The Isolation and Structure Elucidation of Spirotetronate Lobophorins A, B, and H8 from Streptomyces sp. CB09030 and Their Biosynthetic Gene Cluster.

Lobophorins (LOBs) are a growing family of spirotetronate natural products with significant cytotoxicity, anti-inflammatory, and antibacterial activities. Herein, we report the transwell-based discovery of Streptomyces sp. CB09030 from a panel of 16 in-house Streptomyces strains, which has significant anti-mycobacterial activity and produces LOB A (1), LOB B (2), and LOB H8 (3). Genome sequencing and bioinformatic analyses revealed the potential biosynthetic gene cluster (BGC) for 1-3, which is highly homologous with the reported BGCs for LOBs. However, the glycosyltransferase LobG1 in S. sp. CB09030 has certain point mutations compared to the reported LobG1. Finally, LOB analogue 4 (O-ß-D-kijanosyl-(1→17)-kijanolide) was obtained through an acid-catalyzed hydrolysis of 2. Compounds 1-4 showed different antibacterial activities against Mycobacterium smegmatis and Bacillus subtilis, which revealed the varying roles of different sugars in their antibacterial activities.

In vivo antitumor activity of ZYD88, a Chinese herbal medicine, in animal models with S180 sarcoma and Ehrlich tumor.

Cancer is a leading cause of death in the world. The continuous development of effective and nontoxic therapeutic agents is a major task in the battle of cancer. We report the in vivo effects of a Chinese herbal medicine, ZYD88, on the inhibition of tumor growth in an S(180) xenograft animal model and the improvement of animal survival in the Ehrlich tumor model. Oral administration of ZYD88 in mice with the xenograft S(180) sarcoma significantly inhibited tumor growth in a dose-dependent manner. Moreover, ZYD88 given to the animals with Ehrlich ascitic tumors by gavage significantly prolonged the life span compared with that of animals treated with saline. In both animal models, the effects of ZYD88 were comparable to those of a standard chemotherapeutic agent, cyclophosphamide, although it had few side effects. These results clearly demonstrated the in vivo anticancer activity of ZYD88 in two different animal models and suggest that ZYD88 is a potential agent for the clinical management of cancer and warrants further preclinical and clinical investigations.

Inhibition of tumor growth and tumor metastasis by a Chinese herbal formula--ZYD88, in an animal model with metastatic Lewis lung carcinoma.

Tumor metastasis is the leading cause of cancer death. In the present study, we determined the effectiveness of ZYD88, a Chinese herbal formula, in the inhibition of tumor growth and distant tumor metastases to the lung and liver in an animal model with metastatic Lewis lung carcinoma (LLC). Treatment with ZYD88 in adult C57BL/6 mice with metastatic LLC produced dose-dependent deceases in primary tumor weight, the mitotic tumor cell number, microvessel density, distant tumor metastases and red blood cell immune complexes, while it significantly increased tumor necrosis, thymus cortical thickness, the thymus medullar reticular epithelial cell (REC) number, and the activity of red blood cell C3b receptors. Although cyclophosphamide inhibited tumor growth, it had no significant effects on distant tumor metastases, thymus cortical thickness, the thymus medullar REC number, red blood cell C3b receptor activity and red blood cell immune complexes. These results indicate that ZYD88 possesses significant anti-angiogenic, anti-tumor and anti-metastatic effects in this animal model, and warrants further investigation.