305 ADAM-10 inhibitors α-aminoisobutyric acid 299 – carbamate based selective inhibitors L-2-amino-8-oxodecanoic acid 281 90 4(S)-amino-2(E)-pentenoic acid 290 – different structural moieties 88 amphomycin 303 – modified, improved inhibitors 88, 89 amyloid beta (Aβ)85

Bioactive Natural Products: Chemistry and Biology, First Edition. Edited by Goutam Brahmachari. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2015 by Wiley-VCH Verlag GmbH & Co. KGaA. 492 Index

amyloid precursor protein (APP) 85, 86, 93, antimalarial activities of flavaglines 191 95 antimutagenic 243 6-O -angeloylenolin 336 antioxidant 397 angiotensin-converting enzyme (ACE) 91 antioxidant activity of 222 phyla 473 antioxidant activity of mangiferin 200 Anopheles 280 antioxidant activity of silymarin 217 Antarctica 479 antioxidants 4 anthocyanins 392 antiparasitic activity of polyether antibiotics antiamoebin I 299 141 antibacterial activity 135, 140 antiproliferative activity 146, 326 antibiotic resistance antiseizure 398 – bioactive natural compounds 9 antituberculosis anti-TB activity 349 –celldeath/stasis 9 antituberculosis potential of calanolides and –GDAs 10 related derivatives 357 – inhibitory activity 9 antiviral 144, 397 –MOA 10 A 282 – in vivo analysis 10 apicidin B 282 anticancer 145, 172, 184, 399 apicidin C 282 anticancer activity, flavaglines apicidin D2 282 – AIF 189 apicidin D3 282 – DNA repair pathway 189 apicidin E 282 – eIF4A 184 apicidin F 282 – EMT 188 apicidins 281 – HSF 188 apicomplexan 288 – kinase C-Raf, activation 186 apoptosis-inducing factor (AIF) 189 – MEF 189 applications of GDA technology 21 – PDAC 186 aquaculture techniques 485, 486, 487 – PHB 184, 186 Arabidopsis thaliana 393 – protein synthesis 188 arginine vasopressin (AVP) 410, 412 – rohinitib 188 arjunolic acid 209, 212 – silvestrol 189 Arnica montana 332 – TXNIP 188 aromatic amino acid biosynthesis 22 – Warburg effect 188 arsenic 212 anticancer activity of sesquiterpenes lactones arsenic-induced myocardial damage 323 209 anticancer parthenolide analogs 329 Artemisia annua 393 anticoagulant 398 Artemisia tournefortiana 333 antidiabetic activity 203, 211 artemisinin 323 antifungal activity 140, 243 artemisinin and Its Derivatives 332 antifungal antibiotics 44 ascomycin 43, 45, 54 anti-herpetic activity 394 – carbon backbone 50, 51 anti-HIV 44, 145 –DIMT 57 anti-HIV potential of calanolides 349 – immunosuppressants 47 anti-inflammatory 190, 397 – macrolide ring structure 49 anti-inflammatory activity of mangiferin – microbial desmethylation 57 201 – pipecolic acid 53 anti-inflammatory and immunosuppressant – shikimate 60 activities, flavaglines 190 ascomycins 45 antileishmanial 243 Aspergillus niger 48 antimalarial activities 142, 144, 191, ATM 189 243 ATR 189 antimicrobial 9, 243, 394 Auletta constricta 288 Index 493 autoimmune diseases 43 – supply issue 474 ayapin 396 biodiversity 473, 481 azathioprines (Imuran) 43, 44 biogeography Azolla imbricata 393 – analysis of chemical diversity 481 – classifications 478 b – definition 474 Babesia sp. 279, 280, 300 BIOLL+® 21 babesiosis 279, 280 biomimetic synthesis of flavaglines 179 Bacillus anthracis 46 biopiracy 483 Bacillus brevis 293 bioproduction, MNPs Bacillus cereus 136 – analysis 487 Bacillus subtilis 12, 136 – drug discovery pipeline 485 Bacteroides fragilis 137 – in toto aquaculture 485 baicalein (5,6,7-trihydroxyflavone) 214 – in situ and ex situ culture methods 486 Baker’s synthesis of (+)-calanolides A and B – pharmaceutical pipeline 484 360 – R& D strategies 485 balgacyclamide A 285 – sustainability and replicability 484 balgacyclamide B 285 – synthetic/semisynthetic analogs 485 balgacyclamide C 285 bioprospecting 473, 478 balgacyclamides 285 – and bioproduction processes 474 barcode 455 – biopiracy 483 basiliximab (Simulect) 43, 44 – description 473 Bcl-2 326 – EEZs 478 beauvenniatins 289, 290 – geographical selection 478 Beauveria bassiana, 286 – invertebrate 482 Beauveria nivea 45, 301 – marine organisms 474 Beauveria sp. 286 biosynthesis 49, 387 beauvericins 286 – ascomycins and tacrolimus 55 beauvericins and allobeauvericins 286 – cyclosporin 61 benthic trawling 483 – flavaglines 174 242, 254 – pathway 388 berberine dimers 248 blue gold 473 berberine–DNA complexation 244 Botrytis cinerea 399 berberrubine 246, 248 bovine serum albumin (BSA) 258 betacellulin 87 brevilin A 37 bioactive metabolites 485 Bryopsis sp. 294 bioactivity 452 Bursaphelenchus xylophilus 396 biodegradable curcumin nanoparticles butyryl-CoA 51, 52 226 biodiscovery, MNPs c – 1940 and 2012 474, 475 Cacospongia mycofijiensis 449 – analysis 487 calanolide-based chemical library – biogeography 474 359 – bioproduction process 474 calanolides 6, 349, 354, 397 – bioprospecting 474 calcimycin 128 – chemical, taxonomical and geographical calcineurin 48 trends 474 Calophyllum sp. 349 – deep-sea and polar areas 474 C. brasiliense 349 – geographical selection 478 C. lanigerum Miq. var. austrocoriaceum – marine organisms 474 349, 397 – remotely operated vehicle (ROV) 475 C. teysmannii 397 – SCUBA 475 C. teysmannii var. inophylloide 349 494 Index

