Section Review: Anti-infectives: Lipopeptide antifungal agents

References

• WALSH TJ, JAROSINSKI PF, FROMTLING RA: Increasing usage of systemic antifungal agents. Diagn. Infect. Dis. (1990) 13:37–40.
   PubMed Web of Science ®Google Scholar
• GRAYBILL JR: Future directions of antifungal chemo-therapy. Clin. Infect. Dis. (1992) 14 (Suppl. 1): S170–181.
   Google Scholar
• POLAK A, HARTMAN PG: Antifungal chemotherapy - are we winning? In: Progress in Drug Research (1991) 37:181-269. Jucker E (Ed), Birkhauser Verlag, Basel.
   Google Scholar
• SALONEN J, NIKOSKELAINEN J: Lethal infections in pa-tients with hematological malignancies. Eur. J. Haema-tot (1993) 51:102–108.
   PubMed Web of Science ®Google Scholar
• PAYA CV: Fungal infections In solid-organ transplanta-tion. Clin. Infect. Dis. (1993) 16:677–688.
   PubMed Web of Science ®Google Scholar
• SARAL R: Candida and Aspergillus infections in immu-nocompromised patients - an overview. Rev. Infect. Dis. (1991) 13:487–492.
   PubMedGoogle Scholar
• MILT S J, MASUR H: AIDS-related infections. ScientificAmerican (1990) August:50–57.
   Google Scholar
• LYMAN CA, WALSH TJ: Systemically administered anti-fungal agents. A review of their clinical pharmacology and therapeutic applications. Drugs (1992) 44:9–35.
   Google Scholar
• An excellent review of current antifungal agents useful for systemic infection and of experimental agents in development. The review covers the polyenes, flucytosine, azoles and other investigational compounds.
   Google Scholar
• BAILEY EM, KRAKOVSICY DJ, RYBAK MJ: The triazoleantifungal agents: A review of itraconazole and flucona-zole. Pharmacother. (1990) 10:146–153.
   PubMed Web of Science ®Google Scholar
• GALLIS HA, DREW RH, PICKARD WW: Amphotericki B: 30years of clinical experience. Rev. Infect. Dis. (1990) 12:308–329.
   PubMedGoogle Scholar
• COUROUX P, SCHIEVEN BC, HUSSAIN Z: Pneumocystiscarinii. ASM News (1993) 59:179–181.
   Google Scholar
• PERFECT JR: Antifungal prophylaxis - to prevent or not. Am. J. Med. (1993) 94:233–234.
   PubMed Web of Science ®Google Scholar
• SANGUINETI A, CARMICHAEL JK, CAMPBELL K: Flucona-zole-resistant Candida albicans after long-term sup-pressive therapy. Archives of Internal Medicine (1993) 153:1122–1124.
   PubMed Web of Science ®Google Scholar
• KITCHEN VS, SAVAGE M, HARRIS JRW: Candida-albicansresistance in AIDS. J. Infect. (1991) 22:204–205.
   PubMed Web of Science ®Google Scholar
• FOX R, NEAL KR, LEEN CLS, ELLIS ME, MANDAL BK: Fluconazole resistant Candida in AIDS. J. Infect. (1991) 22:201–204.
   PubMed Web of Science ®Google Scholar
• WINGARD JR, MERZ WG, RINALDI MG, MILLER CB, KARPJE, SARAL R: Association of Torulopsis-glabrata infec-tions with fluconazole prophybiris in neutropenic bone marrow transplant patients. Antimicivb. Agents Chemother. (1993) 37:1847–1849.
   PubMed Web of Science ®Google Scholar
• HITCHCOCK CA, PYE GW, TROKE PF, JOHNSON EM, WARNOCK DW: Fluconazole resistance in Candida-glabrata. Antimicrob. Agents Chemother. (1993) 37:1962–1965.
   PubMed Web of Science ®Google Scholar
• MEIS JF, DONNELLY JP, HOOGKAMP-KORSTANJE JA, DEPAUW BE: Aspergillus-fumigatis pneumonia in ne-tropenic patients during therapy with fluconazole for infection due to Candida species. din, Inf. Dis. (1993) 16:734–735.
   Web of Science ®Google Scholar
• CLARK AM: The need for new antifungal drugs. In: New Approaches ForAntifungalDrugs(1992). Femandes, BP (Ed), Birkhauser, Boston.
   Google Scholar
• TKACZ JS: Glucan biosynthesis in fungi and its inhibi- tion. In: Emerging Targets In Antibacterial And Antifungal Chemotherapy (1992). Sutcliffe J, Georgopapadakou NH (Eds), Chapman and Hall, New York.
   Google Scholar
• A good review of glucan biosynthesis and antifungal agents inhibit-ing this target.
   Google Scholar
• RUIZ-HERRERA J: Biosynthesis of I3-glucans in fungi. Antonie van Leewenhoek (1991) 60:73-81. A good review of glucan biosynthesis.
   Google Scholar
• SHEPHERD MG, GOPAL PK: Candida albicans: Cell wall physiology and metabolism. In: Candida and Candi-damycosis (1991). Tumbay E (Ed), Plenum Press, New York.
   Google Scholar
• MIZOGUCHI J, SAITO T, MIZUNO K, HAYANO K: On the mode of action of a new antifungal antibiotic, aculeacin A: Inhibition of cell wall synthesis in Saccbaromyces cerevisiae. J. Antibiot. (1977) 30:308–313.
   PubMed Web of Science ®Google Scholar
• SMULIAN AG, WALZER PD: The biology of Pneumocystis carinii. Crit. Rev. Microbiol. (1992) 18:191–216.
   PubMed Web of Science ®Google Scholar
• An updated review of the biology of P. carinii.
   Google Scholar
• MATSUMOTO Y, MATSUDA S, TEGOSHI T: Yeast glucan In the cyst wall of Pneumocystis carinii. j Protozool. (1989) 36:21S.
