Abstract
This chapter is designed to demonstrate that compounds derived from nature are still in the forefront of drug discovery in diseases such as microbial and parasitic infections, carcinomas of many types and control of cholesterol/lipids in man. In each disease area we have provided short discussions of past, present and future agents, in general only considering compounds currently in clinical Phase II or later, that were/are derived from nature’s chemical skeletons. Finishing with a discussion of the current and evolving role(s) of microbes (bacteria and fungi) in the production of old and new agents ostensibly produced by higher organisms.
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References
Anonymous (1998) A pictorial history of herbs in medicine and pharmacy. Herbalgram 42: 33–47
Borchardt JK (2002) The beginnings of drug therapy: Ancient mesopotamian medicine. Drug News Perspect 15: 187–192
Chang HM, But PPH (1986) Pharmacology and applications of Chinese Materia Medica. World Scientific Publishing, Singapore
Huang KC (1999) The pharmacology of Chinese herbs. CRC Press, Boca Raton, FL
Dev S (1999) Ancient-modern concordance in Ayurvedic plants: Some examples. Environ Health Persp 107: 783–789
Kapoor LD (1990) CRC handbook of ayurvedic medicinal plants. CRC Press, Boca Raton, FL
NLM, http://www.nlm.nih.gov/hmd/
Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the period 01/1981-06/2006. J Nat Prod 70: 461–477
Newman DJ, Cragg GM, Snader KM (2003) Natural products as sources of new drugs over the period 1981–2002. J Nat Prod 66: 1022–1037
Butler MS (2005) Natural products to drugs: Natural product derived compounds in clinical trials. Nat Prod Rep 22: 162–195
Chin YW, Balunas MJ, Chai HB, Kinghorn AD (2006) Drug discovery from natural sources. AAPS J 8: E239–253
Butler MS (2004) The role of natural products in drug discovery. J Nat Prod 67: 2141–2153
Koehn FE, Carter GT (2005) The evolving role of natural products in drug discovery. Nat Rev Drug Discov 4: 206–220
Sneader W (2005) Drug discovery: A history. John Wiley & Sons, Chichester, UK
Mateles RI (1998) Penicillin: A paradigm for biotechnology. Candida Corporation, Chicago, IL
Newton GGF, Abraham EP (1956) Isolation of cephalosporin C, a penicillin-like antibiotic containing D-α-aminoadipic acid. Biochem J 62: 651–158
Abraham EP, Newton GGF (1961) The structure of cephalosporin C. Biochem J 79: 377–393
Imada A, Kitano K, Kintaka K, Muroi M, Asai M (1981) Sulfazecin and isosulfazecin, novel B-lactam antibiotics of bacterial origin. Nature 289: 590–591
Sykes RB, Cimarusti CM, Bonner DP, Bush K, Floyd DM, Georgopapadakou NH, Koster WH, Liu WC, Parker WL, Principe PA et al (1981) Monocyclic B-lactam antibiotics produced by bacteria. Nature 291: 489–491
Mauger AB, Lackner H (2005) The actinomycins. In: GM Cragg, DGI Kingston, DJ Newman (eds): Anticancer agents from natural products. Taylor and Francis, Boca Raton, Fl, 281–297
Weber JM, Leung JO, Maine GT, Potenz RHB, Paulus TJ, DeWitt JP (1990) Organization of a cluster of erythromycin genes in Saccharopolyspora erythraea. J Bacteriol 172: 2372–2383
Katz L, Donadio S (1993) Polyketide synthesis: Prospects for hybrid antibiotics. Ann Revs Microbiol 47: 875–912
Demain AL (2006) From natural products discovery to commercialization: A success story. J Ind Microbiol Biotechnol 33: 486–495
Baltz RH, Miao V, Wrigley SK (2005) Natural products to drugs: Daptomycin and related lipopeptide antibiotics. Nat Prod Rep 22: 714–741
von Nussbaum F, Brands M, Hinzen B, Weigand S, Habich D (2006) Antibacterial natural products in medicinal chemistry —exodus or revival? Angew Chemie Int Ed 45: 5072–5129
Keating GM, Perry CM (2005) Ertapenem: A review of its use in the treatment of bacterial infections. Drugs 65: 2151–2178
Shah PM, Isaacs RD (2003) Ertapenem, the first of a new group of carbapenems. J Antimicrob Chemother 52: 538–542
Nilius AM, Ma Z (2002) Ketolides: The future of the macrolides? Curr Opin Pharmacol 2: 493–500
Nguyen M, Chung EP (2005) Telithromycin: The first ketolide antimicrobial. Clin Ther 27: 1144–1163
Ubukata K, Hikida M, Yoshida M, Nishiki K, Furukawa Y, Tashiro K, Konno M, Mitsuhashi S (1990) In vitro activity of LJC10,627, a new carbapenem antibiotic with high stability to dehydropeptidase I. Antimicrob Agents Chemother 34: 994–1000
Perry CM, Ibbotson T (2002) Biapenem. Drugs 62: 2221–2234
Kahne D, Leimkuhler C, Lu W, Walsh C (2005) Glycopeptide and lipoglycopeptide antibiotics. Chem Rev 105: 425–448