camp cyclic adenosine monophosphate Chondromyces sp. 288 (cAMP) 35, 93 Chrysophyllum cainito 393 cancer 34 chrysosplenol C 394 cancer pathology 86 cinnamate 4-hydroxylase (C4H) 388 cancer signaling in natural product screening Cirsium hypoleucum 394 33 Cladosporium cladosporioides 393 cancer-signaling pathways 2 Clostera cupreata 396 Candida albicans 12, 45 Clostridium perfringens 136, 246, 247 Candida krusei 395 Clostridium septicum 137 Candida neoformans 48 Cnidaria 476, 481 captive breeding (ex situ) 486 coccidiosis 279 carboxypeptidase (CPY) 461 Cochlospermum tinctorium 207 cardiac arrhythmias 209 colensolide 448 cardinalisamides 304 combinatorial chemists 1 cardiomyopathy 209 combinatorial synthesis 443 cardioprotective effects of arjunolic acid Combretum nelsonii 207 208 complexes of ionophores with metal cations Carex distachya 398 130 carmabin A 283 copticine 267 Carpesium faberi 338 coptisine 242 caspase-12 189 corals 479 cationomycin 129 Cordyceps cardinalis 304 CD44 87 Cornus capitata 207 Cdc25A 189 correlation spectroscopy (COSY) 446 CDK4 188 corticosteroids 44 cell wall/membrane stability assays 10 corticotropin-releasing factor (CRF), CellCept 46 neurokinin 1 (NK1) 410, 411 cellular DNA polymerases 353 costatolide 324, 349 Centipeda minima 336 COSY (correlation spectroscopy) 446 Cephalosporium 299 p -coumarate-CoA 388 cezomycin 128 coumarin murraxocin 396 Chaga’s disease 281 coumarins 387, 388, 396, 397 chalcone isomerase (CHI) 388 – antifungal activity 395 chalcone synthase (CHS) 388 – Boenninghausenia albiflora 396 chemical diversity 474 – Crypsiptya coclesalis 396 chemical genetic analysis 454 – Helianthus annuus 396 chemical genetic interactions 12 – Heracleum candicans 396 chemical genetics and genomics 10, 455 – Matricaria chamomilla 396 chemical genetics and network – Panegrellus redivivus 396 pharmacology in yeast for target – pharmacological properties 397 identification 455 – Plecoptera reflexa 396 chemical genomics 9, 11 – Prangos uloptera 396 chemical modifications 137 p -coumaroyl-CoA 388, 389 chemical syntheses 174 CP-78545 131 chemically-defined media 67 C-Raf 186 ChemProteoBase program 462 Crohn’s disease 43 chiral spiro-cyclopropyl 88 crotonyl-CoA 52 chitosan 22 Crypsiptya coclesalis 396 Chk1/Chk2 (Chk, checkpoint kinase) 189 Cryptococcus neoformans 48 chlamydocin 281, 282 cryptosporidiosis 279 (CCK). 410, 418, 420 Cryptosporidium 279, 301 chondramides and jaspamides 288, 289 Cryptosporidium parvum 142 Index 495

Crystal structure d – antibiotic 6016 thallium salt. 127 2D difference gel electrophoresis (2D-DIGE) – cationomycin thallium salt. 129 462 – 2 : 1 complex of calcimycin with the daclizumab (Zenapax) 43, 44 magnesium cation. 128 data analysis, GDA – dimeric complex of lasalocid with barium – chemogenomic GDA screens 16 cation 121 – clustering of chemical genomic data 16 – dimeric complex of lasalocid with silver – colony size 15 cation 120 –cytoscape 17 – dimeric complex of lasalocid with – drug likeness 17 strontium cation 122 –effluxpumps 17 – 28-epimutalomycin potassium salt. 127 – gene ontology (GO) 16 – ionomycin complex with the calcium – GeneMANIA 17 cation 130 – genetic and protein-protein interaction – lasalocid acid complex with 16 1,1,3,3-tetramehylguanidine. 123 – g:profiler 17 – monensin complex with Co+ cation. 113 – growth detector (GD) 15 – monensin 1-naphtylmethyl ester with the – inhibitory compound 16 lithium perchlorate 116 –proteincomplex 16 – monensin lithium salt 113 – SGAtools 16 Curcuma longa (turmeric) 94, 221 deeper habitats 484 deep-sea area 474, 475 curcumin 94, 223 dehydrocostus lactone 324 cyanidin-3-O -glucoside 393, 395 deletion mutant array (DMA) 460 cycloaspeptides 301, 302 delphinidin-3-O -glucoside 393 cyclolinopeptides 301, 302 delta 87 cyclooxygenase (COX-2) 201 -demethyl-12-oxo calanolide AI cyclopenta[b]benzofurans 172 355 cyclosporin A 43, 63, 301 deoxyribonucleic acid (DNA) 243, 244, 261 – antifungal agent 45 DHCHC from shikimic acid in Streptomyces – antiviral activity 70 hygroscopicus 61 –biosynthesis 62 diabetes and curcumin 225 – calcineurin 47, 