   PubMedGoogle Scholar
• This disclosure was the first that indicated the cyst wall of P. carinii contained 13-(l,3)-glucan.
   Google Scholar
• HRMOVA M, TAFT CS, SELMIENNIKOFF CP: 1,3-13-Glucan synthase of Neurospora-crassa: Partial purification and characterization of solubilized enzyme activity. Exper. MycoL (1989) 13:129–139.
   Google Scholar
• FROST DJ, DRAKE RR, WASSERMAN BP: (1,3)-13-Glucansynthase from Saccbaromyces cerevisiae In vitro acti-vation by 13-lactoglobulin or Brll-35, and photoaffinity labeling of enriched microsomal fractions with 5-azido-UDP-Glc and 8-aziclo-GTP. Curr. Microbiol. (1992) 24:295–300.
   Web of Science ®Google Scholar
• AWALD P, ZUGEL M, MONKS C, FROST D, SELITRENNIK- OFF CP: Purification of 1,3-13-glucan synthase fromNeurospora-crassa by product entrapment. Exper. My-col. (1993) 17:130–141.
   Google Scholar
• A highly purified fungal glucan synthase enzyme is reported.
   Google Scholar
• TAFT CS, SELITRENNIKOFF CP: Cilofungin inhibition of (1,3)-0-glucan synthase: The lipophilic side chain is essential for inhibition of enzyme activity. J. Antibiot. (1990) 43:433–437.
   PubMed Web of Science ®Google Scholar
• HAMMOND ML: Chemical and structure-activity studies of the echkkocandin lipopeptides. In: Cutaneous Antifun-gal Agents (1993). Rippon JW, Fromtling RA (Eds), Marcel Dekker, New York.
   Google Scholar
• A detailed account of the discovery, and isolation of the echino-candin, aculeacin, sporiofungin, mulundocandin, and pneumocandin natural products with emphasis on chemical and structure-activity aspects.
   Google Scholar
• SCHMATZ DM: The use of 13–1,3-glucan synthesis Inhibi-tors for the treatment and prevention of Pneumocystis carinii pneumonia. In: Pneumocystis carinii (1994). Walzer PD (Ed), Marcel Dekker, New York.
   Google Scholar
• A good review with a brief history of 0-(1,3)-glucan synthesis inhibitors, mechanism of action and use as anti-Pneumocystis agents.
   Google Scholar
• HENSENS OD, LLESCH JM, ZINK DL, SMITH JL, \WICHMANNCF, SCHWARTZ RE: Pneumocandins from Zalerton ar-boricola 111. Structure elucidation. J. Antibiot. (1992) 45:1875–1885.
   PubMed Web of Science ®Google Scholar
• BENZ F. KNUSEL F, NUESCH J, TREICHLER H, VOSER W, NYFELER R, KELLER-SCHIERLEIN W: Stoffwechselpro-dukte von mikroorganismen. Echinocandin B, emn neuartiges polypeptid-antibioticutn am Aspergillus nidulans var. ecbinulatus: isolierung und bausteine. Hely. Chim. Ada (1974) 57:2459–2477.
   Google Scholar
• The first account of the echinocandin class of lipopeptides.
   Google Scholar
• KEIJER-JUSLEN C, KUHN M, LOOSLI H-R, PECHTER TJ, WEBER HP, WARTBURG A: Struktur des cyclopeptid-an-tibiotilcums SL 7810 (= echinocandin B). Tetrahedron Lett. (1976) 4147–4150.
   Google Scholar
• Describes the structure determination, and crystal structure of echi-nocandin B and several heavy-atom derivatives.
   Google Scholar
• TRABER R, KELLER-JUSLEN C, LOOSLI H-R, KUHN M, WAR- TBURG A: Cyclopeptid-antibiotika aus AspergiUus-arten. Struktur der echinocandine C und D. Helv. Chim. Acta (1979) 62:1252–1267.
   Google Scholar
• This paper gives a full account of the isolation, and structure determination of echinocandins B, C and D.
   Google Scholar
• MIZUNO K, YAGI A, SATOI S, TAKADA M, HAYASHI M,ASANO K, MATSUDA T: Studies on acukacin. I. Isolation and characterization of acukacin A. J. Antibiot. (1977) 30:297–302.
   PubMed Web of Science ®Google Scholar
• IWATA K, YAGI A, SATOI S, TAKADA M, HAYASHI M, ASANO K, MATSUDA T: In vitro studies of ackdeacin A, a new antifungal antibiotic. J Antibiot. (1977) 30:203–209.
   Google Scholar
• SATOI S, YAGI A, ASANO K, MIZUNO K, WATANABE T:Studies on aculeacin. II. Isolation and characterization of aculeacins B, C, D, E, F and G. J. Antibiot. (1977) 30:303–307.
   Google Scholar
• Describes the isolation and in vitro activity of the minor aculeacins. The structures of aculeacins B-G have not been fully determined.
   Google Scholar
• YAMAGUCHI H, HIRITANI T, 1WATA K, YAMAMOTO Y: Studies on the mechanism of action of acukacin A. J. Antibiot. (1982) 35:210–219.
   PubMed Web of Science ®Google Scholar
• SAWISTOWSKA-SCHRODER ET, KERRIDGE D, PERRY H:Echinocandin inhibition of 1,3-13-D-g1ucan synthase from Candida albicans. FESS Lett. (1984) 173:134–138.
   PubMed Web of Science ®Google Scholar
• TAFT CS, STARK T, SELITRENNIKOFF CP: Cilofungin (LY121019) inhibits Candida albicans (1,3)41-D-glucan synthase activity. Antimicrob. Agents Chemother. (1988) 32:1901–1903.
   PubMed Web of Science ®Google Scholar
• TANG J, PARR TR: W-1 Solubilization and kinetics of inhibition by cilofungin of Candida albicans glucan synthase. Antimicrob. Agents Chemother. (1991) 35:99–103.