Iso Y, Irie T, Iwaki T, Kii M, Sendo Y, Motokawa K, Nishitani Y (1996) Synthesis and modification of a novel 1 beta-methyl carbapenem antibiotic, S-4661. J Antibiot 49: 478–484
Anderson DL (2006) Doripenem. Drugs Today (Barc) 42: 399–404
Sum PE, Lee VJ, Testa RT, Hlavka JJ, Ellestad GA, Bloom JD, Gluzman Y, Tally FP (1994) Glycylcyclines. 1. A new generation of potent antibacterial agents through modification of 9-aminotetracyclines. J Med Chem 37: 184–188
Abou-Gharbia M (2002) In: B. Sener (ed): Biodiversity: Biomolecular aspects of biodiversity and innovation utilization. Kluwer Academic, New York, 63–70
Jones CH, Petersen PJ (2006) Tigecycline: First class glycylcycline a new choice for empiric therapy. Drug Discov Today: Therap Strat 3: 137–144
Stein GE, Craig WA (2006) Tigecycline: A critical analysis. Clin Infect Dis 43: 518–524
Sum PE (2006) Case studies in current drug development: ‘glycylcyclines’. Curr Opin Chem Biol 10: 374–379
Page MG (2006) Anti-MRSA beta-lactams in development. Curr Opin Pharmacol 6: 480–485
Ishikawa T, Matsunaga N, Tawada H, Kuroda N, Nakayama Y, Ishibashi Y, Tomimoto M, Ikeda Y, Tagawa Y, Iizawa Y et al (2003) TAK-599, a novel N-phosphono type prodrug of anti-MRSA cephalosporin T-91825: synthesis, physicochemical and pharmacological properties. Bioorg Med Chem 11: 2427–2437
Kawamoto I, Shimoji Y, Kanno O, Kojima K, Ishikawa K, Matsuyama E, Ashida Y, Shibayama T, Fukuoka T, Ohya S (2003) Synthesis and structure-activity relationships of novel parenteral carbapenems, CS-023 (R-115685) and related compounds containing an amidine moiety. J Antibiot 56: 565–579
Kobayashi R, Konomi M, Hasegawa K, Morozumi M, Sunakawa K, Ubukata K (2005) In vitro activity of tebipenem, a new oral carbapenem antibiotic, against penicillin-nonsusceptible Streptococcus pneumoniae. Antimicrob Agents Chemother 49: 889–894
Pace JL, Yang G (2006) Glycopeptides: Update on an old successful antibiotic class. Biochem Pharmacol 71: 968–980
Van Bambeke F (2006) Glycopeptides and glycodepsipeptides in clinical development: A comparative review of their antibacterial spectrum, pharmacokinetics and clinical efficacy. Curr Opin Investig Drugs 7: 740–749
Malabarba A, Ciabatti R, Kettenring J, Ferrari P, Scotti R, Goldstein BP, Denaro M (1994) Amides of de-acetylglucosaminyl-deoxy teicoplanin active against highly glycopeptide-resistant enterococci. Synthesis and antibacterial activity. J Antibiot 47: 1493–1506
Leadbetter MR, Adams SM, Bazzini B, Fatheree PR, Karr DE, Krause KM, Lam BM, Linsell MS, Nodwell MB, Pace JL (2004) Hydrophobic vancomycin derivatives with improved ADME properties: Discovery of telavancin (TD-6424). J Antibiot 57: 326–336
Cooper RD, Snyder NJ, Zweifel MJ, Staszak MA, Wilkie SC, Nicas TI, Mullen DL, Butler TF, Rodriguez MJ, Huff BE et al (1996) Reductive alkylation of glycopeptide antibiotics: synthesis and antibacterial activity. J Antibiot 49: 575–581
Katz L, Ashley G (2005) Translation and protein synthesis: Macrolides. Chem Rev 105: 499–528
Azoulay-Dupuis E, Mohler J, Bedos JP, Barau C, Fantin B (2006) Efficacy of cethromycin, a new ketolide, against Streptococcus pneumoniae susceptible or resistant to erythromycin in a murine pneumonia model. Antimicrob Agents Chemother 50: 3033–3038
Or YS, Clark RF, Wang S, Chu DT, Nilius AM, Flamm RK, Mitten M, Ewing P, Alder J, Ma Z (2000) Design, synthesis, and antimicrobial activity of 6-O-substituted ketolides active against resistant respiratory tract pathogens. J Med Chem 43: 1045–1049
Wang G, Niu D, Qiu YL, Phan LT, Chen Z, Polemeropoulos A, Or YS (2004) Synthesis of novel 6, 11-O-bridged bicyclic ketolides via a palladium-catalyzed bis-allylation. Org Lett 6: 4455–4458
Xiong L, Korkhin Y, Mankin AS (2005) Binding site of the bridged macrolides in the Escherichia coli ribosome. Antimicrob Agents Chemother 49: 281–288
Floss HG, Yu T-W (2005) Rifamycin —mode of action, resistance, and biosynthesis. Chem Rev 105: 621–632
Yamane T, Hashizume T, Yamashita K, Konishi E, Hosoe K, Hidaka T, Watanabe K, Kawaharada H, Yamamoto T, Kuze F (1993) Synthesis and biological activity of 3′-hydroxy-5′-aminobenzoxazinorifamycin derivatives. Chem Pharm Bull (Tokyo) 41: 148–155
Rothstein DM, Shalish C, Murphy CK, Sternlicht A, Campbell LA (2006) Development potential of rifalazil and other benzoxazinorifamycins. Expert Opin Investig Drugs 15: 603–623
Suchland RJ, Bourillon A, Denamur E, Stamm WE, Rothstein DM (2005) Rifampinresistant RNA polymerase mutants of Chlamydia trachomatis remain susceptible to the ansamycin rifalazil. Antimicrob Agents Chemother 49: 1120–1126