48 diabetes and silymarin 219 – immunosuppressant 47, 70 diabetic nephropathy 203 – malaria parasite 70 2,4-diacetylphloroglucinol (DAPG) 22 – organ transplantation 43 α,β-diaminobutyric acid 303 – side effects 45 Diaporthe phaseolorum 393 –yeasts 48 Didemnum molle 302 cyclosporin biosynthesis 62 dihydrocyclohexylcarbonyl-CoA 64 cyclosporins 43, 300 (5,6-dihydro-9,10-dimethoxybenzo[g]- cynaropicrin 323, 336 1,3-benzodioxole 5,6-aquinolizum) 243 cysteine 53 11α,13-dihydrohelenalin acetate (DHA) L-cysteine 331 331 cystic fibrosis transmembrane receptor 11,13-dihydrovernodalin 324 (CFTR) 457 dihydroxy-cyclohexanecarboxylic acid cytochrome P450 monoxygenase (C3’H) (DHCHC) 58 388 4,5-dihydroxycyclohex-1-enecarboxylic acid cytoprotective activity, flavaglines 190 51 – FL3 191 1,25-dihydroxyvitamin D3 326 – rohitinib 191 7,12-dimethylbenz(a)anthracene (DMBA)- – SAR 191 324 cytoscape 17 diploid yeast heterozygous strain 18 496 Index

Dipteryx odorata 390 enniatins 289, 290 disabling symptoms 414 enniatins and beauvenniatins 289 discovery 44 Entamoeba 279 DNA and RNA polymerization assays 10 – E. hirae 136 DNA barcodes 456 – E. histolytica, 289 DNA polymerization assay 10 – E. invadens 289 DNA topoisomerase II 247 enthalpy–entropy compensation 254, 263 Dobler’s racemic synthesis of rocaglamide enzyme inhibition assays 10 178 ephrin 87 dog toxicity 45 epidermal growth factor (EGF) 84 dolastatin 10 and 15 290 epigallocatechin-3-gallate (EGCG) 95 doxorubicin 85 epistasis 12 doxorubicin induced cardiac apoptosis 209 epithelial-mesenchymal transition (EMT) doxorubicin-induced cardiotoxicity 191, 188 215 epoxy(4,5α)-4,5-dihydrosantonin 324 doxorubicin-induced oxidative damage 220 ERK, see extracellular-signal-regulated DPPH radical–scavenging activity 214 kinase (ERK) 186 dragomabin 283 Escherichia coli 12, 52, 246 dragonamides 283 – advantages and disadvantages 18 Dreyer’s total synthesis of (±)-calanolides A, –GDA(Keiocollection) 18 C, and D 360 – host tissue/agricultural crops 18 drug development 464 – PCR-based transformation 18 drug discovery 473, 485 –prokaryotic 18 drug screening assays in HTS 35 – λ red recombinase system 18 dynorphins 420 –RNAi 19 – single-gene deletion strains 19 e – solid/liquid culture 17 eat shock factor (HSF1) 188 – yeast 18 E-cadherin 87 17-β- 375 efflux pumps 17 receptor signaling 377 efrapeptins 299 estrogen receptors (ERs) 375 EGFR (growth-factor-induced epidermal ethylmalonyl-CoA 52 P13Ks etoposide 92 phosphatidylinositol 3-kinase), Wnt 34 eudesmenolides 339 eIF4A, see eukaryotic initiation factor-4A Eugenia uniflora 393 (eIF4A) 184, 188 eugenol 22 Eimeria sp. 279, 301 eukaryotic initiation factor-4A (eIF4A) 184 Eimeria brunette 142 eupalinin 333 Eimeria necatrix, Eimeria acervulina, eupatoriopicrin 323 Eimeria maxima 142 Eupatorium chinense L. 333 Eimeria tenella 282 69 Eimeria tenella, apicidin D1 282 EvoTec Opera automated confocal Elephantopus mollis 338 microscope 461 Elysia rufescens 294 exclusive economic zone (EEZ) 478, 479 Emericellopsis 299 extracellular-signal-regulated kinase (ERK) EMT, see epithelial-mesenchymal transition 186 (EMT) 188 enantioselective total synthesis 369 f endogenous steroids 377 fatty acid synthase (FAS) 50 endothelial growth factor (EGF), TGF-β ferensimycin A 131 (transforming growth factor) 184 ferensimycin B 131 end-stage renal disease (ESRD) 203 fermentation and nutritional studies 65 Index 497

FK520 46 gene deletion arrays (GDA) FK506-binding protein 12(FKBP12) 47 – advantages 12, 22 FL23 191 – C. elegans 19 FL3 191 –andDAPG 22 flavaglines 4, 171, 173 – E. coli 17–19 – aglaforbesins and aglains 174, 179 –andGRAS 20 – anticancer activity 187 – and haploinsufficiency mutant profiling – anticancer mechanisms 187 (HIP) 18 – Aglaia (Meliaceae) 172 – and homozygous mutant profiling (HOP) –murinecancermodels,in vivo activity 18 184, 185 – and methicillin resistant Staphylococcus – natural products 171, 172 aureus (MRSA) 20 – synthetic 172 – and open reading frame (ORF) 11 – targeted therapies 171 – antibiotic-resistant microbial strains 19 flavonoids 387 – antimicrobial activity 20 – anthocyanins 392 –BIOLL+® 21 – biosynthesis 388 – chemogenomic profiles 22 – Arabidopsis thaliana 393 –chitosan 22 – Azolla imbricata 393 –dataanalysis 15 – Cladosporium cladosporioides 393 – diploid yeast heterozygous strain 18 – Medicago truncatula 393 – drug development process 12 – pharmacological properties 394 – epistasis 12 – Pinus species 393 – eugenol 22 – Pseudowintera colorata 393 – genetic interaction 12 – Ulex europaeus 393 –globalmicrobiotia 21 flavonolignans 216 –haploid 18 fluorescence resonance energy transfer – heterozygous diploid and haploid mutants (FRET) 259 11 fluorescence superquenching assays 35 –HIP/HOPplatform 21 fluoride 212 – homologous regions 11 forward and reverse chemical genetics 10 – hypotheses 21 Fox’s synthesis of key intermediate of – identification/validation process 12 (+)-calanolide A 360 – Kanamycin resistance cassette (KanMX) free radical intermediate of arjunolic acid: 11 210 – medicinal properties 21 free radical-scavenging property of – mouse conditional knockout collection i curcumin. 