Associate editor: K.E. Suckling Minor groove binders as anti-infective agents Michael P. Barrett a , Curtis G. Gemmell b , Colin J. Suckling c, ⁎ a Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building University of Glasgow, 120 University Place, Glasgow, G12 8TA, Scotland, United Kingdom b University of Glasgow Medical School, Strathclyde Institute for Pharmacy and Biomedical Sciences, 161 Cathedral Street, Glasgow, G4 0RE, Scotland, United Kingdom c WestCHEM Research School, Department of Pure & Applied Chemistry, Thomas Graham Building, 295 Cathedral Street, Glasgow, G1 1XL, Scotland, United Kingdom abstract article info Keywords: Anti-infectives Anti-parasitics Anti-bacterials DNA Minor groove binders Diamidines Distamycin derivatives Minor groove binders are small molecules that form strong complexes with the minor groove of DNA. There are several structural types of which distamycin and netropsin analogues, oligoamides built from heterocyclic and aromatic amino acids, and bis-amidines separated by aromatic and heterocyclic rings are of particular pharmaceutical interest. These molecules have helical topology that approximately matches the curvature of DNA in the minor groove. Depending upon the precise structure of the minor groove binder, selectivity can be obtained with respect to the DNA base sequence to which the compound binds. Minor groove binders have found substantial applications in anti-cancer therapy but their significance in anti-infective therapy has also been significant and is growing. For example, compounds of the bis-amidine class have been notable contributors to antiparasitic therapy for many years with examples such as berenil and pentamidine being well-known. A recent growth area has been inreased sophistication in the oligoamide class. High sequence selectivity is now possible and compounds with distinct antibacterial, antifungal, antiviral, and antiparasitic activity have all been identified. Importantly, the structures of the most active compounds attacking the various infective organisms differ significantly but not necessarily predictively. This poses interesting ques- tions of mechanism of action with many different targets involved in DNA processing being candidates. Ac- cess of compounds to specific cell types also plays a role and in some cases, can be decisive. Prospects for a range of selective therapeutic agents from this class of compounds are higher now than for some consider- able time. © 2013 Elsevier Inc. All rights reserved. Contents 1. Introduction, Minor groove binders—structural types . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2. Minor groove binders in therapeutic use or in clinical trials . . . . . . . . . . . . . . . . . . . . . . . . . 0 3. Minor groove binders (MGBs) in antiparasitic therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4. Minor groove binders (MGBs) in antibacterial therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 5. Other anti-infective therapeutic areas using minor groove binders (MGBs) . . . . . . . . . . . . . . . . . . . 0 6. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 1. Introduction, Minor groove binders—structural types The term ‘minor groove binder’ (MGB) refers to many different clas- ses of compound that have the property of binding, often strongly, to the minor groove of DNA. Such compounds may be natural products (Fig. 1) or synthetic compounds (Fig. 2). There are several types of natural product with minor groove binding properties and these have been recognised for many years. Among the simpler structures are the polyamides, netropsin and distamycin (Finlay et al., 1951; Arcamone et al., 1967, 1989). These compounds bind to the minor groove principal- ly at AT rich regions (Abu-Daya et al., 1995). In the case of netropsin, a sin- gle molecule binds in the minor groove but in the case of distamycin and its analogues, it is more usual to find two molecules binding in a widened Pharmacology & Therapeutics xxx (2013) xxx–xxx ⁎ Corresponding author. E-mail addresses: michael.barrett@glasgow.ac.uk (M.P. Barrett), c.j.suckling@strath.ac.uk (C.J. Suckling). JPT-06544; No of Pages 12 0163-7258/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pharmthera.2013.03.002 Contents lists available at SciVerse ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Please cite this article as: Barrett, M.P., et al., Minor groove binders as anti-infective agents, Pharmacol. Ther. (2013), http://dx.doi.org/10.1016/ j.pharmthera.2013.03.002