Current bacteriocidal and fungicidal agents are unsatisfactory for use on sensitive soft tissue or mucous membrane. There is no known chemical agent which possesses broad-range bacteriocidal and fungicidal activity and is nonirritant towards ocular tissue. The discovery of such an agent would be useful for such divergent purposes as sterilization of soft contact lenses, as an antimicrobial agent for infant use, or for surgical scrubs and in dental hygiene.In this project, we will initiate a systematic search for such an agent by the utilization of a carefillly chosen lead compound: chlorhexidine. This compound is bacteriostatic with little fungistatic activity. Although it is the most satisfactory compound currently available for soft lens use, its disadvantages, primarily irritancy, are well known in the eye care industry.We will utilize two approaches simultaneously toward the discovery of a new agent. In the first, the lipophilic and electronic character of a specifically chosen set of compounds will be correlated, using Craig-Topliss analytic techniques, with biological activity. The second approach will depend upon our novel conception of the role of ion chelation in the activity of the lead compound. The site of chelation of this molecule will be altered to effect the thermodynamics of metal ion chelation. In all, fourteen compounds will be synthesized. The completion of this project will lead toward the development of agents of improved bacteriocidal and fungicidal activity.National Institute of Allergy and Infectious Diseases (NIAID)