224 23 Friedel–Crafts acylation 360 – paromomycin 22 Frontier’s synthesis of rocaglamide 180 – phytoanticipins and photoalexins 20 Fujimycin, Prograf 43 –plants 20 function in plants 395 – salicylates 21 – S. cerevisiae 14, 17–19 g gene deletion arrays (GDAs) 10, 11 G-protein-coupled estrogen receptor 30 gene knockout collections 11 375 gene ontology (GO) 16 G-protein-coupled receptors 409 geneMANIA 17 G2M block 463 generally regarded as safe (GRAS) 20 (GAL) 415 genetic interaction gallinamide A 10, 290, 291 – buffering system 14 -releasing peptide (GRP) 428 – E. coli 14 GDA technology 2, 11 –definition 12 gene deletion 12 – gene deletions 14 498 Index

genetic interaction (contd.) Helicobacter pylori 21 – gene disruption and parallel pathways 14 Hemiasterella minor 288 – positive/negative (alleviating/aggravating) Hemisteptia lyrata Bunge 336 13 hemoglobin 259 – and quantifying genetics 14 hepatic protection 213 – S. cerevisiae 13 Heracleum candicans 396 – single/double deletions 14 heteronuclear multiple-bond correlation genetics and strain Improvement 63 (HMBC) 448 genistein 383 heteronuclear single-quantum coherence geodiamolides 288 (HSQC) 446, 448 geographical trends high-throughput screening (HTS) 2, 443 – biodiscovery hotspots, marine algae hirsutatins and hirsutellides 291 478 Hirsutella 291 – biogeographic classifications 478 – H. kobayassi 291 – exclusive economic zone (EEZ) 478, – Hnivea 291 479 hirsutellide 291 – intertidal flats and shallow coral reefs (HDAC) 281 481 HMBC spectrum 450 – invertebrates 479, 480 homovanillic acid (HVA) 426 – latitudinal theory 479 homozygous mutant profiling (HOP) 18 – open-ocean and deep-sea 481 HSF, see heat shock factor (HSF) 188 – temperate regions 481 HSQC 446 – tropical and polar regions 480 human α -acid glycoprotein 354 germacranolides 339, 340 1 human African trypanosomiasis (HAT) germacrene A–D 336 281 Giardia 279, 301 human caucasian acute lymphoblastic giardiasis 279 leukemia (CCRF-CEM) 329 Ginkgo biloba 95 human nasopharyngeal cancer cell line ginsenoside 94 (CNE) 338 Gleevec (imatinib) 69 human promyelocytic leukemia (HL-60) cell gliocladium 299 395 global genome-wide single-deletion array human protozoan diseases 5 (GDA) technology 2 hydroxamate derivatives 90 global transposon mutagenesis 10 glumamycin 303 4-hydroxyalkenals (4-HA) 201 GLUT4 glucose transporter 219 hydroxycinnamoyl transferase (HCT) 388 glutathione peroxidase (GPx) 201 L-2-hydroxyisocaproic acid 291 gramicidins 293, 294 D-2-hydroxyisovaleric acid 286 green tea 95 L-2-hydroxyisovaleric acid 291 growth detector (GD) 15 (R)-2-hydroxyisovaleric acid 290 guaianolides 336, 339 [1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6- heptadiene-3,5-dione] 221 h 3-hydroxy-7-methyloctanoic acid) 294 6-hydroxy-4-methyl-8-oxo-L-2- H2O2 -induced apoptosis 215 hanphyllin 324 aminodecanoic acid 304 haploinsufficiency 18 2-hydroxy-3-methylpentanoic acid 298 haploinsufficiency mutant profiling (HIP) 2-hydroxy-3-phenylpropanoic acid 291 18 (E)-7-hydroxy-2,4,6-trimethyloct-4-enoic heat shock factor (HSF) 188 acid 288 helenalin 323, 331 5-hydroxytryptamine (5-HT) 410 heliangolides 322 hyperglycemia 203 Helianthus annuus 396 hyptocretenolides 322 Index 499 i irinotecan 92 IκBα kinase (IKK) 202 iron complexing activity of mangiferin 205 identification of protein targets 462 Isaria farinosa 302 IgM immunoglobulin M receptors 184 Ishikawa’s synthesis of (+)-calanolides A, B, IL-6 87 and D 360 IMD-019064 191 Ishikawa’s total asymmetric synthesis of IMD-026259 190 (+)-calanolide A 360 immunomodulatory effect 202 isoalantolactone and related compounds immunomycin 43, 46, 68 335 immunophilins 43, 44, 72 1-isobutyl-2-[1-pyrrolo-(1,2-a)pyrimidinium- Immunosuppressants 43 2,3,4,6,7,8-hexhydrolethyl]ethylamine immunosuppressants 299 – applications 72 isobutyryl-CoA 52 –ascomycin,see ascomycins 45 isoflavones and coumestans 380 – azathioprine 44 isoquinoline 241 – biological activities 69 isoquinoline alkaloids 5, 241 – cyclosporin A, see cyclosporin A 43, 70 Isoquinoline alkaloids and their