Four neoantimycins H-K (1-4) with C1-keto, including the new ones (1-2), were isolated from the culture of Streptomyces conglobatus RJ8. After enzymatically converting into their respective reduced type derivatives (5-8) in vitro, the absolute structures of 1-8 were established/reconfirmed by analyzing hydrolyzed components. The obtained NATs (4, 7, and 8) exhibited excellent cytotoxicity against drug-resistant colon and gastric cancer cells but low toxicity in the noncancerous cell. Further SAR investigation suggested that C1-hydroxyl, C9-isobutyl, and N-formyl contribute to the antiproliferation remarkably.
Keywords: absolute structure; apoptosis; drug-resistant cancer cell lines; enzymatically conversion; neoantimycins; streptomyces conglobatus; structural characterization; structure-activity relationship.