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Aads. See Aminoacetonitrile Derivatives 363 Index a anaerobic NADH-fumarate reductase AADs. See aminoacetonitrile derivatives system 275 (AADs) anthelmintic discovery ABZ-nitazoxanide 266 medicinal chemistry approaches ABZ-sulfone 260, 265, 266 CODP 242–245 ABZ-sulfoxide 260, 265, 266, 272 intervet multicyclics 235, 238 Acid fast bacilli (AFB) 329, 330 VAChT inhibitors 238, 240, 241 acoziborole 129, 130 new molecules, from patent literature acute fascioliasis 294 232–235 adult flukes 295, 300 anti-bacterial approach 169, 171 adult worms 164, 166, 170–172, 175, antibacterial therapy vs. host directed 180, 190–192, 194–198, 200, 201, therapy 354 206, 207, 254, 290, 293–296, 304 antibody-based therapeutics 67–69 African animal trypanosomiasis (AAT) anticancer drugs 194 118, 119 anti-microbial properties 271 albendazole 2, 3, 9, 169, 171, 227–229, metallo-organic ruthenium 257, 272, 275, 303 complexes 271 Alpha-1-acid glycoprotein (AGP) proteasome inhibitor 271, 273 203, 212 anti-foodborne trematode drugs 304, α-difluoromethylornithine 265 311 17-α-ethynylestradiol 298 anti-fungal agent 260 Alpinia nigra 307, 311 anti-fungal compound amphotericin B Alveolar echinococcosis (AE) 253 desoxycholate (cAMB) 267 benzimidazole treatments 257, anti-infective agents 259–261 anti-echinococcal activities 267 clinical presentation 255, 257 anti-malarial drugs 268 Aminoacetonitrile derivatives (AADs) extracellular protozoan parasites 233, 234, 238 267 patents 233 intracellular protozoan parasites amino-acetonitrile linker 234 267 amino-malononitrile linker 234 anti-infective thiazolide 260 amino ozonids 267 anti-malarial compounds 267 amino-pyrazole 147, 148 anti-malarial drugs 268 amphotericin B 2, 3, 7, 140, 143, 144, antimalarials dihydroartemisinin 267 148, 260, 267, 272, 275 anti-metacestodal activity 271 Neglected Tropical Diseases: Drug Discovery and Development, First Edition. Edited by David C. Swinney and Michael P. Pollastri. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA. 364 Index antimicrobial susceptibility Brugia testing 331 B. malayi 172–175, 177, 268 antimycobacterial drugs 329 B. patei 268 antineoplastic properties 269 Buruli ulcer (BU) 327 antiparasitic pharmaceuticals 230, 232 clinical studies 336, 338 antischistosomals 190–192, 194–196, results 336, 338 204, 206–215, 195–200 therapeutic approach 338 anti-tuberculosis drug candidate treatment, BU lesions 338 335 compound screening 336 anti-tumor effects 270 current treatments artemisinin 267 antibiotic treatment, for pregnant artemisinin-derivatives 267 women 328 artemisinin peroxides 267 antibiotic treatment, in Australia artesunate 190, 191, 267 328 arylmethylamino steroids (AASs) 212, standard antibiotic treatment 328 214 diagnostics 329–330 Ascaridia galli 234, 235, 243 discovery models Ascaris lumbricoides 227–229 in vitro test formats 330–331 ATP-binding cassette (ABC) 298 in vivo test formats 331–332 auxotrophies 275 future directions 338–339 avermectins 170, 175, 336, 337 preclinical profiling 332 preclinical profiling, antibiotics b 332 BCX4430 29, 33, 68, 71, 72 repurposing, tuberculosis drug benzimidazoles (BZD) 173, 174, 260, candidates 332, 335–336 266, 272, 