   PubMed Web of Science ®Google Scholar
• The first solubilization of the Candida glucan synthase enzyme.
   Google Scholar
• BEAULIEU D, TANG J, ZECKNER DJ, PARR Jr TR: Correla-tion of cilofunginin vivo efficacy with its activity against Aspergillus fumigatus (1,3)-0-D-glucan synthase. FEMS Micro biol. Len. (1993) 108:133–138.
   PubMed Web of Science ®Google Scholar
• FONT DE MORA J, HERRERO E, SENTANDREU R: A kinetic study on the regeneration of Candida albicans proto-plasts in the presence of cell wall synthesis inhibitors. FEMS Micro biol. Lett. (1993) 108:43–48.
   PubMedGoogle Scholar
• Study shows that glucans are still formed in the presence of 3-(1,3)-glucan synthesis inhibitors, but the glucan is no longer cell wall bound.
   Google Scholar
• BARTIZAL K, ABRUZZO GK, SCHMATZ DM: Biological activity of the pneumocandins. In: Cutaneous AnttfungalAgents (1993). Rippon JW, Fromtling RA (Eds), Marcel Dek-ker, New York.
   Google Scholar
• A detailed account of the biological activity of the pneumocandin natural products. Comparisons between these and echinocandins B and C, tetrahydroechinocandins B and C, cilofungin and am-photericin B is made.
   Google Scholar
• PACHE W, KELLER C, KUHN M: Cleavage of echinocandin B with polymyxin acylase liberating the fatty acid and reacylation of the peptide moiety. Experientia (1978) 34:1670–1671.
   Google Scholar
• KIMURA Y, YASUDA N: Polymyxin acylase: purificationand characterization, with special reference to broad substrate specificity. Agric. Biol. Chem. (1989) 53:497–504.
   Web of Science ®Google Scholar
• BOECK ID, FUKUDA DS, ABBOTT BJ, DEBONO M: Deacy-lation of echinocandin B by Actinoplanes utabensis. I Antibiot. (1989) 42:382.
   Google Scholar
• TAKESHIMA H, INOKOSHI J, TAKEDA Y, TANAKA H, OMURA S: A deacylation enzyme for aculeacin A, a neutral lipophilic antibiotic, fromActinoplanesutaben-sis: purification and characterization./ Biochem. (1989) 105:606–610.
   Web of Science ®Google Scholar
• INOKOSHI J, TAKESHIMA H, IKEDA H, OMURA S: Cloning and sequencing of the acukacin-A acylase-encoding gene from Acinoplanes utabensis and expression in Streptotnyces lividans. Gene (1992) 119:29–35.
   PubMed Web of Science ®Google Scholar
• Aculeacin A acylase is apparently the same enzyme described by Lilly for the deacylation of echinocandin B.
   Google Scholar
• INOKOSHI J, TAKESHIMA H, IKEDA H, OMURA S: Efficient production of acukacin A acylase in recombinant Streptomyces strains. Appl. Micro biol. Biotechnol. (1993) 39:532–536.
   Web of Science ®Google Scholar
• DEBONO M, ABBOTT BJ, TURNER JR, HOWARD LC, GOR-DEE RS, HUNT AS, BARNHART M, MOLLOY RM, VUILLARD ICE, FUKUDA D, BUTLER TF, ZECKNER DJ: Synthesis and evaluation of LY121019, a member of a series of semi-synthetic analogues of the antifungal lipopeptide echi-nocandin B. Ann, N.Y. Acad. Sci. (1988) 544:152–167.
   PubMedGoogle Scholar
• The full account and structure-activity studies of side chain analogues of echinocandin B by the Lilly group. The choice of cilofungin (LY121019) as a candidate for further study was discussed.
   Google Scholar
• DEBONO M, ABBOTT BJ, FUKUDA DS, BARNHART M, WILLARD ICE, MOLLOY RM, MICHEL ICII, TURNER JR, BUTLER TF, HUNT AH: Synthesis of new analogs of echinocandin B by enzymatic deacylation and chemical reacylation of the echinocandin B peptide: synthesis of the antifungal agent cilofungin (LY121019). J. Antibiot. (1989) 42:389–397.
   PubMed Web of Science ®Google Scholar
• Describes the synthesis and physicochemical properties of cilo-fungin.
   Google Scholar
• GORDEE RS, ZECKNER DJ, ELLIS LF, THAIUCAR AL, HOWARD LC: In vitro and in vivo anti-Candida activityand toxicology of LY121019. J. Antibiot. (1984) 37:1054–1065.
   PubMed Web of Science ®Google Scholar
• Contains a full description of activity, and toxicology results with cilofungin and several side chain analogues.
   Google Scholar
• GORDEE RS, ZECKNER DJ, HOWARD LC, ALBORN WE, DEBONO M: Anti-Candida activity and toxicology of LY121019, a novel semisynthetic polypeptide antifun- gal antibiotic. Ann. N.Y. Acad. Sci. (1988) 544:294-301. The activity and toxicity of cilofungin is presented.
   Google Scholar
• DENNING DW, STEVENS DA: Efficacy of cilofungin alone and in combination with amphotericin B in a murine model of disseminated aspergillosis. Antimicrob. Agents Chemother. (1991) 35:1329–1333.
   PubMed Web of Science ®Google Scholar
• Cilofungin prolonged survival in this A. fumigatus mouse model at 62.5 mg/kg/day (:p, bid for eleven days) comparable in efficacy to amphotericin B given at 3.3 mg/kg/day (six total doses over eleven days).
   Google Scholar
• SCHMATZ DM, ROMANCHECK MA, PITTARELLI LA, SCHWARTZ RE, ROMTLING RA NOLLSTADT KIT, VANMID-DLESWORTH FL, WILSON ICE, TURNER MJ: Treatment of Pneumocystis carinii pneumonia with 1,3-(3-glucan synthesis inhibitors. .Pc. Natl. Acad. Sci. USA (1990) 87:5950–5954.
