Two new series of synthetic renieramycins including 22-O-amino ester and hydroquinone 5-O-amino ester derivatives of renieramycin M were semi-synthesized and evaluated for their cytotoxicity against the metastatic non-small-cell lung cancer H292 and H460 cell lines. Interestingly, the series of 22-O-amino ester derivatives displayed a potent cytotoxic activity greater than the hydroquinone derivatives. The most cytotoxic derivative of the series was the 22-O-(N-Boc-l-glycine) ester of renieramycin M (5a: IC50 3.56 nM), which showed 7-fold higher potency than renieramycin M (IC50 24.56 nM) and 61-fold more than jorunnamycin A (IC50 217.43 nM) against H292 cells. In addition, 5a exhibited a significantly higher cytotoxic activity than doxorubicin (ca. 100 times). The new semi-synthetic renieramycin derivatives will be further studied and developed as potential cytotoxic agents for non-small-cell lung cancer treatment.
Keywords: 22-O-amino ester derivatives of renieramycin M; bistetrahydroisoquinolinequinone; chemical modification; cytotoxicity; hydroquinone 5-O-amino ester derivatives of renieramycin M; marine alkaloid; non-small-cell lung cancer; renieramycin M; semi-synthesis.