An evaluation of Minor Groove Binders as anti-lung cancer therapeutics

Fraser J Scott; Mireia Puig-Sellart; Abedawn I Khalaf; Catherine J Henderson; Gareth Westrop; David G Watson; Katharine Carter; M Helen Grant; Colin J Suckling

doi:10.1016/j.bmcl.2016.06.040

An evaluation of Minor Groove Binders as anti-lung cancer therapeutics

Bioorg Med Chem Lett. 2016 Aug 1;26(15):3478-86. doi: 10.1016/j.bmcl.2016.06.040. Epub 2016 Jun 16.

Authors

Fraser J Scott¹, Mireia Puig-Sellart², Abedawn I Khalaf¹, Catherine J Henderson³, Gareth Westrop², David G Watson², Katharine Carter², M Helen Grant³, Colin J Suckling¹

Affiliations

¹ WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.
² Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom.
³ Department of Biomedical Engineering, University of Strathclyde, Wolfson Centre, Glasgow G1 0NW, United Kingdom.

PMID: 27349332
DOI: 10.1016/j.bmcl.2016.06.040

Abstract

A series of 47 structurally diverse MGBs, derived from the natural product distamycin, was evaluated for anti-lung cancer activity by screening against the melanoma cancer cell line B16-F10. Five compounds have been found to possess significant activity, more so than a standard therapy, Gemcitabine. Moreover, one compound has been found to have an activity around 70-fold that of Gemcitabine and has a favourable selectivity index of greater than 125. Furthermore, initial studies have revealed this compound to be metabolically stable and thus it represents a lead for further optimisation towards a novel treatment for lung cancer.

Keywords: Anti-cancer; Lung cancer; Minor Groove Binders.

MeSH terms

Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / isolation & purification
Antineoplastic Agents, Phytogenic / pharmacology*
Biological Products / chemistry
Biological Products / isolation & purification
Biological Products / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Deoxycytidine / analogs & derivatives*
Deoxycytidine / chemistry
Deoxycytidine / isolation & purification
Deoxycytidine / pharmacology
Distamycins / chemistry
Distamycins / isolation & purification
Distamycins / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Gemcitabine
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / pathology
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents, Phytogenic
Biological Products
Distamycins
Deoxycytidine
stallimycin
Gemcitabine