Ciabatti R, Kettenring JK, Winters G, Tuan G, Zerilli L, Cavalleri B (1989) Ramoplanin (A-16686), a new glycolipodepsipeptide antibiotic. III. Structure elucidation. J Antibiot 42: 254–267
Walker S, Chen L, Hu Y, Rew Y, Shin D, Boger DL (2005) Chemistry and biology of ramoplanin: A lipoglycodepsipeptide with potent antibiotic activity. Chem Rev 105: 449–476
Freeman J, Baines SD, Jabes D, Wilcox MH (2005) Comparison of the efficacy of ramoplanin and vancomycin in both in vitro and in vivo models of clindamycin-induced Clostridium difficile infection. J Antimicrob Chemother 56: 717–725
Sunenshine RH, McDonald LC (2006) Clostridium difficile-associated disease: New challenges from an established pathogen. Cleve Clin J Med 73: 187–197
Breukink E, de Kruijff B (2006) Lipid II as a target for antibiotics. Nat Rev Drug Discov 5: 321–332
Fang X, Tiyanont K, Zhang Y, Wanner J, Boger D, Walker S (2006) The mechanism of action of ramoplanin and enduracidin. Mol BioSyst 2: 69–76
Tiyanont K, Doan T, Lazarus MB, Fang X, Rudner DZ, Walker S (2006) Imaging peptidoglycan biosynthesis in Bacillus subtilis with fluorescent antibiotics. Proc Natl Acad Sci USA 103: 11033–11038
Pankuch GA, Lin G, Hoellman DB, Good CE, Jacobs MR, Appelbaum PC (2006) Activity of retapamulin against Streptococcus pyogenes and Staphylococcus aureus evaluated by agar dilution, microdilution, E-test, and disk diffusion methodologies. Antimicrob Agents Chemother 50: 1727–1730
Yan K, Madden L, Choudhry AE, Voigt CS, Copeland RA, Gontarek RR (2006) Biochemical characterization of the interactions of the novel pleuromutilin derivative retapamulin with bacterial ribosomes. Antimicrob Agents Chemother 50: 3875–3881
Schlunzen F, Pyetan E, Fucini P, Yonath A, Harms JM (2004) Inhibition of peptide bond formation by pleuromutilins: The structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin. Mol Microbiol 54: 1287–1294
Hochlowski JE, Swanson SJ, Ranfranz LM, Whittern DN, Buko AM, McAlpine JB (1987) Tiacumicins, a novel complex of 18-membered macrolides. II. Isolation and structure determination. J Antibiot 40: 575–588
Theriault RJ, Karwowski JP, Jackson M, Girolami RL, Sunga GN, Vojtko CM, Coen LJ (1987) Tiacumicins, a novel complex of 18-membered macrolide antibiotics. I. Taxonomy, fermentation and antibacterial activity. J Antibiot 40: 567–574
Coronelli C, White RJ, Lancini GC, Parenti F (1975) Lipiarmycin, a new antibiotic from Actinoplanes. II. Isolation, chemical, biological and biochemical characterization. J Antibiot 28: 253–259
Omura S, Imamura N, Oiwa R, Kuga H, Iwata R, Masuma R (1986) Clostomicins, new antibiotics produced by Micromonospora echinospora subsp. armeniaca subsp. nov. I. Production, isolation, and physico-chemical and biological properties. J Antibiot 39: 1407–1412
Swanson RN, Hardy DJ, Shipkowitz NL, Hanson CW, Ramer NC, Fernandes PB, Clement JJ (1991) In vitro and in vivo evaluation of tiacumicins B and C against Clostridium difficile. Antimicrob Agents Chemother 35: 1108–1111
Ackermann G, Loffler B, Adler D, Rodloff AC (2004) In vitro activity of OPT-80 against Clostridium difficile. Antimicrob Agents Chemother 48: 2280–2282
Credito KL, Appelbaum PC (2004) Activity of OPT-80, a novel macrocycle, compared with those of eight other agents against selected anaerobic species. Antimicrob Agents Chemother 48: 4430–4434
Finegold SM, Molitoris D, Vaisanen ML, Song Y, Liu C, Bolanos M (2004) In vitro activities of OPT-80 and comparator drugs against intestinal bacteria. Antimicrob Agents Chemother 48: 4898–4902
Sergio S, Pirali G, White R, Parenti F (1975) Lipiarmycin, a new antibiotic from Actinoplanes III. Mechanism of action. J Antibiot 28: 543–549
Jenssen H, Hamill P, Hancock RE (2006) Peptide antimicrobial agents. Clin Microbiol Rev 19: 491–511
Marr AK, Gooderham WJ, Hancock RE (2006) Antibacterial peptides for therapeutic use: Obstacles and realistic outlook. Curr Opin Pharmacol 6: 468–472
MIGENIX Annual Report (2006). Available at http://www.migenix.com
Sader HS, Fedler KA, Rennie RP, Stevens S, Jones RN (2004) Omiganan pentahydrochloride (MBI 226), a topical 12-amino-acid cationic peptide: spectrum of antimicrobial activity and measurements of bactericidal activity. Antimicrob Agents Chemother 48: 3112–3118
Mechlinski W, Schaffner CP, Ganis P, Avitabile G (1970) Structure and absolute configuration of the polyene macrolide antibiotic amphotericin B. Tetrahedron Lett 11: 3873–3876
Borowski E, Zielinski J, Ziminski T, Falowski L, Kolodziejczyk P, Golik J, Jereczek E (1970) Chemical studies with amphotericin B. Tetrahedron Lett 11: 3909–3914