   PubMed Web of Science ®Google Scholar
• First account of the use of a 3-(1,3)-glucan synthesis inhibitor as an effective treatment for experimental P. carinii pneumonia.
   Google Scholar
• MATSUMOTO Y, YAMADA M, AMAGAI T: Yeast glucan of Pneumocystis carinii cyst wall: An excellent target for chemotherapy. J. Protozool. (1991) 38:6S–7S.
   Google Scholar
• Aculeacin A was efficacious at 2 or 10 mg/kg qd for two weeks in a rat P. carinii pneumonia model.
   Google Scholar
• KHARDORI N, NGUYEN H, STEPHENS LC, KALVAKUNTLA L, ROSENBAUM B, BODEY GP: Comparative efficacies of cilofungin (Ly121019) and amphotericin B against dis-seminated Candida albicans infection in normal and granulocytopenic mice. Antimicrob. Agents Chemother. (1993) 37:729–736•
   Google Scholar
• A study comparing survival and kidney clearance in normal and granulocytopenic mice with cilofungin and amphotericin B. Drugs were administered ip. Cilofungin dosed bid at 15–25 mg/kg/day for ten days was equivalent to or better than amphotericin dosed qd at 1 mg/kg /day.
   Google Scholar
• ROUSE MS, TALLAN BM, STECKELBERG JM, HENRY NK, WILSON WR: Efficacy of cilofimgin therapy adminis-tered by continuous intravenous infusion for experi-mental disseminated candidiasis in rabbits. Antimicrob. Agents Chemother. (1992) 36:56–58.
   PubMed Web of Science ®Google Scholar
• WALSH TJ, LEE JW, KELLY P, BACHER J, LECCIONES J, THOMAS V, LYMAN C, COLEMAN D, GORDEE R, PIZZO PA: Antifungal effects of the nonlinear pharmacokinetics of cilofungin, a 1,341-ghwan synthetase inhibitor, dur-ing continuous and intermittent intravenous infusions In treatment of experimental disseminated candidias is. Antimicrob. Agents Chemother. (1991) 35:1321–1328.
   PubMed Web of Science ®Google Scholar
• Cilofungin displays non-linear saturable plasma pharmacokinetics Doubling of dosage produced tissue levels ten-fold higher with an antibiotic effect 102 to 104 greater.
   Google Scholar
• SCHMATZ DM, FOWLES MA, MCFADDEN DC, PITTARELLI L, BALKOVEC J, HAMMOND M, ZAMBIAS R, LIBERATOR P, ANDERSON J: Antipneumocystis activity of water-sol-uble lipopeptide L-693,989 in rats. Antimicrob. Agents Chemother. (1992) 36:1964–1970.
   PubMed Web of Science ®Google Scholar
• Full account of the activity of L-693,989 in rat PCP model.
   Google Scholar
• BLACK HR, BRIER GL, WOLNY JD, DORRBECKER SH: Pharmacology and pharmacokinetics of cilofungin. Program and Abstracts of the 29th Interscience Conference on Antimicrobial Agents and Chemotherapy, Houston, Texas, 1989 Abstr. 1357.
   Google Scholar
• An account of Phase I tolerance studies with cilofungin.
   Google Scholar
• COPLEY-MERRIMAN CR, RANSBURG NJ, CRANE LR, KERK- ERING TM, PAPPAS PG, POTTAGE JC, HYSLOP DL: Cilo-fungin treatment of Candida esopbagitis : Preliminary Phase U results. Program and Abstracts of the 30th Inter-science Conference on Antimicrobial Agents and Chemother-apy, Atlanta, Georgia, 1990 Abstr. 581.
   Google Scholar
• Successful treatment of Candida esophagitis in preliminary Phase II studies.
   Google Scholar
• COPLEY-MERRIMAN CR, GALLIS H, GRAYBLLL JR, DOES- BELING BN, HYSLOP DL: Cilofungin treatment of dis-seminated cadidiasis: Preliminary Phase II results. Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, Geor-gia, 1990 Abstr. 582.
   Google Scholar
• A dose of 500 mg tid was effective for treatment of disseminated candidiasis in Phase II studies with cilofungin.
   Google Scholar
• DOEBBELING BN, FINE BD, PFALLER MA, SHEETZ CT, STOKES JB, WENZEL RP: Acute tubular necrosis (ATN)and anion-gap acidosis during therapy with cilofungin (LY-121019) in polyethylene glycol (PEG). Program and Abstracts of the 30th Interscience Conference on Antimicro-bial Agents and Chemotherapy, Atlanta, Georgia, 1990 Abstr. 583. Toxicity due to PEG-300 cosolvent used in cilofungin formulation.
   Google Scholar
• TURNER W, DEBONO M, LAGRANDEUR L, BURKHARDT F, RODRIQUEZ M, ZWEIFEL M, NISSEN J, CLINGERMAN K, GORDEE R, ZECKNER D, PARR T, TANG J: LY303366- A new semi-synthetic lipopeptide antifungal agent related to echinocandin B.- 2. Rigid, polyaromatic sidechains pro-viding oral activity. Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Che-motherapy, New Orleans, Louisiana, 1993 Abstr. 358. SAR describing the Lilly side chain echinocandin analogues.
   Google Scholar
• DEBONO M, TURNER WW, LAGRANDEUR L, BURKHARDT F, RODRIGUEZ M, ZWEIFEL M, NISSEN J, CLINGERMAN K, GORDEE R, ZECKNER D, BUTLER T, PARR T, TANG J: LY303366- A new semi-synthetic lipopeptide antifungal agent related to echinocandin B. Synthetic and struc-ture-activity studies. Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Che-motherapy, New Orleans, Louisiana, 1993 Abstr. 359.
   Google Scholar
• Poster describing the semi-synthesis and SAR of a number of polyaromatic side chain echinocandin analogues.