analogs –description 43 243, 266 –discovery 44 isothermal titration calorimetry (ITC) 250 –modeofaction 47 Ixempra® 466 – monoclonal antibodies 44 Ixeris chinensis 336 – muromonab CD3 44 ixerochinolide 336 –PTK 69 – , see sirolimus 69 j –tacrolimus,see tacrolimus 69 japonicones 335 immunosuppresssants 2, 43 jaspamide A 288 –biosynthesis 49 jaspamide B 288 –fermentation 65 jaspamides 288, 289 – genetics 63 Jaspis sp 288 – nutritional studies 65 jasplakinolide 288, 289 – strain improvement 63 jatrorrhizine 242 in toto aquaculture 485 jatrorubine 248 in vivo analysis 10 Jurkat T-cell 333 indianomycin 131 iNOS 201 k insecticidal, antifungal, anti-inflammatory, kahalalide A 294 neuroprotective, cardioprotective 172 kahalalide D 294 interleukin IL-2 98 kahalalide F 294 Inula helenium 327 kahalalide F 294 Inula racemosa 339 kahalalide G 294 Inula viscose 334 kahalalides 294 inuviscolide and related compounds 334 kanamycin resistance cassette (KanMX) 11 invertebrates 476 kissing bug 281 – 1990s and 2000s 478 Klebsiella pneumoniae 58 – bioprospecting 479 – discovery of MNP 478 l – microbiome 485 lagunamide A 295 – microorganisms 477 lagunamide B 295 – phylum Porifera and Cnidaria 482 lagunamide C 295 ionomycin 129 lagunamides 295 ionophores with monensin skeleton 125 lasalocid A 108 IP3 (inositol trisphosphate) 35 lasalocid acid 146 500 Index

lasalocid acid A and its derivatives 118 mammalian target of rapamycin (mTOR) lasalocid acid Mannich bases 125 47 lasalocid ester derivatives 124 Mangifera indica Linn. 200 lasalocid ortho -nitrobenzyl ester 125 mangiferin 200 latrunculin A 464 mariculture (in situ) 486 Leandra chaeton 207 marine biodiversity 481, 483 Leishmania sp. 279, 301 – analysis 487 – L. amazonensis 294 – 482 – L. donovani, almiramide A 284 – bioprospecting 481, 482 – L. donovani 284, 285, 294, 298, 291, 303, – cephalopods 482 305 – human society 481 – L. major 300 – industrial applications 481 – L. mexicana, 298 – invertebrate groups, sponges and – L. pifanoi 294 cnidarians 481 leishmaniasis 279, 280 – microorganisms 482 leucinostatin A 304 – phylum Mollusca 482 leucinostatin B 304 – protect 483 leucinostatins 304 – sea snails 482 ”lifetime estrogen exposure” 383 – stony corals 482 Linum usitatissimum 301 marine natural products (MNPs) 8, 473 lipopentapeptides 283 – analytical spectroscopy technologies 487 lipophilicity 322 – biodiscovery, see biodiscovery, MNPs liquid chromatography–tandem mass 474 spectrometry/mass spectrometry – bioprospecting 474 LC–MS/MS 356 – blue gold 473 liver protection 212 – description 473 Luche 369 marine organisms 8, 443 luciferase reporter gene assays 37 marine species 473 luminol-enhanced chemiluminescence 219 Matricaria chamomilla 396 lymphocyte activation 47 matrix metalloproteinase-9 (MMP-9) 329 lymphocytes 48 matrix metalloproteinases (MMPs) 84 Lyngbya sp. 283 mechanism of action (MOA) 2, 9 – Lmajuscula 283, 295 – antibiotic resistance 9 – chemical genetic analysis 10 – chemical genomics 11 m –andGDA,see gene deletion arrays (GDA) macrolide structures 52 11 Magnus’ synthesis of methyl rocaglate by mechanism of action of arjunolic acid 214 acetyl bromide 182 mechanism of cation transport 132 Magnus’ synthesis to access flavaglines 181 Medicago truncatula 393 malaria 279, 280 MEF, see mouse embryonic fibroblast (MEF) malonyl-CoAs 50, 51 189 mammalian cells melanin-concentrating hormone 424 – biological activity 453 Melilotus alba 398 – cell proliferation or cytotoxicity testing membrane-bound estrogen receptor mERα 453 or mERβ 375 – latrunculin A 454 mercury-induced toxicity 205 – peloruside A 454 metabolism of curcumin 222 – pharmacological tools 454 metabolism of silymarin 217 – sulforhodamine B assay 453 metastasis 35 – tetrazolium dye assays 453 methicillin resistant Staphylococcus aureus – trypan blue dye exclusion 453 (MRSA) 20 Index 501

5-methoxydec-9-ynoic acid 298 Mycobacterium smegmatis 136 methoxymalonyl-ACPs 51 Mycobacterium tuberculosis 136 methyl transferase 57 Mycobacterium tuberculosis (Mtb) 357 2-methylaminobutyric acid 296 mycophenolate (CellCept) 43 β-methylaspartic acid 303 mycophenolic acid 46, 69, 70 2-methylbutyric acid 294 Myrciaria cauliflora 393 methylmalonyl-CoA 64, 65 (2R)-methyloct-7-ynoic acid 283 n Michael acceptor 177 N-methyl-D-aspartate (NMDA) 414 Michael-type addition 327 N-cadherin 87 microbial immunosuppresssants 2 naringenin 388, 393 Micrococcus luteus 136 natural products 387 Micrococcus lysodeikticus 246, 247 – bioassay-guided isolation 444 microcyclamide 7806A 287 – chemical structures 446, 447 Microcystis aeruginosa 285, 286, 287 – discovery