Title

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

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

Share

COinS