6736. Nystatin

Nomenclature

CAS number: 1400-61-9
Fungicidin; Biofanal (Pfleger); Diastatin; Candex (Miles); Candio-Hermal (Hermal); Mycostatin (BMS); Moronal (BMS); Nystan (BMS); O-V Statin (BMS).

Description and references

Polyene antifungal antibiotic complex containing 3 biologically active components, A1, A2, A3. Produced by Streptomyces noursei, S. aureus and other Streptomyces spp: Hazen, Brown, Science 112, 423 (1950); Proc. Soc. Exp. Biol. Med. 76, 93 (1951); Raubitscheck et al., Antibiot. Chemother. 2, 179 (1952); Cohen, Webb, Arch. Pediatr. 69, 414 (1952); Dutcher et al., Antibiot. Annu. 1953-1954, 191; eidem, Therapy of Fungus Diseases (Little, Brown, Boston, 1955) p 168. Review of early literature: Brown, Hazen, Trans. N.Y. Acad. Sci. 19 (1956-1957) pp 447-456. Purification: Vandeputte, US 2832719 (1958 to Olin Mathieson); Renella, US 3517100 (1970 to Am. Cyanamid). Chemistry and partial structure: Birch et al., Tetrahedron Lett. 1964, 1491; of nystatin A1 and A2: Shenin et al., Antibiotiki 13, 387 (1968). Structure of the aglycone: Manwaring et al., ibid. 1969, 5319. Complete structure of A1: Chong, Rickards, ibid. 1970, 5145; Borowski et al., ibid. 1971, 685. Revised structure: R. C. Pandey, K. L. Rinehart, J. Antibiot. 29, 1035 (1976). Stereochemical study of A1: J. M. Lancelin et al., Tetrahedron Lett. 29, 2827 (1988). Structure of A3: J. Zielinski et al., J. Antibiot. 41, 1289 (1988). Mechanism of action: R. W. Holz in Antibiotics vol. 5, pt. 2, F. E. Hahn, Ed. (Springer-Verlag, New York, 1979) pp 313-340. Toxicity study: H. Seneca, Antibiot. Annu. 1955-1956, 697. Comprehensive description: G. W. Michel, Anal. Profiles Drug Subs. 6, 341-421 (1977).

Chemical structure

Properties

Light yellow powder. Gradually decomposes above 160° without melting by 250°. [α]D25 -10° (glacial acetic acid); +21° (pyridine); +12° (DMF); -7° (0.1N HCl in methanol). uv max (ethanol): 290, 307, 322 nm. Exhibits strong reducing properties. Solubilities determined by Weiss et al., Antibiot. Chemother. 7, 374 (1957) in mg/ml at about 28°: water 4.0; methanol 11.2; ethanol 1.2; carbon tetrachloride 1.23; chloroform 0.48; benzene 0.28; ethylene glycol 8.75. Solns and aq suspensions begin to lose activity soon after prepn. Aq suspensions are stable for 10 minutes on heating to 100° at pH 7.0; also stable in moderately alkaline media, but labile at pH 9 and pH 2. Heat, light, and oxygen accelerate decompn. Activity not diminished by blood or serum. LD50 i.p. in mice: ≈200 mg/kg (Seneca).

Derivative

Nystatin A1.

Nomenclature

CAS number: 34786-70-4
C47H75NO17; mol wt 926.09.
C 60.96%, H 8.16%, N 1.51%, O 29.37%.

Therapeutic Category

Antifungal.

Therapeutic Category (Veterinary)

Antifungal; growth promotant.

Keywords

Antifungal (Antibiotics); Polyenes