programs 443 microtubule-stabilizing agent (MSA) 451 – high-throughput screening 443 minichromosome maintenance MCM – polystyrene-divinylbenzene 444, 445 proteins 184 – research divisions 443 minimolide G 338 minimolide H 338 – secondary metabolite fraction 444, 445 minimum inhibitory concentration (MIC) natural products as ADAM -10 activators 357 93 Mitsunobu inversion 369 natural products as ADAM -10 inhibitors Mitsunobu reaction 360 96 modulating ADAM activity 85 natural products in GDAs 19 molecular basis of the distinct SERM action naturally occurring antioxidants 4, 199 381 naturally occurring calanolides 6 molecular geometry 322 Nazarov-type reaction 177 molecular-docking 258 neosiphoniamolide 288 mollamide B 303 neosiphoniamolide A 288 mollamide C 303 network pharmacology 457 mollamides 302 neurodegeneration 85 Mollusca 482 neurokinin A (NKA) 415, 418 monensin 108 neurokinin B. 324, 418 monensin amides 114 neuromodulators 7, 409 monensin and Its derivatives 112 S 425 monensin bioconjugates with amino acids (NPY) 410 115 7, 409 monensin diurethanes 114 423 monensin esters 115 neurotoxic plaques 85 monensin lactones 115 NF-κB 202 monensin O(IV)H group derivatives 114 NF-κB nuclear transcription factor-κB 326 monoclonal antibodies 44 nigericin 64 MorphoBase program 463 nigericin antibiotics 108 mouse embryonic fibroblast (MEF) 189 nitrogen sources 69 MSA, see microtubule-stabilizing agent NMR spectra 446 (MSA) 451 NMR spectroscopy 445 multridrug resistance 192 NMR-guided isolation 447 muromonab (Orthoclone OKT3) 43 nociceptin 424 muromonab CD3 44 nonribosomal peptide synthetase (NRPS) mycalamide A 445 55 Mycale hentscheli 445 notch 87 502 Index

nuclearfactorofactivatedT-cell(NFAT) Penicillium brevicompactum 46 signaling 190 Penicillium glaucum 46 nucleic acid and protein binding aspects Penicillium notatum 20 241 Penicillium stoloniferum 46 nucleotide reverse transcriptase inhibitors pentanoyl-CoA 51 (NRTI) 350 and depsipeptides 5 nutraceutical formulation 395 – alamethicin 292 – almiramides and dragonamides 282 o – antiamoebin I 299 open reading frame (ORF) 11 – apicidins 281 420 – balgacyclamides 285 orexin A. 422 – beauvericins and allobeauvericins 286 orexin B. 420 – cardinalisamides 304 Oscillatoria nigro-viridis, 298 – chondramides and jaspamides 288 Oscillatoria sp. 297 – cycloaspeptides 302 Osmundariacolensoi 448 – cyclolinopeptides 301 oxazepinedione 174 – cyclosporins 300 oxidative stress 219 – dolastatin 10 and 15 290 oxidative stress and antioxidants 200 – efrapeptins 299 oxidative stress–mediated organ – enniatins and beauvenniatins 289 dysfunctions 199 – gallinamide A 290 oxytocin 413 – gramicidins 293 – hirsutatins and hirsutellides 291 p – kahalalides 294 paclitaxel 92, 464 – lagunamides 295 paecilodepsipeptide A 296 – leucinostatins 304 Paecilodepsipeptides 295 – mollamides 302 Paecilodepsipetide A 295 – paecilodepsipeptides 295 Paecilomyces 292 – pullularins 296 – P. cinnamomeus 295 – symplocamide A 305 – P. lilacinus 304 – symplostatin 4 290 – P. tenuipes 286 – szentiamide 297 palmatine 242, 260 – tsushimycin 303 palmatrubine 248 – valinomycin 300 pancreatic ductal adenocarcinoma (PDAC) – venturamides 297 186 – viridamides 298 Panegrellus redivivus 396 – xenobactin 305 Parkinson’s disease 395 peptides capable 91 paromomycin 22 PG490-88 98 parthenin 323 pharmaceutical development 443 Parthenolide 324 pharmaceutical industry 485 Parthenocissus laetevirens 398 pharmacological properties of flavaglines parthenolide and analogs 328 184 pathophysiology 199 PHB, see prohibitin (PHB) 184 pathophysiology of suicidal behavior 409 phenylalanine ammonia lyase (PAL) 388 Pb (II)–induced hepatic damage 206 (3-phenyllactic acid) 296 PCR 11 phenyllactic acid 304 PDAC, see pancreatic ductal phenylpropanoids 7, 387 adenocarcinoma (PDAC) 186 – coumarins 390, 395 Pechmann reaction 360 – flavonoids 388, 392 peloruside A 446, 463, 464, 466 – genetic engineering 400 Penicillium sp. 302 – molecular biology 400 Index 503

