Synthesis, Cytotoxicity, and Genotoxicity of 10-Aza-9-oxakalkitoxin, an N,N,O-Trisubstituted Hydroxylamine Analog, or Hydroxalog, of a Marine Natural Product

Authors

Sandeep Dhanju
Kapil Upadhyaya
Christopher A. Rice
Scott D. Pegan
Joe Media, Henry Ford HealthFollow
Frederick A. Valeriote, Henry Ford HealthFollow
David Crich

Recommended Citation

Dhanju S, Upadhyaya K, Rice CA, Pegan SD, Media J, Valeriote FA, and Crich D. Synthesis, Cytotoxicity, and Genotoxicity of 10-Aza-9-oxakalkitoxin, an N,N,O-Trisubstituted Hydroxylamine Analog, or Hydroxalog, of a Marine Natural Product. J Am Chem Soc 2020; 142(20):9147-9151.

Document Type

Article

Publication Date

5-20-2020

Publication Title

Journal of the American Chemical Society

Abstract

We describe the synthesis of 10-aza-9-oxakalkitoxin, an N,N,O-trisubstituted hydroxylamine-based analog, or hydroxalog, of the cytotoxic marine natural product kalkitoxin in which the -NMe-O- moiety replaces a -CHMe-CH(2)- unit in the backbone of the natural product. 10-Aza-9-oxakalkitoxin displays potent and selective cytotoxicity (IC(50) 2.4 ng mL(-1)) comparable to that of kalkitoxin itself (IC(50) 3.2 ng mL(-1)) against the human hepato-carcinoma cell line HepG2 over both the human leukemia cell line CEM and the normal hematopoietic CFU-GM. Like kalkitoxin, and contrary to the common expectation for hydroxylamines, 10-aza-9-oxakalkitoxin is not mutagenic.

PubMed ID

32364709

Volume

142

Issue

20

First Page

9147

Last Page

9151