A new group of antibiotics, hydroxamic acid antimycotic antibiotics. II. The structure of neoenactins NL1 and NL2 and structure-activity relationship.
The structures of neoenactins (NEs) NL1 and NL2, novel antimycotic antibiotics produced by Streptoverticillium olivoreticuli in a precursor-oriented fashion, were elucidated by 1H and 13C NMR and mass spectroscopic studies. The structures of both antibiotics are closely related to that of NE-A, the major component of NE congeners, being classified in the group of hydroxamic acid antimycotic antibiotics in which L-serine and a diketo amine form a hydroxamic acid structure. To study the role of the carbonyl groups in the biological activities of the hydroxamic acid antimycotic antibiotics, NE-A was modified by reaction with various carbonyl reagents. In terms of antimycotic activity, the derivatives are classified into two distinct groups; the first ones are fairly comparable to but not exceeding and the second ones are less active than NE-A depending on their tendency to revert to NE-A by hydrolysis. In general, the biological activities of the derivatives are inversely proportional to their stabilities to hydrolysis.
Okada
H
H
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Yamamoto
K
K
Tsutano
S
S
Inouye
Y
Y
Nakamura
S
S
Furukawa
J
J
D000935:Antifungal Agents / Q000032:analysis* / Q000138:chemical synthesis / Q000494:pharmacology; D004355:Drug Stability; D006877:Hydroxamic Acids / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D006877:Hydroxamic Acids; C019022:neo-enactin