Synthesis and biological activity of benzamide DNA minor groove binders

Gul Shahzada Khan; Lisa I Pilkington; David Barker

doi:10.1016/j.bmcl.2015.12.090

Synthesis and biological activity of benzamide DNA minor groove binders

Bioorg Med Chem Lett. 2016 Feb 1;26(3):804-808. doi: 10.1016/j.bmcl.2015.12.090. Epub 2015 Dec 28.

Authors

Gul Shahzada Khan¹, Lisa I Pilkington², David Barker³

Affiliations

¹ Department of Chemistry, Shaheed Benazir Bhutto University, Sheringal, Dir (Upper), Khyber Pakhtunkhwa, Pakistan; School of Chemical Sciences, University of Auckland, 23 Symonds St, Auckland, New Zealand.
² School of Chemical Sciences, University of Auckland, 23 Symonds St, Auckland, New Zealand.
³ School of Chemical Sciences, University of Auckland, 23 Symonds St, Auckland, New Zealand. Electronic address: d.barker@auckland.ac.nz.

PMID: 26739782
DOI: 10.1016/j.bmcl.2015.12.090

Abstract

A range of di- and triaryl benzamides were synthesised to investigate the effect of the presence and nature of a polar sidechain, bonding and substitution patterns and functionalisation of benzylic substituents. These compounds were tested for their antiproliferative activity as well as their DNA binding activity. The most active compounds in all assays were unsymmetrical triaryl benzamides with a bulky or alkylating benzylic substituent and a polar amino sidechain.

Keywords: Anti-proliferative; Benzamides; DNA binding agents; DNA melting analysis; Minor groove binders.

Publication types

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

MeSH terms

Alkylation
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Benzamides / chemical synthesis
Benzamides / chemistry*
Benzamides / pharmacology
Cell Line, Tumor
Cell Proliferation / drug effects
DNA / chemistry
DNA / metabolism*
Drug Screening Assays, Antitumor
Humans
Nucleic Acid Denaturation
Transition Temperature

Substances

Antineoplastic Agents
Benzamides
DNA