   Google Scholar
• TANG J, PARR TR, TURNER W, DEBONO M, LAGRANDUER L, BURKHARDT F, RODRIGUEZ M, ZWEIFEL M, NISSEN J, CLINGERMAN K: LY303366: A noncompetitive inhibitor of (1,3)-13-D-glucan synthases from Candida albicans and Aspergillus fumigatus . Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 367.
   Google Scholar
• Poster showing noncompetitive inhibition of LY303366. The Ki (1.1.M) was 0.7 and 0.11 for C. albicans and A. fumigatus.
   Google Scholar
• GORDEE R, FARMER J, FLOKOWITSCH J, FIAEBER P: In vitro antifungal activity of LY303366, a new antifungal agent derived from echinocandin B. Program and Ab-stracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana, 1993Ab-stract 360.
   Google Scholar
• Poster presenting the activity of LY303208, LY303366 and LY307863 against Candida, Aspergillus, Blastomyces, Histoplasma and Ciypto-coccus. Kill curves demonstrate the fungicidal nature of LY303366.
   Google Scholar
• ZECKNER D, BUTLER T, BOYLAN C, BOYLL B, LIN Y, RAAB P, SCHMIDTKE J, CURRENT W: LY303366, activity in a murine systemic candidiasis modeL Program and Ab-stracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 365.
   Google Scholar
• ED5o5 for LY303366 against systemic candidiasis were 0.3 mg/kg ip and 7.8 mg/kg po.
   Google Scholar
• ZECKNER D, BUTLER T, BOYLAN C, BOYLL B, LIN Y, RAAB P, SCHMIDTKE J, CURRENT W: LT303366, activity against systemic aspergillosis and histoplasmosis in murine models. Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 364.
   Google Scholar
• ED50 for LY303366 against systemic aspergillosis was 19.6 mg/kg ip, but was inactive orally up to 50 mg/kg.
   Google Scholar
• CURRENT W, BOYLAN CJ, RAAB PA: Anti-Pneumocystis activity of LY303366 and other echinocandin B analogs. Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 368. A 5 mg/kg oral dose of LY303366 gave 99.7% reduction of cysts from the lungs of infected rats in a model of PCP.
   Google Scholar
• ZORNES L, STRATFORD R, NOVILLA M, TURNER D, BOY- LAN C, BOYLL B, BUTLER T, LIN Y, ZECKNER D, TURNER W, CURRENT W: Single dose iv and oral administration pharmacokinetics of LY303366, a new lipopeptide an- tifungal agent related to echinocandin B, in female Lewis rats and beagle dogs. Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 370.
   Google Scholar
• Oral versus iv pharmacokinetic parameters for LY303366 and the phosphate ester prodrug, LY307853, show the absolute bioavailabil-ity to be 1.6% and 1.8% in rats and 4.3% and 4.5% in dogs, respectively. For '366, the terminal half-life in rats and dogs was 18.1 and 10.9 hours, respectively, while the half-life for '366 from the prodrug '853 was 22.4 and 10.7 hours in the two species, respectively.
   Google Scholar
• KUROKAWA N, OHFLTNE Y: Total synthesis of echino-candins. 2. Total synthesis of echinocandin D via effi-cient peptide coupling reactions. J. Am. Chem. Soc. (1986) 108:6043–6045.
   Google Scholar
• First total synthesis of an echinocandin natural product.
   Google Scholar
• KUROKAWA N, OHFUNE Y: Synthetic studies on antifun-gal cyclic peptides, echinocandins - Stereoselective total synthesis of echinocandin D via a novel peptide cou-pling. Tetrahedron (1993) 49:6195–6222.
   Web of Science ®Google Scholar
• Full account of the JACS communication. Attempts to prepare echinocandin B were unsuccessful.
   Google Scholar
• EVANS DA, WEBER AE: Synthesis of the cydic hexapep- tide echinocandin D. New approaches to the asymmet-ric synthesis of I3-hydroxy a-amino acids. J. Am, Chem. Soc. (1987) 109:7151-7157. Second synthesis of echinocandin D.
   Google Scholar
• BALKOVEC JM, BLACK RM: Reduction studies of antifun-gal echinocandin lipopeptides. One step conversion of echinocandin B to echinocandin C. Tetrahedron Lett. (1992) 33:4529–4532.
   Web of Science ®Google Scholar
• Describes selective reductions at the hemiaminal, and homotyrosine positions of the echinocandin and pneumocandin natural products.
   Google Scholar
• ZAMBIAS RA, HAMMOND ML, HECK JV, BARTIZAL K, TRAINOR C, ABRUZZO G, SCHMATZ DM, NOLLSTADT KM:Preparation and structure-activity relationships of sim-plified analogues of the antifungal agent cilofurtgin: A total synthesis approach. J. Med. Chem. (1992) 35:2843–2855.
   PubMed Web of Science ®Google Scholar
• Paper describes a series of increasingly complex analogues of cilofungin with glucan synthase and antifungal activities monitored along the way. Demonstrates the importance of the homotyrosine moiety vis-a-vis tyrosine and the 3-hydroxy-4-methylproline residue. First approach to utilize solid-phase peptide synthesis in the con-struction of the linear peptide and lipophilic side chain.
   Google Scholar
• ROY K, MUKHOPADHYAY T, REDDY GCS, DESIKAN KR,GANGULI BN: Mulundocandin, a new lipopeptide anti-biotic. L Taxonomy, fermentation, isolation and char-acterization. J. Antibiot. (1986) 40:275–280.
   Google Scholar
• MUKHOPADHYAY T, GANGULI BN: Mulundocandin, anew lipopeptide antibiotic. IL Structure elucidation. J. Anti biot. (1986) 40:281–289.
   Web of Science ®Google Scholar
• MUKHOPADHYAY T, ROY K, BHAT RG, SAWAN'T SN, BLUMBACH J, GANGULI BN, FEHLFIABER HW, KOGLER H: Deoxymuhmdocandin - A new echinocandin type anti-fungal antibiotic. J. Anti blot. (1992) 45:618–623.
