Izumenolide

A low-mol.-weight DNase inhibitor from M. echinospora was isolated and its activity characterized.The inhibitor produced 50% inhibition of DNase I, DNase II, and DNases from Streptomyces 6016, 4290, and 4098 at concentrations of 6.1, 9, 9.7, 42, and 47 μg.Enzymic activity was inhibited by direct binding of the DNase inhibitor to DNase I; inhibition acted by a mixed type mechanism with K_i ≃3 × 10^-6M.DNA topoisomerase I from adenocarcinoma FM3A cells was completely inhibited (in DNA unwinding) by 2.6 μg/mL of the inhibitor; this was a lower concentration than required for the inhibitors dotriacolide or izumenolide.

Inhibition of a beta-lactamase of Streptomyces cacaoi by CP-45,899, izumenolide and cephamycins was investigated and compared with that of a beta-lactamase of Bacillus cereus. S. cacaoi enzyme could not hydrolyze CP-45,899. Instead, hydrolysis of benzylpenicillin by the enzyme was inhibited in the presence of CP-45,899. Although inhibition increased gradually with time, the inhibition line produced by CP-45,899 with time less curved than that produced by clavulanic acid and PS-5. Furthermore, preincubation of S. cacaoi beta-lactamase with CP-45,899 for up to 120 seconds did not obviously affect the degree of inhibition. When the concentration was lowered, it behaved as a competitive inhibitor, a Ki value being 6.2 X 10(-7) M. Izumenolide, on the other hand, did not inhibit the enzyme activity of S. cacaoi beta-lactamase at 1.28 X 10(-4) M, although it inhibited B. cereus enzyme slightly in a competitive manner. Oganomycins were inert to the both beta-lactamases.U