Chong CN, Rickards RW (1970) Macrolide antibiotic studies. XVI. The structure of nystatin. Tetrahedron Lett 11: 5145–5148
Borowski E, Zielinski J, Falowski L, Ziminski T, Golik J, Kolodziejczyk P, Jereczek E, Gdulewicz M, Shenin Y, Kotienko T (1971) The complete structure of the polyene macrolide antibiotic nystatin A1 Tetrahedron Lett 12: 685–690
Pandey RC, Rinehart KL (1976) Polyene antibiotics. 7. C-13 Nuclear magnetic resonance evidence for cyclic hemiketals in polyene antibiotics amphotericin-B, nystatin-A1, tetrin-A, tetrin-B, lucensomycin, and pimaricin. J Antibiot 29: 1035–1042
Grove JF, MacMillan J, Mulholland TPC, Rogers MAT (1952) Griseofulvin. Part IV. Structure. J Chem Soc: 3977–3987
Morrison VA (2006) Echinocandin antifungals: Review and update. Expert Rev Anti Infect Ther 4: 325–342
Turner MS, Drew RH, Perfect JR (2006) Emerging echinocandins for treatment of invasive fungal infections. Exp Opin Emerg Drugs 11: 231–250
McCormack PL, Perry CM (2005) Caspofungin: A review of its use in the treatment of fungal infections. Drugs 65: 2049–2068
Chandrasekar PH, Sobel JD (2006) Micafungin: A new echinocandin. Clin Infect Dis 42: 1171–1178
Vazquez JA, Sobel JD (2006) Anidulafungin: A novel echinocandin. Clin Infect Dis 43: 215–222
Aperis G, Myriounis N, Spanakis EK, Mylonakis E (2006) Developments in the treatment of candidiasis: More choices and new challenges. Expert Opin Investig Drugs 15: 1319–1336
Andes D, Marchillo K, Lowther J, Bryskier A, Stamstad T, Conklin R (2003) In vivo pharmacodynamics of HMR 3270, a glucan synthase inhibitor, in a murine candidiasis model. Antimicrob Agents Chemother 47: 1187–1192
Warn PA, Sharp A, Morrissey G, Denning DW (2005) Activity of aminocandin (IP960) compared with amphotericin B and fluconazole in a neutropenic murine model of disseminated infection caused by a fluconazole-resistant strain of Candida tropicalis. J Antimicrob Chemother 56: 590–593
Bruzzese T, Rimaroli C, Bonabello A, Ferrari E, Signorini M (1996) Amide derivatives of patricin A with potent antifungal activity. Eur J Med Chem 31: 965–972
Kantarcioglu AS, Yucel A, Vidotto V (2003) In vitro activity of a new polyene SPK-843 against Candida spp, Cryptococcus neoformans and Aspergillus spp clinical isolates. J Chemother 15: 296–298
Kasanah N, Hamann MT (2005) SPK-843 (Aparts/Kaken). Curr Opin Investig Drugs 6: 845–853
Kaken Pharmaceutical Annual Report (2006) Available at: http://www.kaken.co/jp
Aparts BV Web Site (2006) Available at http://www.apartsbv.com.
Kaufman TS, Rúveda EA (2005) The quest for quinine: Those who won the battles and those who won the war. Angew Chem Int Ed Engl 44: 854–885
Tan RX, Zheng WF, Tang HQ (1998) Biologically active substances from the genus Artemisia. Planta Med 64: 295–302
Newman JD, Marshall J, Chang M, Nowoozi F, Paradise E, Pitera D, Newman KL, Keasling JD (2006) High-level production of amorpha-4,11-diene in a two-phase partitioning bioreactor of metabolically engineered Escherichia coli. Biotecnol Bioeng 95: 684–691
Boatin BA, Richards FO Jr (2006) Control of onchoceriasis. Adv Parasitol 61: 349–394
Sanofi-Aventis Annual Report (2005) Available at http://www.sanofiaventis.com
Didier PJ, Phillips JN, Kuebler DJ, Nasr M, Brindley PJ, Stovall ME, Bowers LC, Didier ES (2006) Antimicrosporidial activities of fumagillin, TNP-470, ovalicin, and ovalicin derivatives in vitro and in vivo. Antimicrob Agents Chemother 50: 2146–2155
Didier ES (2005) Microsporidiosis: An emerging and opportunistic infection in humans and animals. Acta Trop 94: 61–76
Griffith EC, Su Z, Niwayama S, Ramsay CA, Chang YH, Liu JO (1998) Molecular recognition of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2. Proc Natl Acad Sci USA 95: 15183–15188
Upadhya R, Zhang HS, Weiss LM (2006) System for expression of microsporidian methionine amino peptidase type 2 (MetAP2) in the yeast Saccharomyces cerevisiae. Antimicrob Agents Chemother 50: 3389–3395
Peterson RT (2006) A noncanonical path to mechanism of action. Chem Biol 13: 924–926
Zhang Y, Yeh JR, Mara A, Ju R, Hines JF, Cirone P, Griesbach HL, Schneider I, Slusarski DC, Holley SA et al (2006) A chemical and genetic approach to the mode of action of fumagillin. Chem Biol 13: 1001–1009
Haynes RK (2006) From artemisinin to new artemisinin antimalarials: Biosynthesis, extraction, old and new derivatives, stereochemistry and medicinal chemistry requirements. Curr Top Med Chem 6: 509–537