– secondary metabolites 387 protection against nephrotoxicity 213 – six-carbon aromatic ring 387 protection against oxidative insult in brain – stilbenes 392, 398 213 phloroglucinol 360 protein synthesis assays 10 Photinus pyralis 37 protein–protein interactions 34 [3+2]-photocycloaddition 182 proteome-wide protein-protein interaction phylogenetic tree 476 analysis 10 phylum Onychophora 473 proteomic analysis on 2D gels 462 phytochemists 1 protoberberines 241 phytoestrogens 375 protozoan diseases 279 phytoestrogens or plant-derived Pseudoguaianolides 339 xenoestrogens 379 pullularin A 296 PI3Ks signaling drug screening 35 pullularin B 296 pinosylvin 3-O -methyl 399 pullularin C 296 pipecolate 52, 53 pullularins 296 pipecolic acid 53, 299, 303 pyranocoumarins 349 plant secondary metabolites 387 plants 387 q Plasmodium sp. 279, 288 Qin’s synthesis of rocaglamide 179 P. berghei 143 quantifying genetic and chemical genetic P. chabaudi 294 interactions 14 P. falciparum 280, 282, 285–294, 295–303, 394, 395 305, 393 quercetin 3-O-β -D-glucuronide 392 P. falciparum, hirsutellide A 292 quercetin-3-O -glucoside 393 P. vinckei-petteri 294 P. viva x 280 r Plecoptera reflexa 396 rapamycin 47 Podachaenium eminens 327 Ras-C-Raf-MEK- 186 polar area 474 reactive oxygen species (ROS) 199, 219, polyether ionophores 3, 107 326, 392 Polyether Ionophores with dianemycin receptor for advanced glycation endproducts skeleton 126 (RAGE) 85, 93 polyketide 288 receptor–ligand binding 34 polymorphic DNA conformations 248 recombinant proteins 37 polymorphonuclear neutrophils (PMNs) reduction 369 219 remotely operated vehicle (ROV) 475 polyphenolic compounds 392 replicability 484 polypurine–polypyrimidine sequences 245 399, 400 polyribonucleotides 254 reverse-transcriptase (RT) 350 polystyrene-divinylbenzene (PSDVB) 444 ribonucleic acids 253 Porco’s biomimetic synthesis of rocaglamide 69 183 ridentin 324 Porco’s synthesis of silvestrol 184 Rizzacasa’s synthesis of silvestrol 183 Porifera 476, 481 RNA inhibition (RNAi) 19 prednisolone (deltasone, orasone) 43 RNA interference (RNAi) 23, 37 prodigiosins 47 RNA polymerization assay 10 prohibitin (PHB) 184 rocaglamide 172, see also flavaglines 172 proline 54 – DNA repair pathway 189 prolylascomycin 54 – Dobler’s racemic synthesis 177 propionyl-CoA 52, 69 – Frontier’s synthesis, Nazarov reaction prostaglandin-E2 457 177, 180 prostate epithelial cells (PrECs). 330 – Magnus’ synthesis 177, 181 504 Index

rocaglamide 172, see also flavaglines (contd.) sesquiterpene lactones 5, 321 – Magnus’ synthesis of methyl rocaglate, shikimate 60 Nazarov reaction 177, 182 shikimic acid 60, 388 – Porco’s biomimetic synthesis 179, 182, silvestrol 182 183 – Porco’s synthesis 183, 184 – Qin’s synthesis 177, 179 – Rizzacasa’s synthesis 182, 183 – Ragot’s synthesis 177, 179 silymarin 216 – Taylor’s synthesis 177, 178 silymarin and hepatoprotection 220 – Trost’s enantioselective synthesis 174, single-gene deletion strains 19 175 sirolimus rohinitib 188 – anti-cancer activities 44 rupicolin A 8-acetate 324 – antitumor activity 69 – biosynthesis 55, 66 s – biosynthetic intermediates 56 Saccharomyces cerevisiae 10, 49, 454 – chemical modification 49 – advantages and disadvantages 18 – core macrocycle 55 – eukaryotic and fungal cells 19 – cyclohexane ring 55 – solid/liquid culture 17 –discovery 45 Saccharomyces Genome Database 461 – FKB12 48 Salacia reticulate 204 – gene cluster 63, 64 salicylates 21 – immunophilin (FKBP12) 47 salinomycin 108, 117, 148 – immunosuppressants 71 salinomycin amide derivatives 118 – lysine stimulation 67 salinomycin ester derivatives 119 – macrolide ring structure 49–51 Salmonella enteritidis 138 –modeofaction 48 Salmonella typhimirium Escherichia coli, – phenylalanine suppression 67 Pseudomonas aeruginosa, 136 – pipecolic acid 52 Salvia metronidazole 21 –PKS 56 Sarawak MediChem Pharmaceuticals 354 – polyketide antifungal agents 70 Sarcina lutea Mycobacterium phlei, – radioactivity 53 Streptomyces cellulosae, Paecilomyces – shikimate 60 varioti, 135 – signal transduction pathwa 47 sarcocystis 279 –TORs 48 Satureja hortensis 21 – unbound prerapamycin 57 Saussurea calcicola 336 sirolimus (rapamycin, Rapamune®)43 Saussurea lappa clarks 324 sirtuin-1 (SIRT1) 93 scaffold proteins prohibitin s-1 and 2 (PHB1, sleeping sickness 281 PHB2) 184 small heat-shock protein Hsp27 191 Schwanna-Bodia-Diamond syndrome small molecule inhibitor (SMI) 455 protein 23 SMI, see small molecule inhibitor (SMI) Scirpus maritimus 398 455 scopoletin 396 snorkeling techniques 475 SCUBA 475 specific enzyme inhibition assays 10 Scutellaria baicalensis 214 sponges 479 sea snails 482 Staphylococcus aureus 135, 139 secondary metabolites 445 Staphylococcus epidermidis 136 selective estrogen receptor modulators STAT (signal transducers and activators of (SERMS) 6, 375 transcription) 34 selectivity index (SI) 332, 357 STAT activation 37 SERMs in the Treatment of STATs signaling drug screening 37 Estrogen-Mediated Cancers 383 Sternberg-Reed (SR) cells 329 Serratia marcescens 47 Stilbella 299 Index 505 stilbenes 387, 398 – T. brucei 284, 300 – Alnus crispa 399 – T. cruzi 281, 291, 298, 305, 306 – biosynthesis 392 – T. evansi 299 – Botrytis cinerea 399 