   PubMed Web of Science ®Google Scholar
• PACHE W, DREYFUSS M, 'HUBER R, TSCHERTERH: Sporio-fungins, new antifungal antibiotics of the cyclopeptide group. In: Proceedings 13th International Congress of Che-motherapy, Vienna, Austria (1983):PS 4.8/3, Part 115, Abstr 10.
   Google Scholar
• SCHWARTZ RE, MASUREKAR P, WHITE R: Discovery, production process development, and isolation of pneumocandinBo. In: Cutaneous Antifungal Agents(1993).
   Google Scholar
• Rippon JW, Fromtling RA (Eds), Marcel Dekker, New York. Full account of the discovery of pneumocandin Bo
   Google Scholar
• SCHWARTZ RE, GIACOBBE RA, BLAND JA, MONAGHAN RL: L-671,329, a new antifungal agent L Fermentation and isolation. J. Antibiot. (1989) 42:163–167.
   PubMed Web of Science ®Google Scholar
• First pneumocandin to be isolated.
   Google Scholar
• WICHMANN CF, LIESCH JM, SCHWARTZ RE: L-671,329, a new antifungal agent IL Structure determination. J. Anti blot. (1989) 42:168-173_
   Google Scholar
• ADEFERATI AA, GIACOBBE RA, HENSENS OD, TKACZ JS: Biosynthesis of L-671,329, an echinocandin-type anti-biotic produced by Zalerion arboricola: Origins of some of the unusual amino acids and the di-methylmyristic acid side chain. J. Am, Chem. Soc. (1991) 113:3542–3545.
   Web of Science ®Google Scholar
• This biosynthetic investigation shows that the 3-hydroxy-4-methyl-proline is derived from leucine not proline. The unusual homotyros-ine is derived from tyrosine and acetate. Lastly, the methyl groups of the side chain come from methionine.
   Google Scholar
• NOBLE HM, LANGLEY D, SIDEBOTTOM PJ, LANE SJ, FISHER PJ: An echinocandin from an endophytic Cryp- tosporiopsis sp. and Pezicula sp. in Pinus sylvestris and Fagus sylvatica. Mycol. Res. (1991) 95:1439-1440. Pneumocandin Ao is also produced by Cryptosporiopsisand Pezicula species
   Google Scholar
• SCHWARTZ RE, SESIN DF, JOSHUA H, WILSON KB, KEMPFAJ, GOKLEN KR, KUEHNER D, GAILLIOT P, GLEASON C, WHITE R, INAMINE E, BILLS G, SALMON P, ZITANO L: Pneumocandins from Zalerion arboricola L Discovery and isolation_ J. Antibiot. (1992) 45:1853-1866, Isolation of pneumocandin Bo.
   Google Scholar
• MASUREKAR PS, FOUNTOULAKIS JM, HALLADA TC, SOSAMS KAPLAN L: Pneumocandins from Zalerion arbori-cola IL Modification of product spectrum by mutation and medium manipulation. J. Antibiot. (1992) 45:1867–1874.
   PubMed Web of Science ®Google Scholar
• ADEFARATI AA, HENSENS OD, JONES ETT, TKACZ JS: Pneumocandins from Zalerion arboricola V. Glutamic acid- and leucine-derived amino acids in pneurno-candin Ao (L-671,329) and distinct origins of the substi-tuted proline residues in pneumocandins Ao and Bo. J. Antibiot. (1992) 45:1953–1957.
   Google Scholar
• Discusses the distinct biogenesis of the proline residues of pneumo-candin Ao and pneumocandin Bo.
   Google Scholar
• FROMTLING RA, ABRUZZO GK: L-671,329, anew antlfun- gal agent. DI. In vitro activity, toxicity, and efficacy in comparison to aculeacin. j Antibiot. (1989) 42:174-178. A direct comparison in vitro and in vivo of pneumocandin Ao (L-671,329) and aculeacin. The compounds possess similar poten-cies.
   Google Scholar
• BARTIZAL K, ABRUZZO G, TRAINOR C, KRUPA D, NOLL- STADT K, SCHMATZ D, SCHWARTZ R, HAMMOND M, BALKOVEC J, VANMIDDLESWORTH F: In vitro antifungal activities and in vivo efficacies of 1,3-13-D-g1ucan synthe-sis inhibitors L-671,329, L-646,991, tetrahydroechino-candin B, and L-687,781, a papulacandin. Antimicrob. Agents Cbemother. (1992) 36:1648–1657.
   PubMed Web of Science ®Google Scholar
• Comparison of pneumocandin Ao, cilofungin and tetrahydroechino-candin B.
   Google Scholar
• SUNDELOF JG, HAJDU R, CLEARE WJ, ONISHI J, KROPP H: Pharmacokinetics of L-671,329 in rhesus monkeys and DBA/2 mice. Antimicrob. Agents Chemother. (1992) 36:607–610.
   PubMed Web of Science ®Google Scholar
• Pharmacokinetic comparison of pneumocandin Ao (L-671,329) and cilofungin in rhesus monkeys and mice.
   Google Scholar
• SCHMATZ DM, ABRUZZO G, POWLES MA, MCFADDEN DC, BALKOVEC JM, BLACK RM, NOLLSTADT K, BARTIZAL K: Pneurnocandins from Zalerion arboricola IV. Biologi-cal evaluation of natural and semisyrtthetic pneumo-candins for activity against Pneumocystis carinii and Candista species. J. Antibiot. (1992) 45:1886–1891.
   Google Scholar
• SAR and biological efficacies of the pneumocandins and deoxygen-ated derivatives. A diverging SAR for Candida and P. carinii is noted.
