Antiviral and Antimetabolic Activities of Neplanocins

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1985 Jul 1

PMID 2994559

Citations 39

Authors

E De Clercq

Affiliations

Soon will be listed here.

Abstract

Of a series of carbocyclic analogs of adenosine, in which the ribose moiety was replaced by a cyclopentenyl ring, neplanocin A, or (-)-9-[trans-2, trans-3-dihydroxy-4-(hydroxymethyl)cyclopent-4-enyl]adenine proved particularly effective in inhibiting the multiplication of DNA viruses (i.e., vaccinia), (-)RNA viruses (i.e., parainfluenza, measles, and vesicular stomatitis), and double-stranded RNA viruses (i.e., reo) in vitro in cell culture. Depending on the cells used, the MIC of neplanocin A for these viruses ranged from 0.01 to 4 micrograms/ml, and depending on the parameter used to assess toxicity for the host cell, the specificity index of neplanocin A ranged from 50 to 4,000. As postulated before for other adenosine analogs, neplanocin A may owe its antiviral action to inhibition of S-adenosylhomocysteine hydrolase, hence perturbation of transmethylation reactions. In vivo, neplanocin A afforded only marginal protection against a lethal infection of mice with vesicular stomatitis virus.

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References

Borchardt R, Keller B . Neplanocin A. A potent inhibitor of S-adenosylhomocysteine hydrolase and of vaccinia virus multiplication in mouse L929 cells. J Biol Chem. 1984; 259(7):4353-8. View

Yaginuma S, Muto N, Tsujino M, Sudate Y, Hayashi M, Otani M . Studies on neplanocin A, new antitumor antibiotic. I. Producing organism, isolation and characterization. J Antibiot (Tokyo). 1981; 34(4):359-66. DOI: 10.7164/antibiotics.34.359. View

Giziewicz J, De Clercq E, Luczak M, SHUGAR D . Antiviral and antimetabolic activities of formycin and its N1-, N2-, 2'-O- and 3'-O-methylated derivatives. Biochem Pharmacol. 1975; 24(19):1813-7. DOI: 10.1016/0006-2952(75)90462-1. View

Shipman Jr C, Smith S, Carlson R, DRACH J . Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in synchronized suspension cultures. Antimicrob Agents Chemother. 1976; 9(1):120-7. PMC: 429485. DOI: 10.1128/AAC.9.1.120. View

De Clercq E, Descamps J, DE SOMER P, Holyacute A . (S)-9-(2,3-Dihydroxypropyl)adenine: An Aliphatic Nucleoside Analog with Broad-Spectrum Antiviral Activity. Science. 1978; 200(4341):563-5. DOI: 10.1126/science.200.4341.563. View

De Clercq E, Descamps J, Verhelst G, Walker R, Jones A, Torrence P . Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus. J Infect Dis. 1980; 141(5):563-74. DOI: 10.1093/infdis/141.5.563. View

Montgomery J, Clayton S, Thomas H, SHANNON W, Arnett G, Bodner A . Carbocyclic analogue of 3-deazaadenosine: a novel antiviral agent using S-adenosylhomocysteine hydrolase as a pharmacological target. J Med Chem. 1982; 25(6):626-9. DOI: 10.1021/jm00348a004. View

Hayashi M, Yaginuma S, Yoshioka H, Nakatsu K . Studies on neplanocin A, new antitumor antibiotic. II. Structure determination. J Antibiot (Tokyo). 1981; 34(6):675-80. DOI: 10.7164/antibiotics.34.675. View

De Clercq E, Bergstrom D, Holy A, Montgomery J . Broad-spectrum antiviral activity of adenosine analogues. Antiviral Res. 1984; 4(3):119-33. DOI: 10.1016/0166-3542(84)90012-3. View

10.

Hayashi M, Yaginuma S, Muto N, Tsujino M . Structures of neplanocins, new antitumor antibiotics. Nucleic Acids Symp Ser. 1980; (8):s65-7. View

11.

Bodner A, CANTONI G, Chiang P . Anti-viral activity of 3-deazaadenosine and 5'-deoxy-5'-isobutylthio-3-deazaadenosine (3-deaza-SIBA). Biochem Biophys Res Commun. 1981; 98(2):476-81. DOI: 10.1016/0006-291x(81)90864-0. View

12.

Chiang P, Guranowski A, Segall J . Irreversible inhibition of S-adenosylhomocysteine hydrolase by nucleoside analogs. Arch Biochem Biophys. 1981; 207(1):175-84. DOI: 10.1016/0003-9861(81)90023-0. View

13.

De Cercq E, Luczak M . Fluoroimidazoles as antiviral agents and inhibitors of polynucleotide biosynthesis. Life Sci. 1975; 17(2):187-94. DOI: 10.1016/0024-3205(75)90502-0. View

14.

Guranowski A, Montgomery J, CANTONI G, Chiang P . Adenosine analogues as substrates and inhibitors of S-adenosylhomocysteine hydrolase. Biochemistry. 1981; 20(1):110-5. DOI: 10.1021/bi00504a019. View

15.

Gephart J, Lerner A . Comparison of the effects of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine 5'-monophosphate against herpes simplex virus, varicella-zoster virus, and cytomegalovirus with their effects on cellular deoxyribonucleic acid synthesis. Antimicrob Agents Chemother. 1981; 19(1):170-8. PMC: 181377. DOI: 10.1128/AAC.19.1.170. View

16.

Bryson Y, Connor J . In vitro susceptibility of varicella zoster virus to adenine arabinoside and hypoxanthine arabinoside. Antimicrob Agents Chemother. 1976; 9(3):540-3. PMC: 429566. DOI: 10.1128/AAC.9.3.540. View

17.

De Clercq E, Holy A . Antiviral activity of aliphatic nucleoside analogues: structure-function relationship. J Med Chem. 1979; 22(5):510-3. DOI: 10.1021/jm00191a010. View

18.

BADER J, Brown N, Chiang P, CANTONI G . 3-Deazaadenosine, an inhibitor of adenosylhomocysteine hydrolase, inhibits reproduction of Rous sarcoma virus and transformation of chick embryo cells. Virology. 1978; 89(2):494-505. DOI: 10.1016/0042-6822(78)90191-5. View

19.

De Clercq E, Montgomery J . Broad-spectrum antiviral activity of the carbocyclic analog of 3-deazaadenosine. Antiviral Res. 1983; 3(1):17-24. DOI: 10.1016/0166-3542(83)90011-6. View