Synthesis of Novel Triynes and Investigation of Their Antibiotic Activity

Antibiotic resistance is a threat to future human health, especially as the incidence of infections rises and biofilm formation remains a possibility in the hospital setting. Antibiotics with new methods of action are needed to combat this threat, especially regarding biofilms, which are already resistant to many current antibiotics. Polyynes (polyacetylenes) are a class of natural products that contain more than one conjugated carbon-carbon triple bond. They display a wide variety of biological effects such as antifungal, antibacterial, and anti-cancer, and they are a promising class of molecules to investigate for novel antibiotics. Previously, several diynes have been identified by the Hinkle and Young labs that have potent biological activity against E. coli, P. fluorescens, and biofilm cultures. This thesis focuses on the synthesis and biological testing of triyne libraries based on the most biologically active diynes. A series based around 2-propyn-1-ol was synthesized and showed less potent antibacterial activity than the related diynes, showing that a third conjugated triple bond does not increase biological activity. Another series based around 1-heptyn-4-ol was synthesized and showed less potent antibacterial activity than the related diynes against planktonic bacteria. Some compounds in this triyne series, however, had potent biofilm-enhancing properties. Overall, diynols are far more potent antibacterials and anti-biofilm molecules than their triyne counterparts and hold promise as future antibiotics.