   Google Scholar
• BALKOVEC JM, BLACK RM, HAMMOND ML, HECK JV, ZAMBIAS RA, ABRUZZO G, BARTIZAL K, KROPP H, TRAI-NOR C, SCHWARTZ RE, MCFADDEN DC, NOLLSTADT ICH, PITTARELLI IA, POWLES MA, SCHMATZ DM: Synthesis, stability, and biological evaluation of water-soluble prodrugs of a new echinocandin lipopeptide. Discov-ery of a potential cl1n1c21 agent for the treatment of systemic cadidiasis and Pneumocystis carinii pneumo-nia (PCP). J. Med Chem. (1992) 35:194–198.
   Google Scholar
• Prodrugs of pneumocandin Bo (L-688,786) are described. The chemi-cally stable phosphate ester derivative, L-693,989, showed bio-equivalence to the parent compound in rodent models of candidiasis and PCP.
   Google Scholar
• BALKOVEC JM, BLACK RM, ABRUZZO GK, BARTIZAL K, DREIKORN S, NOLLSTADT K: Pneumocandin antifungal lipopeptides. The phenolic hydroxyl is required for 1,3-13-glucan synthesis inhibition. Bioorg. Med. Chem, Lett. (1993) 3:2039–2042.
   Google Scholar
• Removal of phenolic hydroxyl of homotyrosine residue of pneumo-candin Bo shows a 140-fold loss in glucan synthesis inhibition.
   Google Scholar
• BERNARD EM, EDWARDS FF, ARMSTRONG D, KURTZ MB: Activity of three pneumocandins in an animal model of pulmonary aspergillosis. Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 354.
   Google Scholar
• Study showed effectiveness of three pneumocandin derivatives, L-693,989, L-731,373 and L-733,560, in a rat model of pulmonary aspergillosis. L-733,560 was .effective when dosed at 0.625 mg/kg bid X7 .
   Google Scholar
• SCHMATZ DM, POWLES M, MCFADDEN DC, VADAS E, MEISNER D, HAJDU R: Treatment and prevention of P. carinii pneumonia in the rat using aerosolized water soluble lipopeptide L-693,989. Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, Illinois, 1991 Abstr. 208.
   Google Scholar
• Efficacy and prophylaxis with L-693,989 by aerosol delivery in a rat PCP model.
   Google Scholar
• BOUFFARD FA, ZAMBIAS RA, DROPINSKI JF, BALKOVEC JM, HAMMOND ML, NOLLSTADT KH, MARRINAN J: Syn-thesis and antifungal activity of water-soluble pneurno-candin Bo derivatives: L-705589, L-731373, and L-733560. Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 350. Synthesis of pneumocandin analogues L-705,589, L-731,373 and L-733,560 was described. The C. albicans glucan synthase inhibition ICsos were 11, 10 and 1 nM, respectively.
   Google Scholar
• KURTZ MB, MARRINAN J, ONISHI J, DREIKORN S, HEA'rH TB, DOUGLAS C: A morphological susceptibility assay to rank pneumocandin analogs against Aspergillus sp. Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 352.
   Google Scholar
• Morphological effects of pneumocandin derivatives on Aspergillus species was described.
   Google Scholar
• PACHOLOK C, LYNCH L, KROPP H, BARTIZAL K: In vitro evaluation of L-733,560, a new water soluble lipopep-tide hybrid of L-705,589 and L-731,373. Program and Abstracts of the 33rd Interscience Conference on Antimicro-bial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 351.
   Google Scholar
• MFC90 determinations, time-kill curves and serum antagonism of pneumocandin derivatives were presented.
   Google Scholar
• BARTIZAL K, ABRUZZO GK, FLATTERY AM, GILL CJ, SMITH JG, LYNCH L, PACHOLOK C, SCOTT T, KONG L, KROPP H:Anti-Candida in vivo efficacy of water soluble lipopep-tides L-705,589, L-731,373 and L-733,560. Program and Abstracts of the 33rd Interscience Conference on Antimicro-bial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 353.
   Google Scholar
• L-733,560 sterilized kidneys at _0.09 mg/kg ip, bid X4, in a mouse disseminated candidiasis model.
   Google Scholar
• ABRUZZO GK, FLA11LRY AM, GILL CJ, SMITH JG, KROPP H, BARTIZAL K: Evaluation of water soluble lipopeptidesL-733,560, L-705,589 and L-731,373 in a mouse model of disseminated aspergillosis. Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 355.
   Google Scholar
• L-733,560 and L-705,589 but not L-731,373, significantly prolonged survival in a mouse disseminated aspergillosis model at 0,02 mg/kg ip, bid X5.
   Google Scholar
• SCHMATZ DM, MCFADDEN DC, LIBERATOR P, ANDERSON OOJ, POWLES MA: Evaluation of new senuisynthetic pneu-mocandins against Pneumocystis carinii in the immu-nocompromised rat. Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Che-motherapy, New Orleans, Louisiana, 1993 Abstr. 356. L-733,560 was effective (ED9o) at 0.01 mg/kg in a rat PCP model.
   Google Scholar
• HAJDU R, THOMPSON R, WHITE K, STARK MURPHY B, KROPP H: Comparative pharmacokinetics of threewater-soluble analogues of the lipopetide antifungal compound L-688,786 in mice and rhesus monkeys. Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 357.
   Google Scholar
• L-733,560 showed superior rhesus pharmacokinetics compared to L-688,786, L-705,589 and L-731,373. IV dosing at 5 mg/kg gave plasma levels of 5 fig/mL for 24 hours.
   Google Scholar
• BOUFFARD FA, ZAMBIAS RA, DROPINSKI JF, BALKOVEC JM, HAMMOND ML, ABBRUZZO GK, BARTIZAL RE, MAR-RINAN JA, KURTZ MB, MCFADDEN DC, NOLLSTADT /CH, POWLES MA, SCHMATZ DM: Synthesis and antifungal activity of novel cationic pneumocandin Bo derivatives. J. Med. Chem. (1994) 37:(in press).
   Google Scholar
• Paper summarizing in vitro and in vivo activity of pneumocandin Bo, L-705,589, L-731,373 and L–733,560.