Haynes RK, Fugmann B, Stetter J, Rieckmann K, Heilmann HD, Chan HW, Cheung MK, Lam WL, Wong HN, Croft SL et al (2006) Artemisone —a highly active antimalarial drug of the artemisinin class. Angew Chem Int Ed 45: 2082–2088
Eckstein-Ludwig U, Webb RJ, Van Goethem ID, East JM, Lee AG, Kimura M, O’Neill PM, Bray PG, Ward SA, Krishna S (2003) Artemisinins target the SERCA of Plasmodium falciparum. Nature 424: 957–961
Jambou R, Legrand E, Niang M, Khim N, Lim P, Volney B, Ekala MT, Bouchier C, Esterre P, Fandeur T et al (2005) Resistance of Plasmodium falciparum field isolates to in vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet 366: 1960–1963
Uhlemann AC, Cameron A, Eckstein-Ludwig U, Fischbarg J, Serovich P, Zuniga FA, East M, Lee A, Brady L, Haynes RK et al (2005) A single amino acid residue can determine the sensitivity of SERCAs to artemisinins. Nat Struct Mol Biol 12: 628–629
Golenser J, Waknine JH, Krugliak M, Hunt NH, Grau GE (2006) Current perspectives on the mechanism of action of artemisinins. Int J Parasitol 36: 1427–1441
Krishna S, Woodrow CJ, Staines HM, Haynes RK, Mercereau-Puijalon O (2006) Reevaluation of how artemisinins work in light of emerging evidence of in vitro resistance. Trends Mol Med 12: 200–205
Endo A (1975) Compactin (ML-236B) and related compounds as potential cholesterol-lowering agents that inhibit HMG-CoA reductase. J Med Chem 28: 401–405
Brown AG, Smale TC, King TJ, Hasenkamp R, Thompson RH (1976) Crystal and molecular structure of compactin, a new antifungal metabolite from Penicillium brevicompactum. J Chem Soc, Perkin Trans 1: 1165–1170
Endo A (1979) Monacolin K, a new hypocholesterolemic agent. J Antibiot 32: 852–854
Endo A (1980) Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. J Antibiot 33: 334–336
Vagelos RP (1991) Are prescription drug prices too high? Science 252: 1090–1084
Arcamone FM (2005) Anthracyclines. In: GM Cragg, DGI Kingston, DJ Newman (eds): Anticancer agents from natural products. Taylor and Francis, Boca Raton, FL, 299–320
Pommier Y (2006) Topoisomerase I inhibitors: Camptothecins and beyond. Nat Rev Cancer 6: 789–802
Hecht SM (2005) Bleomycin group antitumor agents. In: GM Cragg, DGI Kingston, DJ Newman (eds): Anticancer agents from natural products. Taylor and Francis, Boca Raton, FL, 357–381
Hamann PR, Upeslacis J, Borders DB (2005) Enediynes. In: GM Cragg, DGI Kingston, DJ Newman (eds): Anticancer agents from natural products. Taylor and Francis, Boca Raton, FL, 451–474
Hamann PR, Hinman LM, Hollander I, Beyer CF, Lindh D, Holocomb R, Hallett W, Tsou H-R, Upeslacis J, Shochat D et al (2002) Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Bioconjugate Chem 13: 47–58
Hartwell JL (1982) Plants used against cancer. Quarterman, Lawrence, MA
Cragg GM, Boyd MR, Cardellina II JH, Newman DJ, Snader KM, McCloud TG (1994) Ethnobotany and drug discovery: The experience of the US National Cancer Institute. In: DJ Chadwick, J Marsh (eds): Ethnobotany and the search for new drugs Ciba Foundation Symposium. Wiley & Sons, Chichester, UK, 178–196
Eyberger AL, Dondapati R, Porter JR (2006) Endophyte fungal isolates from Podophyllum peltatum produce podophyllotoxin. J Nat Prod 69: 1121–1124
Kingston DGI (2005) Taxol and its analogs. In: GM Cragg, DGI Kingston, DJ Newman (eds): Anticancer agents from natural products. Taylor and Francis, Boca Raton, FL, 89–122
Desai N, Trieu V, Yao Z, Louie L, Ci S, Yang A, Tao C, De T, Beals B, Dykes D et al (2006) Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of Cremophor-free, albumin-bound paclitaxel, ABI-007, compared with Cremophor-based paclitaxel. Clin Cancer Res 12: 1317–1324
Green MR, Manikhas GM, Orlov S, Afanasyev B, Makhson AM, Bhar P, Hawkins MJ (2006) Abraxane®, a novel Cremophor®-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Ann Oncol 17: 1263–1268
Rahier NJ, Thomas J, Hecht SM (2005) Camptothecin and its analogs. In: GM Cragg, DGI Kingston, DJ Newman (eds): Anticancer agents from natural products. Taylor and Francis, Boca Raton, FL, 5–21
Lee JH, Lee JM, Kim JK, Ahn SK, Lee SJ, Kim MY, Jew SS, Park JG, Hong CI (1998) Antitumor activity of 7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, CKD602, as a potent DNA topoisomerase I inhibitor. Arch Pharm Res 21: 581–590
Chung MK, Han SS, Kim JC (2006) Evaluation of the toxic potentials of a new camptothecin anticancer agent CKD-602 on fertility and early embryonic development in rats. Regul Toxicol Pharmacol 45: 273–281
Crul M (2003) CKD-602. Chong Kun Dang. Curr Opin Investig Drugs 4: 1455–1459