275 unmet needs 329 benzimidazole chemotherapy 259 benzimidazole derivatives 303 c benzimidazole monotherapy 228 Caenorhabditis elegans 189, 240, 302 benznidazole 2, 3, 96, 97, 99, 101, 106, Caenorhabditis elegans model 302 107 carboxamides 129, 212, 233–235 β-tubulin genes 260, 266 carvacrol 274 Biarylalkyl carboxylic acids (BACAs) celgosivir 24 190, 206–212, 214 cell-based assays, Ebola virus disease Biarylethylamides (BAEAs) 233, 234 (EVD) 54 bi-cyclic spiropiperidine urea 241 cell-based ZIKV assays 25 bilateral symmetry 290 ceracariae 293 Bilharzid 297 cercariae 290, 291, 293–296 Biltricide® 297 cerebral cholesterosis 273 biochemical® assays 26–28, 307, 308, cerebral invasion 299 310 cerebral paragonimiasis 299 bithionol 304 cestodes 261, 268, 273, 275, 297 blood-streaked pneumonia-like sputum cetrimide 272 295 Chagas disease (CD) boron derived benzimidazoles 175 bioluminescent imaging (BLI) mouse bortezomib 273 model 97 bortezomib-mediated inhibition 271 compound selection 98 Index 365 and identification of potential Cutaneous leishmaniasis (CL) hits/starting points 98 141–143 mechanism 106–107 cyclic AMP (cAMP) 127 model 96–107 1,3-cyclohexanedioic acid 235 overview 95–96 2-(cyclohexylcarbonyl)-1,2,3,6,7,11b- site of action 103–106 hexahydro-4H-pyrazino[2,1-a] sterile cure 96–107 isoquinolin-4-one 297 in vitro assays to guide structural Cyclooctadepsipeptides (CODP) optimisation 101–103 176–177, 242–245 Chenodeoxycholic acid (CDCA) cyclosporin 272, 273, 352, 357 273 Cyp450 Chinese Food and Drug Administration enzyme 266 228 inhibitors 298 6-chloro-5-(2,3-dichlorophenoxy)-2- cyst dimension 255 (methylthio) benzimidazole) Cystic echinococcosis (CE) 253 299 benzimidazole treatments 257, chloroform 297, 302, 305, 308 259–261 chloroquine 24, 265, 304 clinical presentation 255–257 Cholangiocarcinoma (CCA) 293, 294, cytostatic drugs 270 299 cytotoxicity 6, 25, 54, 127, 130, 175, cholangitis 293, 294 195–197, 199, 261, 267, 268, 271 cholecystitis 293, 294 cytotoxic properties 269 cholelithiasis 294 chronic clonorchiasis 293 d chronic fascioliasis 294 Diethylcarbamazine (DEC) 167–171 chronic mycobacterial infection 349 digenean trematodes 290 chronic opisthorchiasis 293 Dihydroorotate dehydrogenase cimetidine 298 (DHODH) 24 clarithromycin 268, 269, 328, 329, dimethylformamide 302 332–334, 336–338, 352, 354, 356 dimethylsulfoxide 297 clofazimine 2, 3, 192, 193, 334, 336, di-N-aryl-diguanidino compounds 350–354, 356, 357 267 clonorchiasis 293, 298, 301 diphenylhydramine 298 Clonorchis sinensis 290, 291, 293, 294, diplostomiasis 295 303, 307 diplostomidae 295 2’-C-methylated nucleosides 32 direct acting antibacterial therapy Cocos nucifera 305, 308, 311 350–355 combination chemotherapy 228, 229 direct-acting antivirals 28, 67–74 Commiphora molmol 307, 309, 311 direct acting approach 169–170 Contrast enhanced ultrasound (CEUS) direct antiviral agents 24–25 257 Dirofilaria immitis 234, 235, 238 Cooperia curticei 234 Disability adjusted life years (DALYs) corallopyronin A 178–180 165, 227, 289, 293, 295 cotrimoxazole 336 disk-diffusion testing 331 Crassotrea gigas 296 Distocide 297 crustacea 291, 294 doxorubicin® 269 366 Index Droncit 297 in vitro and in vivo models 261, 263, Drosophila® melanogaster 