Novel resorcinol platforms with pharmaceutical applications

• Main Author: Cominetti, Marco
• Published: University of East Anglia 2015
• Subjects: 547
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.683991

The rationale behind this work is the discovery that a number of natural bromophenols from algae have antibiotic and antioxidant activities. Most natural compounds are based on phenol and catechol. Previous studies by the group investigated a novel class of halogenated compounds based on resorcinol dimers which showed a relatively high antimicrobial activity. In this work, the structures were modified further in order to develop a structure-activity relationship for these systems. A novel synthetic approach to brominated resorcinol dimers was developed to allow efficient synthesis of the products without chromatographic purification. The method was additionally applied to the synthesis of a novel class of tetrameric and hexameric derivatives. Halogenation and dehalogenation methods were put in place to provide additional variety to the derivatives accessible. A set of simplified structures, including benzophenones and xanthones, was also prepared for comparison. The polyvalent structure of the tetramers and hexamers was investigated and exploited for the synthesis of dendrimeric multicalix[4]arene structures, including an octacalix[4]arene presenting thirty two amines, as proof of concept for the development of novel dendrimers, and among these new potential transfection agents and DNA binding structures. The library of compounds thus obtained was screened for its effects on the viability of two cancer cell lines, MCF-7 and HL60. The results showed a varied profile, ranging from potent antiproliferative activity to compounds with very moderate effects. Additionally the potential antioxidant activity of the compounds was investigated with two in vitro assays and for their cytoprotective activity on MCF-7 cells.