Ishizumi K, Ohashi N, Tanno N (1987) Stereospecific total synthesis of 9-aminoanthracyclines: (+)-9-amino-9-deoxydaunomycin and related compound. J Org Chem 52: 4477–4485
Hanada M, Mizuno S, Fukushima A, Saito Y, Noguchi T, Yamaoka T (1998) A new antitumor agent amrubicin induces cell growth inhibition by stabilizing topoisomerase II-DNA complex. Jpn J Cancer Res 89: 1229–1238
Hanada M, Noguchi T, Yamaoka T (2006) Amrubicin induces apoptosis in human tumor cells mediated by the activation of caspase-3/7 preceding a loss of mitochondrial membrane potential. Cancer Sci 97: 1396–1403
Miller TA, Witter DJ, Belvedere S (2003) Histone deacetylase inhibitors. J Med Chem 46: 5097–5116
Richon VM, Webb Y, Merger R, Sheppard T, Jursic B, Ngo L, Civoli F, Breslow R, Rifkind RA, Marks PA (1996) Second generation hybrid polar compounds are potent inducers of transformed cell differentiation. Proc Natl Acad Sci USA 93: 5705–5708
Bolden JE, Peart MJ, Johnstone RW (2006) Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5: 769–784
Tsuji N, Kobayashi M, Nagashima K, Wakisaka Y, Koizumi K (1976) A new antifungal antibiotic, trichostatin. J Antibiot 29: 1–6
Yoshida M, Kijima M, Akita M, Beppu T (1990) Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 265: 17174–17179
Gu J, Ruppen ME, Cai P (2005) Lipase-catalyzed regioselective esterification of rapamycin: Synthesis of temsirolimus (CCI-779). Org Lett 7: 3945–3948
Reddy GK, Mughal TI, Rini BI (2006) Current data with mammalian target of rapamycin inhibitors in advanced-stage renal cell carcinoma. Clin Genitourin Cancer 5:110–113
Smolewski P (2006) Investigating mammalian target of rapamycin inhibitors for their anticancer properties. Expert Opin Investig Drugs 15: 1201–1227
Jimeno J, Faircloth G, Fernández-Sousa JM, Scheuer P, Rinehart K (2004) New marine derived anticancer therapeutics —A journey from the sea to clinical trials. Mar Drugs 2: 14–29
Fayette J, Coquard IR, Alberti L, Boyle H, Meeus P, Decouvelaere AV, Thiesse P, Sunyach MP, Ranchere D, Blay JY (2006) ET-743: A novel agent with activity in soft-tissue sarcomas. Curr Opin Oncol 18: 347–353
Sakai R, Rinehart KL, Guan Y, Wang AH (1992) Additional antitumor ecteinascidins from a Caribbean tunicate: Crystal structures and activities in vivo. Proc Natl Acad Sci USA 89: 11456–11460
Sakai R, Jares-Erijman EA, Manzanares I, Silva Elipe MV, Rinehart KL (1996) Ecteinascidins: Putative biosynthetic precursors and absolute stereochemistry. J Am Chem Soc 118: 9017–9023
Menchaca R, Martinez V, Rodriguez A, Rodriguez N, Flores M, Gallego P, Manzanares I, Cuevas C (2003) Synthesis of natural ecteinascidins (ET-729, ET-745, ET-759B, ET-736, ET-637, ET-594) from cyanosafracin B. J Org Chem 68: 8859–8866
David-Cordonnier MH, Gajate C, Olmea O, Laine W, de la Iglesia-Vicente J, Perez C, Cuevas C, Otero G, Manzanares I, Bailly C et al (2005) DNA and non-DNA targets in the mechanism of action of the antitumor drug trabectedin. Chem Biol 12: 1201–1210
Pettit GR, Singh SB, Hamel E, Lin CM, Alberts DS, Garcia-Kendall D (1989) Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4. Experientia 45: 209–211
Pettit GR, Singh SB, Hamel E, Lin CM, Alberts DS, Garcia-Kendall D (1989) Erratum, isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4. Experientia 45: 680
Chaplin DJ, Horsman MR, Siemann DW (2006) Current development status of smallmolecule vascular disrupting agents. Curr Opin Investig Drugs 7: 522–528
Mahindroo N, Liou J-P, Chang J-Y, Hsieh H-P (2006) Antitubulin agents for the treatment of cancer —a medicinal chemistry update. Expert Opin Ther Patents 16: 647–691
Tron GC, Pirali T, Sorba G, Pagliai F, Busacca S, Genazzani AA (2006) Medicinal chemistry of combretastatin A4: Present and future directions. J Med Chem 49: 3033–3044
Pettit GR, Temple Jr C, Narayanan VL, Varma R, Simpson MJ, Boyd MR, Rener GA, Bansal N (1995) Antineoplastic agents 322. Synthesis of combretastatin A-4 prodrugs. Anticancer Drug Des 10: 299–309
Tujebajeva RM, Graifer DM, Karpova GG, Ajtkhozhina NA (1989) Alkaloid homoharringtonine inhibits polypeptide chain elongation on human ribosomes on the step of peptide bond formation. FEBS Lett 257: 254–256
Kantarjian HM, Talpaz M, Santini V, Murgo A, Cheson B, O’Brien SM (2001) Homoharringtonine: history, current research, and future direction. Cancer 92: 1591–1605
Lévy V, Zohar S, Bardin C, Vekhoff A, Chaoui D, Rio B, Legrand O, Sentenac S, Rousselot P, Raffoux E et al (2006) A phase I dose-finding and pharmacokinetic study of subcutaneous semisynthetic homoharringtonine (ssHHT) in patients with advanced acute myeloid leukaemia. Br J Cancer 95: 253–259
