Synthesis and antiproliferative activity of C- and N-terminal analogues of culicinin D

Freda F Li; Louise A Stubbing; Iman Kavianinia; Maria R Abbattista; Paul W R Harris; Jeff B Smaill; Adam V Patterson; Margaret A Brimble

doi:10.1016/j.bmcl.2020.127331

Synthesis and antiproliferative activity of C- and N-terminal analogues of culicinin D

Bioorg Med Chem Lett. 2020 Aug 15;30(16):127331. doi: 10.1016/j.bmcl.2020.127331. Epub 2020 Jun 9.

Authors

Freda F Li¹, Louise A Stubbing², Iman Kavianinia², Maria R Abbattista³, Paul W R Harris⁴, Jeff B Smaill³, Adam V Patterson³, Margaret A Brimble⁵

Affiliations

¹ School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland 1010, New Zealand.
² School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland 1010, New Zealand; The Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1010, New Zealand.
³ The Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1010, New Zealand; Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1010, New Zealand.
⁴ School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland 1010, New Zealand; The Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1010, New Zealand; School of Biological Sciences, The University of Auckland, 3A Symonds St, Auckland 1010, New Zealand.
⁵ School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland 1010, New Zealand; The Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1010, New Zealand; School of Biological Sciences, The University of Auckland, 3A Symonds St, Auckland 1010, New Zealand. Electronic address: m.brimble@auckland.ac.nz.

PMID: 32631536
DOI: 10.1016/j.bmcl.2020.127331

Abstract

Culicinin D (1), a 10 amino acid peptaibol containing several unusual residues, has been shown to exhibit potent anticancer activity. Previous work in our group towards developing a structure-activity relationship (SAR) for this peptaibol has concentrated on replacement of the synthetically challenging AHMOD (3) and AMD (4) residues, resulting in the discovery of analogues with equivalent or better potency and simplified synthesis. The SAR of this peptaibol is extended in this work by investigating the effect of the N-terminal lipid tail and C-terminal amino alcohol, revealing the key contribution of each of these moieties on antiproliferative activity in a panel of breast and lung cancer cell lines.

Keywords: Cancer; Culicinin D; Peptaibol.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Oligopeptides / chemical synthesis
Oligopeptides / chemistry
Oligopeptides / pharmacology*
Peptaibols / chemical synthesis
Peptaibols / chemistry
Peptaibols / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Oligopeptides
Peptaibols
culicinin D