Picture of boy being examining by doctor at a tuberculosis sanatorium

Understanding our future through Open Access research about our past...

Strathprints makes available scholarly Open Access content by researchers in the Centre for the Social History of Health & Healthcare (CSHHH), based within the School of Humanities, and considered Scotland's leading centre for the history of health and medicine.

Research at CSHHH explores the modern world since 1800 in locations as diverse as the UK, Asia, Africa, North America, and Europe. Areas of specialism include contraception and sexuality; family health and medical services; occupational health and medicine; disability; the history of psychiatry; conflict and warfare; and, drugs, pharmaceuticals and intoxicants.

Explore the Open Access research of the Centre for the Social History of Health and Healthcare. Or explore all of Strathclyde's Open Access research...

Image: Heart of England NHS Foundation Trust. Wellcome Collection - CC-BY.

Minor groove binders substituted by lipophilic groups

Suckling, C.J. and Waigh, R.D. and Khalaf, A.L. and Parkinson, J. and Hunter, I.S. (2003) Minor groove binders substituted by lipophilic groups. In: 19th International Congress on Heterocyclic Chemistry. Elsevier, p. 98. ISBN 0-080443-04-4

Full text not available in this repository. Request a copy from the Strathclyde author

Abstract

The search for novel anti-infective and anticancer drugs ranges over many types of compound. Following earlier work into the synthesis of compounds that bind into the minor groove of DNA (based upon the well-known N-methylpyrrole amino acid monomer), we have extended our studies to develop compounds including a wide range of alternative heterocyclic rings and alkyl substituents (with Professor Roger Waigh, Pharmaceutical Sciences). [see references] For reasons of commercial significance, the detailed structures of these compounds cannot be disclosed until early 2003 but Scheme2 is illustrative. However we have been gratified to find that some of our compounds containing novel structural features have antibacterial activity against such key organisms as MRSA and Cryptosporidium as well as against a number of fungi including Aspergillus and Candida. Moreover, nmr studies have given us strong insight into the detailed binding of our compounds with DNA. The chief synthetic chemical problems to be solved relate to the efficient solid phase synthesis of compounds containing the new heterocyclic monomers and, in some cases, to the monomers themselves. These problems are being addressed in partnership with LINK Technologies, a local biotech company, through the Teaching Company Scheme. There are also major structural and biochemical problems to be tackled. Some of our active compounds have very potent and specific binding patterns to DNA; in order to make further progress in targeting specific genes, the structural basis for this must be understood. Having discovered significant antibacterial and antifungal activity we are also keen to confirm and extend preliminary results that indicate interference with the action of cytokines in some cell types.