Benzastatin C

The structures of benzastatins A, B, C, and D, new free radical scavengers, were determined by spectroscopic studies. Benzastatins A and B incorporate the para-aminobenzamide unit which is rare in fungal metabolites. Benzastatins C and D are unique alkaloids related to virantmycin; they contain the tetrahydroquinoline unit in the molecules.

In the course of screening for free radical scavengers, rare metabolites, benzastatins A and B having aminobenzamide skeleton and benzastatins C and D having tetrahydroquinoline skeleton, were isolated from the culture broth of streptomyces nitrosporeus 30643. They showed inhibitory activity against lipid peroxidation in rat liver microsomes. In the cell assay, benzastatins C and D inhibited glutamate toxicity in N18-RE-105 cells with EC50 values of 2.0 and 5.4 microM, respectively.

Benzastatin C, a 3-chloro-tetrahydroquinolone alkaloid from Streptomyces nitrosporeus, showed antiviral activity in a dose-dependant manner with EC50 values of 1.92, 0.53, and 1.99 microg/ml against herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and vesicular stomatitis virus (VSV), respectively. In contrast, benzastatin D, the corresponding dechlorinated derivative, did not exhibit any antiviral activity. These results indicate that the antiviral activity of benzastatin C is mediated, in part, due to the chlorine moiety in its molecular structure.