Chemistry of Renieramycins. Part 19: Semi-Syntheses of 22-O-Amino Ester and Hydroquinone 5-O-Amino Ester Derivatives of Renieramycin M and Their Cytotoxicity against Non-Small-Cell Lung Cancer Cell Lines.

Abstract

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.

• Authors: Supakarn Chamni, Natchanun Sirimangkalakitti, Pithi Chanvorachote, Khanit Suwanborirux, Naoki Saito
• Journal: Marine drugs (Mar Drugs) Vol. 18 Issue 8 (Aug 10 2020) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 32785022 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Tetrahydroisoquinolines
• renieramycin M

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Humans
• Inhibitory Concentration 50
• Lung Neoplasms (drug therapy, pathology)
• Molecular Structure
• Structure-Activity Relationship
• Tetrahydroisoquinolines (chemical synthesis, pharmacology)