   Google Scholar
• IWAMOTO T, SAKAMOTO K, YAMASHITA M, EZAIU M, HASHIMOTO S, FURUTA T, OKUHARA M, KOHSAKA: FR901379, a novel antifungal antibiotic. Program and Abstracts of the 33rd Interscience Conference on Antimicro-bial Agents and Chemotherapy, New Orleans, Louisiana, 1993 Abstr. 371.
   Google Scholar
• FR901379 showed a survival ED% in a mouse disseminated candidi-asis model of 2.7 mg/kg. FR901381 and FR901382 were less effective.
   Google Scholar
• TAKESAKO K, IKAI K, HARLJNA F, ENDO M, SHIMANAKA K, SONO E, NAKAMURA T, KATO I, YAMAGUCHI H: Aureobasidins, new antifungal antibiotics taxonomy, fermentation, isolation, and properties. J. Antibiot. (1991) 44:919-924. Isolation and in vitro activity of aureobasidins A-R.
   Google Scholar
• IKAI K, TAKESAKO K, SHIOMI K, MORIGUCHI M, UMEDA Y, YAMAMOTO J, KATO I, NAGANAWA II: Structure of aureobaskiin-A. j Antibiot. (1991) 44:925–933.
   PubMed Web of Science ®Google Scholar
• IKAI K, SHIOMI K, TAKESAKO K, MIZUTANI S, YAMAMOTO J, OGAWA Y, UENO M, KATO I: Structures of aureobasid-ins B to R. J. Antibiot. (1991) 44:1187–1198.
   PubMedGoogle Scholar
• YOSHIKAWA Y, IKAI K, UMEDA Y, OGAWA A, TAKESAKO K, KATO I: Isolations, structures, and antifungal activi- ties of new aureobasidins. J. Antibiot. (1993)46:1347-1354. The structures and antifungal activities of aureobasidins Si, S2a, S2b, S3 and S4 are disclosed.
   Google Scholar
• TAKESAKO K, KURODA H, INOUE T, HARUNA F, YOSHIKAWA Y, KATO I, UCHIDA K, HIRATANI T, YAMA-GUCHI H: Biological properties of aureobasidin A, a cyclic depsipeptide antifungal antibiotic J. Antibiot. (1993) 46:1414–1420.
   Google Scholar
• Describes extensive in vitro and in vivo activity of aureohasidin A. Kill curves and acute toxicity is reported.
   Google Scholar
• BURTON PS, CONRADI RA, HILGERS AR: Mechanisms of peptide and protein absorption. Transcellular mecha-nism of peptide and protein absorption: passive as-pects. Advanced Drug Deliv. Rev. (1991) 7:365–386.
   Google Scholar
• Good discussion of factors affecting passive transport of peptides across cellular barriers. Presents a study showing effect of N-rnethy-lation of peptide bonds on transport across epithelium.
   Google Scholar
• GORDEE R, FARMER J, ZECKNER D: LY295337 a novel cyclic depsipeptide antifungal antibiotic. L In vitro antifungal activity. Program and Abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Che-motherapy, Anaheim, California, 1992, Abstr. 496.
   Google Scholar
• BUTLER T, ZECKNER D, BOYLAN C, RAAB P, THOMAS L, GORDEE R, LUBBEHUSEN P, COUNTER F, SCHMIDTKE J: LY295337 a novel depsipeptide antifungal antibiotic. 111. Resistance development studies. Program and Ab-stracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Anaheim, California, 1992, Abstr. 498.
   Google Scholar
• LY297337 did not induce resistance in C. albicans after twelve passages in the presence of sub-inhibitory concentrations of LY295337.
   Google Scholar
• ZECKNER D, BUTLER T, BOYLAN C, RAAB P, THOMAS L, FARMER J, GORDEE R, SCHMIDTKE J: LY295337 a novel depsipeptidle antifungal antibiotic. IL In vivo antifungal activity. Program and Abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Anaheim, California, 1992, Abstr. 497.
   Google Scholar
• NAJVAR L, ALBERT M, BOCANEGRA R, LUTHER M, CO- LUMBO A, GRAYBILL J: Efficacy of LY295337 (LY) in a rat model of pulmonary aspergillosis (PA) and cryptococ-cal meningitis (CM). Program and Abstracts of the 33nd Interscience Conference on Antimicrobial Agents and Che-motherapy, New Orleans, Louisiana, 1993, Abstr. 366.
   Google Scholar
• This study showed that LY295337 failed in the PA model and displayed poor activity in the CM model.
   Google Scholar
• FRANKMOLLE WP, LARSEN LK, CAPLAN FR, PA i IERSON GML, KNUBEL G, LEVINE IA, MOORE RE: Antifungal cyclic peptides from the terrestrial blue-green algaAnabaena-laxa .1. Isolation and biological properties. J. Antibiot. (1992) 45:1451–1457.
   Google Scholar
• FRANKMOLLE WP, KNUBEL G, MOORE RE, PA11ERSON GML: Antifamgal cyclic peptides from the terrestrial blue-green alga Anabaena-laxa .2. Structures of laxaphycins A, B, D and E. J. Antibiot. (1992) 45:1458–1466.
   Google Scholar
• MOON S-S, CHEM JL, MOORE RE, PATTERSON GML: Calo-phycin, a fungicidal cyclic decapepticle form the terres-trial blue-green alga Calothrixfusca. J. Os. Chem. (1992) 57:1097–1103.
   Google Scholar
• SANDRIN C, PEYPOUX F, MICHEL G: Coproduction of surfactin and iturin A, lipopeptides with surfactant and antifungal properties, byBacillussubtilis. Biotech. Appl. Biochem. (1990) 12:370–375.
   PubMed Web of Science ®Google Scholar
• ROWIN GL, MILLER JE, ALBERS-SCHONBERG G, ONISHI JC, DAVIS D, DULANEY EL: Verlamelin, a new antifungal agent. J. Antibiot. (1986) 39:1772–175.
   PubMed Web of Science ®Google Scholar