Powell RG, Weisleder D, Smith Jr CR, Rohwedder WK (1970) Structures of harringtonine, isoharringtonine, and homoharringtonine. Tetrahedron Lett 11: 815–818
Robin J-P, Blanchard J, Cavoleau S, Chauviat L, Charbonnel S, Dhal R, Dujardin G, Fournier F, Gilet C, Girodier L et al (2001) USA Patent No. US6,613,900
Choueiri TK, Wesolowski R, Mekhail TM (2006) Phenoxodiol: Isoflavone analog with antineoplastic activity. Curr Oncol Rep 8: 104–107
Mor G, Fu HH, Alvero AB (2006) Phenoxodiol, a novel approach for the treatment of ovarian cancer. Curr Opin Investig Drugs 7: 542–548
Davies SL, Bozzo J (2006) Spotlight on tNOX: A tumor-selective target for cancer therapies. Drug News Perspect 19: 223–225
Gelmon KA, Latreille J, Tolcher A, Génier L, Fisher B, Forand D, D’Aloisio S, Vernillet L, Daigneault L, Lebecq A et al (2000) Phase I dose-finding study of a new taxane, RPR 109881A, administered as a one-hour intravenous infusion days 1 and 8 to patients with advanced solid tumors. J Clin Oncol 18: 4098–4108
Kurata T, Shimada Y, Tamura T, Yamamoto N, Hyodo I, Saeki T, Takashima S, Fujiwara K, Wakasugi H, Kashimura M (2000) Phase I and pharmacokinetic study of a new taxoid, RPR 109881A, given as a 1-hour intravenous infusion in patients with advanced solid tumors. J Clin Oncol 18: 3164–3171
Sessa C, Cuvier C, Caldiera S, Bauer J, Van den Bosch S, Monnerat C, Semiond D, Pérard D, Lebecq A, Besenval M et al (2002) Phase I clinical and pharmacokinetic studies of the taxoid derivative RPR 109881A administered as a 1-hour or a 3-hour infusion in patients with advanced solid tumors. Ann Oncol 13: 1140–1150
Kaur G, Stetler-Stevenson M, Sebers S, Worland P, Sedlacek H, Myers C, Czech J, Naik R, Sausville E (1992) Growth inhibition with reversible cell cycle arrest of carcinoma cells by flavone L86-8275. J Natl Cancer Inst 84: 1736–1740
Blagosklonny MV (2004) Flavopiridol, an inhibitor of transcription: implications, problems and solutions. Cell Cycle 3: 1537–1542
Potapova TA, Daum JR, Pittman BD, Hudson JR, Jones TN, Satinover DL, Stukenberg PT, Gorbsky GJ (2006) The reversibility of mitotic exit in vertebrate cells. Nature 440: 954–958
Shapiro GI (2006) Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 24: 1770–1783
Harmon AD, Weiss U, Silverton JV (1979) The structure of rohitukine, the main alkaloid of Amoora rohituka (Syn. Aphanamixis polystachya) (Meliaceae). Tet Letts 20: 721–724
Naik RG, Kattige SL, Bhat SB, Alreja B, de Souza NJ, Rupp RH (1988) An antiinflammatory cum immunomodulatory piperidinylbenzopyranone from Dysoxylum binectariferum: Isolation, structure and total synthesis. Tetrahedron 44: 2081–2086
Bennouna J, Campone M, Delord JP, Pinel MC (2005) Vinflunine: A novel antitubulin agent in solid malignancies. Expert Opin Investig Drugs 14: 1259–1267
Kruczynski A, Poli M, Dossi R, Chazottes E, Berrichon G, Ricome C, Giavazzi R, Hill BT, Taraboletti G (2006) Anti-angiogenic, vascular-disrupting and anti-metastatic activities of vinflunine, the latest vinca alkaloid in clinical development. Eur J Cancer 42: 2821–2832
Johnson SAN (1996) Vinorelbine: An update and review of activity. Clin Oncol 8: 353–357
Fahy J, Duflos A, Ribet J-P, Jacquesy J-C, Berrier C, Jouannetaud M-P, Zunino F (1997) Vinca alkaloids in superacidic media: A method for creating a new family of antitumor derivatives. J Am Chem Soc 119: 8576–8577
Jacquesy J-C, Berrier C, Jouannetaud M-P, Zunino F, Fahy J, Duflos A, Ribet J-P (2002) Fluorination in superacids: A novel access to biologically active compounds. J Fluor Chem 114: 139–141
Okouneva T, Hill BT, Wilson L, Jordan MA (2003) The effects of vinflunine, vinorelbine, and vinblastine on centromere dynamics. Mol Cancer Ther 2: 427–436
Nettleton DE, Doyle TW, Krishnan B, Matsumoto GK, Clardy J (1985) Isolation and structure of rebeccamycin —a new antitumor antibiotic from Nocardia aerocoligenes. Tetrahedron Lett 26: 4011–4014
Krishnan BS, Moore ME, Lavoie CP, Long BH, Dalterio RA, Wong HS, Rosenberg IE (1994) Fluorescence polarization studies of the binding of BMS 181176 to DNA. J Biomol Struct Dyn 12: 625–636
Long BH, Rose WC, Vyas DM, Matson JA, Forenza S (2002) Discovery of antitumor indolocarbazoles: Rebeccamycin, NSC 655649, and fluoroindolocarbazoles. Curr Med Chem Anticancer Agents 2: 255–266
Prudhomme M (2003) Rebeccamycin analogues as anti-cancer agents. Eur J Med Chem 38: 123–140
Rewcastle GW (2005) Becatecarin (Helsinn Healthcare). IDrugs 8: 838–847
