Maha Sultan Al-Mutairi
Department of Pharmaceutical Chemistry College of Pharmacy, King Saud University Saudia Arabia

Abstract:

DNA topoisomerase are the targets of a number of antibacterial and anticancer chemotherapeutic agents. The topological state of DNA is regulated by topoiso¬merases through the action of breaking and releasing DNA strands. These topo I and II are classified based on their mode of cleaving DNA. Recently, interest has been focused on compounds with the ability to inhibit both topo I and topo II enzymes. Examples of these mixed inhibitors include the acridine-4-carboxamide DACA, the imidazoacridanone, and various tetracyclic chromophores. The present work exploits a structural motif that combines cycloheptano[b]thiophene skeleton with other heterocyclic rings and carrying different substituents to be evaluated as topoisomerase I and II inhibitors. The desiged new compounds were synthesized starting with 2-Amino-cycloheptano[b]thiophene-3-carboxylate through different steps that will lead to formation diamino-key intermediate (1) which will undergo condensation cyclization reactions utilized different reagents to afford our target compounds. All of the newly synthesized compounds were subjected to structure elucidation using elemental analyses, IR, mass spectrometry and 1H NMR.

Topoisomerases Assay Measurement of the catalytic topoisomerases will be based on conversion of supercoiled DNA to relaxed DNA. The concentration of the test compounds that prevent 50% of the substrate from being converted to the product (IC50) will be calculated.

Keywords: DNA topoisomerase, antibacterial and anticancer chemotherapeutic agents