Claims
- 1. The antiviral antibiotic designated BU-3889V A.sub.1 which, when purified, is in the form of a pale yellow solid having a melting point above 250.degree. C.; a specific optical rotation [.alpha.].sup.25 of +180 degrees (C 0.56, H.sub.2 O); a molecular weight of 1504; an R.sub.f value in thin layer chromatographic analysis using silica gel of 0.05 with n--BuOH--n--PrOH--conc. NH.sub.4 OH--H.sub.2 O, 3:3:1:1 and of 0.22 using reversed phase silica gel with MeOH-0.022M phosphate buffer, pH 7.0, 50:50; is soluble in water, dimethylformamide and dimethyl sulfoxide and slightly soluble in methanol and acetone; gives a positive response to anthrone reagent, iodine, ferric chloride, Tollen's reagent and 2,4-dinitrophenylhydrazine, and a negative response in the ninhydrin, Sakaguchi and Ehrilich's tests; is labile to light; gives an infrared spectrum substantially as shown in FIG. 6; gives a high performance liquid chromatographic spectrum substantially as shown in FIG. 2; gives the .sup.13 C-NMR nuclear magnetic resonance spectrum substantially as shown in Table 3; gives .sup.1 H-NMR spectrum substantially as shown in FIG. 12 and is effective in inhibiting the growth of viruses.
- 2. The antiviral antibiotic designated BU-3889V A.sub.2 which, when purified, is in the form of a pale yellow solid having a melting point above 250.degree. C.; a specific optical rotation [.alpha.].sup.25 of +108 degrees (C 0.55, H.sub.2 O); a molecular weight of 1506; an R.sub.5 value in thin layer chromatographic analysis using silica gel of 0.05 with n--BuOH--n--PrOH--conc. NH.sub.4 OH--H.sub.2 O, 3:3:1:1 and of 0.43 using reversed phase silica gel with MeOH-0.022M phosphate buffer, pH 7.0, 50:50; is soluble in water, dimethylformamide and dimethyl sulfoxide and slightly soluble in methanol and acetone; gives a positive response to anthrone reagent, iodine, ferric chloride, Tollen's reagent and 2,4-dinitrophenylhydrazine, and a negative response in the ninhydrin, Sakaguch and Ehrlich's tests; which is labile to light; gives an infrared spectrum substantially as shown in FIG. 7; gives a high performance liquid chromatographic spectrum substantially as shown in FIG. 3; and is effective in inhibiting the growth of viruses.
- 3. The antiviral antibiotic designated BU-3889V A.sub.3 which, when purified, is in the form of a pale yellow solid having a melting point above 250.degree. C.; a specific optical rotation [.alpha.].sup.25 of +36 degrees (C 0.55, H.sub.2 O); a molecular weight of 1508; an R.sub.5 value in thin layer chromatographic analysis using silica gel of 0.05 with n--BuOH--n--PrOH--conc. NH.sub.4 OH--H.sub.2 O, 3:3:1:1 and of 0.55 using reversed phase silica gel with MeOH-0.022M phosphate buffer, pH 7.0, 50:50; is soluble in water, dimethylformamide and dimethyl sulfoxide and slightly soluble in methanol and acetone; gives a positive response to anthrone reagent, iodine, ferric chloride, Tollen's reagent and 2,4-dinitrophenylhydrazine, and a negative response in the ninhydrin, Sakaguchi and Ehrlich's tests; which is labile to light; gives an infrared spectrum substantially as shown in FIG. 8; gives a high performance liquid chromatographic spectrum substantially as shown in FIG. 4; gives the .sup.1 H nuclear magnetic resonance spectrum substantially as shown in FIG. 13; and is effective in inhibiting the growth of viruses.
- 4. The antiviral antibiotic designated BU-3889V D.sub.1 which, when purified, is in the form of a pale yellow solid having a melting point above 250.degree. C.; a specific optical rotation [.alpha.].sup.25 of +34 degrees (C 0.5, pyridine); a molecular weight of 1180; an R.sub.f value in thin layer chromatographic analysis using silica gel of 0.34 with n--BuOH--n--PrOH--conc. NH.sub.4 OH--H.sub.2 O, 3:3:1:1 and of 0.10 using silica gel with MeOH-0.022M phosphate buffer, pH 7.0, 50:50; is soluble in dimethylformamide and dimethyl sulfoxide and slightly soluble in methanol and acetone; gives a positive response to iodine, ferric chloride, Tollen's reagent and 2,4-dinitrophenylhydrazine, and a negative response in the anthrone, ninhydrin, Sakaguchi and Ehrlich's tests; which is labile to light; gives an infrared spectrum substantially as shown in FIG. 9; gives a high pressure liquid chromatographic spectrum substantially as shown in FIG. 5; gives the .sup.13 C-nuclear magnetic resonance substantially as shown in Table 3; gives .sup.1 H-NMR substantially as shown in FIG. 14 and is effective in inhibiting the growth of viruses.