Ricart AD, Hammond LA, Kuhn JG, Takimoto CH, Goetz A, Forouzesh B, Forero L, Ochoa-Bayona JL, Berg K, Tolcher AW et al (2005) Phase I and pharmacokinetic study of sequences of the rebeccamycin analogue NSC 655649 and cisplatin in patients with advanced solid tumors. Clin Cancer Res 11: 8728–8736
Faul MM, Gillig JR, Jirousek MR, Ballas LM, Schotten T, Kahl A, Mohr M (2003) Acyclic N-(azacycloalkyl)bisindolylmaleimides: Isozyme selective inhibitors of PKCβ. Bioorg Med Chem Lett 13: 1857–1859
Faul MM, Grutsch JL, Kobierski ME, Kopach ME, Krumrich CA, Staszak MA, Udodong U, Vicenzi JT, Sullivan KA (2003) Strategies for the synthesis of N-(azacycloalkyl)bisin dolylmaleimides: Selective inhibitors of PKCβ. Tetrahedron 59: 7215–7229
Pearce HL, Miller MA (2005) The evolution of cancer research and drug discovery at Lilly Research Laboratories. Adv Enzyme Regul 45: 229–255
Rizvi MA, Ghias K, Davies KM, Ma C, Weinberg F, Munshi HG, Krett NL, Rosen ST (2006) Enzastaurin (LY317615), a protein kinase Cβ inhibitor, inhibits the AKT pathway and induces apoptosis in multiple myeloma cell lines. Mol Cancer Ther 5: 1783–1789
Verhoef C, de Wilt JH, Verheul HM (2006) Angiogenesis inhibitors: Perspectives for medical, surgical and radiation oncology. Curr Pharm Des 12: 2623–2630
Altmann K-H (2004) The merger of natural product synthesis and medicinal chemistry: On the chemistry and chemical biology of epothilones. Org Biomol Chem 2: 2137–2152
Bergstralh DT, Ting JP (2006) Microtubule stabilizing agents: Their molecular signaling consequences and the potential for enhancement by drug combination. Cancer Treat Rev 32: 166–179
Höfle G, Bedorf N, Gerth K, Reichenbach H (1993) German Patent No. DE4,138,042
Höfle G, Bedorf N, Steinmetz H, Schomburg D, Gerth K, Reichenbach H (1996) Epothilone A and B —novel 16-membered. Macrolides with cytotoxic activity: Isolation, crystal structure, and conformation in solution. Angew Chem Int Ed 35: 1567–1569
Gerth K, Bedorf N, Höfle G, Irschik H, Reichenbach H (1996) Epothilons A and B: Antifungal and cytotoxic compounds from Sorangium cellulosum (Myxobacteria). Production, physico-chemical and biological properties. J Antibiot 49: 560–563
Bollag DM, McQueney PA, Zhu J, Hensens O, Koupal L, Liesch J, Goetz M, Lazarides E, Woods CM (1995) Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res 55: 2325–2333
Rubin EH, Rothermel J, Tesfaye F, Chen T, Hubert M, Ho YY, Hsu CH, Oza AM (2005) Phase I dose-finding study of weekly single-agent patupilone in patients with advanced solid tumors. J Clin Oncol 23: 9120–9129
Borzilleri RM, Zheng X, Schmidt RJ, Johnson JA, Kim SH, DiMarco JD, Fairchild CR, Gougoutas JZ, Lee FYF, Long BH et al (2000) A novel application of a Pd(0)-catalyzed nucleophilic substitution reaction to the regioand stereoselective synthesis of lactam analogues of the epothilone natural products. J Am Chem Soc 122: 8890–8897
Lee FYF, Borzilleri R, Fairchild CR, Kim SH, Long BH, Reventos-Suarez C, Vite GD, Rose WC, Kramer RA (2001) BMS-247550: A novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy. Clin Cancer Res 7: 1429–1437
Puri SC, Verma V, Amna T, Qazi N, Spiteller M (2005) An endophytic fungus from Nothapodytes foetida that produces camptothecin. J Nat Prod 68: 1717–1719
Yu T-W, Floss HG (2005) Ansamitocins (Maytansinoids). In: GM Cragg, DGI Kingston, DJ Newman (eds): Anticancer agents from natural sources. Taylor and Francis, Boca Raton, FL, 321–337
McAlpine JB, Bachmann BO, Piraee M, Tremblay S, Alarco A-M (2005) Microbial genomics as a guide to drug discovery and structural elucidation: ECO-02301, a novel anitfungal agent, as an example. J Nat Prod 68: 493–496
Challis GL, Hopwodd DA (2003) Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species. Proc Natl Acad Sci USA 100: 14555–14561
Newman DJ, Hill RT (2006) New drugs from marine microbes: The tide is turning. J Ind Microbiol Biotechnol 33: 539–544
Partida-Martinez LP, Hertweck C (2005) Pathogenic fungus harbours endosymbiotic bacteria for toxin production. Nature 437: 884–888
Bok JW, Hiffmeister D, Maggio-Hall LA, Murillo R, Glasner JD, Keller NP (2006) Genomic mining for Aspergillus natural products. Chem Biol 13: 31–37
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Butler, M.S., Newman, D.J. (2008). Mother Nature’s gifts to diseases of man: the impact of natural products on anti-infective, anticholestemics and anticancer drug discovery. In: Petersen, F., Amstutz, R. (eds) Natural Compounds as Drugs Volume I. Progress in Drug Research, vol 65. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8117-2_1
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