Heteroarotinoids with two- and three-atom linkers as potential anticancer agents

Scope and method of study. The goal of this study was to design, synthesize, purify, and characterize various sulfur- and oxygen-containing heteroarotinoids possessing two- or three-atom linker groups between two aromatic rings. The linker groups, along with other structural characteristics, were incorporated to potentially endow the agents with specific anticancer qualities through RAR-γ selectivity, RXR subfamily selectivity, pan agonist qualities, or the ability to induce programmed cell death (apoptosis). More specifically, the agents were prepared with the anticipation of providing valuable insight into generating agents which were effective and possessed low toxicity for the treatment of ovarian, vulvar, and/or head and neck cancers.; Findings and conclusions. Methodology was developed and utilized for the production and characterization of sixteen new and novel heteroarotinoids. Although the heteroarotiniods generated have not yet been tested for their anticancer activity, it is expected that biological studies of these agents could certainly provide valuable information for the invention of potentially effective anticancer agents possessing high activity and relatively low toxicity. However, several of the heteroarotinoids were tested for antibacterial activity against Mycobacterium bovis. It was discovered that two heteroarotinoids possessed reasonable antibacterial properties against Mycobacterium bovis and that one novel heteroarotinoid demonstrated exceptional promise activity against the same bacteria. These observations were certainly encouraging, due to the similarity of Mycobacterium bovis to Mycobacterium tuberculosis, and infectious agent that causes tuberculosis and whose incidence is dramatically on the rise. Additional research is needed to establish the exact role of retinoids as antibacterial agents.; An interesting observation was made on the NMR spectral characteristics of certain heteroarotinoids containing a thiourea function as a three-atom linker. Further NMR spectral investigation of these heteroarotinoids was conducted to aid in establishing a possible explanation for the observed phenomenon.