tachykinin (TK)s 415 – Lepus americanus 399 tacrolimus 43, 4, 46 – Parthenocissus laetevirens 398 –calcineurin 48 – pharmacological properties 399 –DIMT 57 – pinosylvin 398 –discovery 46 –pinosylvin3-O -methyl 398 – FKBP12 47 – Scirpus maritimus 398 – FKMT gene 57 – substances classification 389, 392 – gene cluster 63, 64 – Vitis vinifera 399 – immunosuppressants 47, 70, 71 – Yucca periculosa 399 – liver and kidney transplants 44 stimulation of liver regeneration 221 – methyltransferases 68 stony corals 482 – microbial desmethylation 57 Streptomyces sp. 300, 303 –PKS 51 Streptomyces albus 117 Streptomyces cinnamonensis 112 – post-PKS modification 57, 59 Streptomyces fulvissimus 300 –proline 54 Streptomyces hygroscopicus 45, 67 –yeasts 48 Streptomyces tsukubaensis 46 tacrolimus biosynthesis 51 streptozotocin (STZ) 203 tacrolimus-producing strain 50 structural screening approach 445 tagitinin C 324 structure–activity relationships (SARs) Talaromyces wortmannin 36 190, 192 tamoxifen and raloxifene 381 sulforhodamine B (SRB) assay 336 Tanacetum parthenium 328 – of calanolides 355 Taxol® 466 – of sesquiterpenes lactones 340 taxonomic trends superoxide dismutase (SOD) 201 – kingdom and phylum 476 sustainability 484 – marine algae 477 Suzuki reaction 177 – phyla 476, 477 Symploca species 290 – phylogenetic tree 476 symplocamide A 305 – sponges (phylum Porifera) 476 symplostatin 4 290 475 synthesis of flavaglines 174 Taxotere® 466 synthesis of silvestrol 182 Taylor’s synthesis of rocaglamide 176 synthetic chemists 1 TCF (T-cell factor) 36 synthetic genetic array analysis 460 (ToricelTM)69 synthetic inhibitors of ADAM -10 88 tennis ball seam 131 synthetic lethality (SL) 455, 459 Terminalia arjuna 207 szentiamide 297 testicular protection 214 t tetrapeptide portion 283 T-cell activation 47 The discovery of sirolimus 45 T-tropic and monocyte-macrophage tropic thioredoxin-interacting protein (TXNIP) viruses 353 188 Trypanosoma sp. 301 thyroid-stimulating hormone (TSH) – T. b. brucei 292, 303, 304 428 – T. b. gambiense 281 TOP flash reporter gene assays 36 – T. b. rhodesiense, L. donovani 297 topoisomerase I 261 – T. b. rhodesiense 281, 285, 287 292, 303, topotecan 171 304, 306 TOR (target of rapamycin) 47 506 Index

total syntheses of calanolides 360 viridamides 298 tourneforin and derivatives 333 vitamin E, vitamin C, and β-carotene 200 Toxoplasma sp. 279, 301 Vitis vinifera 399 – T. gondii 288, 289 toxoplasmosis 279, 280 w translated associated element 1 (Tae1) 22 W2 chloroquine-resistant Plasmodium triatomine bug 281 strain 283 triptolide 96, 98 Warburg effect 188 Trost’s enantioselective synthesis of Warionia saharae 336 rocaglamide 175 Wnt signaling drug screening 36 Trost’s total synthesis of (−)-calanolides A World Health Organization (WHO) 279 and B 365 Wortmannin 36 Trypanosoma 279 trypanosomiasis 279–281 x tsetse fly 281 X-14868A, X-14868B, X-14868C, and tsushimycin 303 X-14868D 130 tumor necrosis factor (TNF)-α 98 X-14885 128 tumor progression 34 X-206 128 tumorigenesis 35 Xenobactin 305, 306 two-dimensional-NMR experiments 446 Xenorhabdus 305 TXNIP, see thioredoxin-interacting protein Xenorhabdus szentirmaii 297 (TXNIP) 188 Xu’s total synthesis of (±)-calanolide A, B, type 1 diabetes 203 and D 360 type 2 diabetes 204 tyrosine ammonia 388 y tyrosine ammonia lyase (TAL) 388 yeast – barcodes 455 u – carboxypeptidase 461, 462 Ulex europaeus 393 – chemical genetics or genomics 455 unfolded protein response (UPR) system – cystic fibrosis transmembrane receptor 459, 461 457 UPR, see unfolded protein response (UPR) – deletion mutant array 460 system 459 – endoplasmic reticulum stress 461 – EvoTec Opera automated confocal v microscope 461 validation of compound targets by – HTS 455 biochemical analysis 462 – neothyonidioside action 456 valinomycin 300 – network pharmacology 457 various anticancer semisynthetic analogs of – Saccharomyces Genome Database costunolide 327 461 VEGF (vascular endothelial growth factor) – SMI screening 455, 461 188 – synthetic genetic array analysis 460 venom metalloproteases (SVMPs) 84 – synthetic lethality 455, 459, 461 venturamide A 298 – UPR system 459, 461 venturamide B 298 Yucca periculosa 399 venturamides 297 vernodal 324 z vernodalin 323 zampanolide 449, 464 Verticullium hemipterigenum 290 – HMBC screen spectrum 449 vernolide 324 – latrunculin A and mycothiazole vincristine 92 449, 451 viridamide A 298 – microtubule-stabilizing agent 451 Index 507

– MSA 464 Zanthoxylum schinifolium 396 – NMR-based screening protocol 449 zidovudine (AZT) 350 – PSDVB 449 zinc proteases 83 – tubulin 466 zincophorin 131