- 5. The antiviral antibiotic designated BU-3889V D.sub.2 which, when purified, is in the form of a pale yellow amorphous powder having a melting point above 250.degree. C.; a specific optical rotation of [.alpha.].sup.26 .sub.D of -13.degree. (C 0.4, pyridine); a molecular weight of 1182 as determined by FAB-MS; an R.sub.5 value in thin layer chromatographic analysis using silica gel of 0.30 with n--BuOH--n--PrOH--conc. NH.sub.4 OH--H.sub.2 O, 3:3:1:1 and of 0.14 using reversed phase silica gel with MeOH-0.022 M phosphate buffer, pH 7.0, 50:50 v/v; is soluble in dimethylformamide and dimethyl sulfoxide and slightly soluble in methanol and acetone; gives a positive response to iodine, ferric chloride, Tollen's reagent and 2,4-dinitrophenylhydrazine and a negative response in the anthrone, ninhydrin, Sakaguchi and Ehrlich's tests; is labile to light; gives an infrared spectrum substantially as shown in FIG. 16; gives a high performance liquid chromatographic spectrum substantially as shown in FIG. 20; gives a .sup.1 H-NMR spectrum substantially as shown in FIG. 18; exhibits the following UV absorption maxima:
- ______________________________________UV .lambda..sub.max.sup.nm (.epsilon.):______________________________________in H.sub.2 O 237 (62,200) 301 (50,400)in 0.01N HCl 237 (52,000) 302 (42,900)in 0.01N NaOH 237 (65,400) 301 (49,900);______________________________________
- and is effective in inhibiting the growth of herpes simplex virus type 1 and influenza virus A.
- 6. The antiviral antibiotic designated BU-3889V D.sub.3 which, when purified, is in the form of a pale yellow amorphous powder having a melting point above 250.degree. C.; a specific optical rotation [.alpha.].sup.26 .sub.D of -17.degree. (C 0.4, pyridine); a molecular weight of 1184 as determined by FAB-MS; an R.sub.f value in thin layer chromatographic analysis using silica gel of 0.28 with n--BuOH--n--PrOH--conc NH.sub.4 OH--H.sub.2 O, 3:31:1, and of 0.18 using reversed phase silica gel with MeOH-0.022M phosphate buffer, pH 7.0, 50:50 v/v; is soluble in dimethylformamide and dimethyl sulfoxide and slightly soluble in methanol and acetone; gives a positive response to iodine, ferric chloride, Tollen's reagent and 2,4-dinitrophenylhydrazine, and a negative response in the ninhydrin, Sakaguchi and Ehrlich's tests; is anthrone labile to light; gives an infrared spectrum substantially as shown in FIG. 17; gives a high performance liquid chromatographic spectrum substantially as shown in FIG. 20; gives a .sup.1 H-NMR spectrum substantially as shown in FIG. 19; exhibits the following UV absorption maxima:
- ______________________________________UV .lambda..sub.max.sup.nm (.epsilon.):______________________________________in H.sub.2 O 237 (54,200) 300 (47,200)in 0.01N HCl 237 (41,000) 301 (37,900)in 0.01N NaOH 237 (57,100) 300 (45,200);______________________________________
- gives a .sup.13 C-NMR spectrum which exhibits the signals shown in Table 7; and is effective in inhibiting the growth of herpes simplex virus type 1 and influenza virus A.
- 7. The antiviral antibiotic complex designated BU-3889V produced by aerobic fermentation of a BU-3889V producing strain of Amycolatopsis orientalis ATCC-53884 under submerged aerobic conditions in a growth medium containing a source of assimilable nitrogen and carbon and containing the antiviral antibiotics designated BU-3889V A.sub.1, BU-3889V A.sub.2, BU-3889V A.sub.3 and BU-3889V D.sub.1, BU-3889V D.sub.2 and BU-3889V D.sub.3.
- 8. A pharmaceutical composition comprising an amount effective to inhibit the growth of viruses of the antiviral antibiotic BU-3889V A.sub.1 according to claim and a pharmaceutically acceptable carrier.
- 9. A pharmaceutical composition comprising an amount effective to inhibit the growth of viruses of the antiviral antibiotic BU-3889V A.sub.2 according to claim 2 and a pharmaceutically acceptable carrier.
- 10. A pharmaceutical composition comprising an amount effective to inhibit the growth of viruses of the antiviral antibiotic BU-3889V A.sub.3 according to claim 3 and a pharmaceutically acceptable carrier.
- 11. A pharmaceutical composition comprising an amount effective to inhibit the growth of viruses of the antiviral antibiotic BU-3889V D.sub.1 according to claim 4 and a pharmaceutically acceptable carrier.
- 12. A pharmaceutical composition comprising an amount effective to inhibit the growth of viruses of the antiviral antibiotic BU-3889V D.sub.2 according to claim 5 and a pharmaceutically acceptable carrier.
- 13. A pharmaceutical composition comprising an amount effective to inhibit the growth of viruses of the antiviral antibiotic BU-3889V D.sub.3 according to claim 6 and a pharmaceutically acceptable carrier.
- 14. A pharmaceutical composition comprising an amount effective to inhibit the growth of viruses of the antiviral antibiotic complex BU-3889V according to claim 7 and a pharmaceutically acceptable carrier.
CROSS-REFERENCE TO RELATED APPLICATIONS
application is a continuation-in-part of our co-pending application Ser. No. 536,746 filed June 14, 1990, now abandoned, which is a continuation-in-part of application Ser. No. 377,036 filed July 10, 1989, now abandoned.
US Referenced Citations (3)
| Number |
Name |
Date |
Kind |
| 4675187 |
Konishi et al. |
Jun 1987 |
|
| 4916065 |
Ohkuma et al. |
Apr 1990 |
|
| 4960755 |
Nishio et al. |
Oct 1990 |
|
Non-Patent Literature Citations (2)
| Entry |
| Sandstrom et al., Anti-Viral Therapy in AIDS, AIDS Press Limited, pp. 373-390, 1987. |
| Mitsuya et al., Retroviruses in Human Lymphoma/Leukemia, "Protection of T Cells Against Infectivity and Cytopathic Effect of HTLV-III in Vitro", pp. 277-288, 1985. |
Continuation in Parts (2)
|
Number |
Date |
Country |
| Parent |
536746 |
Jun 1990 |
|
| Parent |
377036 |
Jul 1989 |
|
Patent Grant
5098708