238 264 drug discovery efficiency 3–7 Echinococcus 253 drug discovery strategies 1–10, 289 E. canadensis 253 drug level-monitoring 260 E. equinus 253 drug repurposing 95, 127, 128, 148, E.felidis 253 190–194, 213, 264–274, 312, E. granulosus sensu lato 253 332 E. granulosus sensu stricto 253 treating AE E. intermedius 253 anti-cancer drugs 269–271 E. multilocularis genome 260 anti-infective agents 265–269 E. multilocularis metacestodes 256, treating CE 272–274 260, 261, 264–271 Drugs for neglected diseases initiative E. oligarthrus 253 (DNDi) 9, 10, 98, 108, 123, 125, E. ortleppi 253 126, 129, 144, 145, 147–150, 153, E. vogeli 253 173, 177, 188, 229, 244, 338 Echinococcus granulosus 253, 254, 261, 267 e biological feature 254–255 Ebola virus disease (EVD) metacestodes 255 animal models for efficacy testing Echinococcus multilocularis 253, 254, 54–57 257, 263, 269 cell-based assays 54 biological feature 254–255 challenges and innovations 50–52 metacestodes 255 diagnostic tests 50 Echinostomatidae 295 direct-acting antivirals 67–74 echinostomes 295, 301 genome structure, components, and echinostomiasis 295, 303 replication cycle 52 echinostomes 295, 301 host targets 67 symptoms 295 kinases and phosphatases 60 eflornithine 2, 3, 6, 9, 118–124, 128 non-proteolytic endosomal targets embryonated eggs 293, 296 63–65 embryonation 291, 294 nucleic acid inhibitors 70–71 emodepside 176, 177, 232, 242, 244 nucleoside analogs/polymerase Enzyme linked immunosorbent inhibitors 71–74 assay (ELISA) 51, 54, 125, 169, overview of 49–50 257 priming host immune responses epoxy-activated Sepharose 268 65–67 ethacrynic acid 271 ® protein folding and processing ethyl-N-dimethyl ether 272 60–63 eye lesions 163, 166–168 S-adenosyl-homocysteine hydrolase inhibitors 57–60 f surveillance and research diagnostic Fasciola tools 51 F. gigantica 294, 304, 306, 307, 309 therapeutic strategies F. hepatica 290, 291, 294, 300, 301, host-directed antivirals 57 304–306, 309–311 viral protein interactions 69–70 fascioliasis 2, 293, 294, 303, 304 Echinococcosis 253 fasciolopsiasis 296 Index 367 Fasciolopsis 303 g E. buski 292, 296, 301, 304, 307, 308, Galidesivir (BCX4430) 68, 71, 72 311 γ-carbolines 240, 241 Favipiravir (T-705) 63, 68, 71, 72 genistein 58, 60, 61, 269, 307, 311 Federal Drug Administration (FDA) glibenclamide 273, 274 7, 9, 30, 32, 58, 59, 63, 65, 68, Glutathione-S-transferase (GST) 271 70–72, 96, 140, 142, 143, 189, Gracinia mangostana 306, 308–310 202, 203, 270, 271 Guillain-Barré syndrome (GBS) 19, 21 fenbendazole 9, 260, 266, 272 Gymnophalloides seoi 296 fexinidazole 9, 97, 99, 101, 105, gymnophalloidiasis 296, 299 129–131 gynecomastia 273 F18-fluorodeoxyglucose-positron emission tomography h (FDG-PET) 257 Haemonchus contortus 234, 235, 238, Fite-Faraco staining 353 241–244 flavin monoxygenase 300 Hagenia abyssinica 306–308, 310 Flemingia vestita 307, 311 halogenated benzimidazole 299 Flubendazole (FLBZ) 9, 173–174, 6-areneruthenium 271 272 Heligmosomoides polygyrus 234 Foodborne trematode (FBT) infections Heliothis virescens (tobacco budworm) 289 238 adult worms 290 hemolymphatic stage 118 diagnosis 290 heterocyclic pyrazinoisoquinoline drugs
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