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Current Trends in Medicinal Chemistry
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Volume 5
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Three sulfonamide drugs that inhibit methicillin resistant (MRSA) and susceptible (MSSA) Staphylococcus aureus
Ronald Bartzatt, Suat L. G. Cirillo, Jeffrey D. Cirillo
Pages: 15 - 20
Number of pages: 6
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Current Trends in Medicinal Chemistry
Volume 5
Copyright © 2008 Research Trends. All rights reserved
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Staphylococcus aureus (S. aureus) is a major cause of hospital acquired infections. S. aureus causes skin lesions, other serious infections, food poisoning, and deeply penetrative infections such as endo-carditis. Three drug structures were synthesized by reaction of benzenesulfonyl chloride with various substituted aniline compounds. The result is a sulfonamide type aromatic drug structure which was placed in tissue culture with methicillin resistant (MRSA) and methicillin susceptible (MSSA) S. aureus. Growth inhibition of S. aureus was monitored by optical density and colony forming units. Experimental drugs A, B, and C showed comparable growth inhibition of MSSA as that observed with streptomycin. Drugs A, B, and C induced more than 50% inhibition of MSSA at concentrations less than 50 micrograms/mL. Drugs A, B, and C induced more than 25% growth inhibition of MRSA at less than 50 μgrams/mL. Drugs A, B, and C are water soluble and have Log P values of 3.27, 3.47, and 2.63, respectively. Each drug showed zero violations of the Rule of 5 and having a predicted intestinal absorbance of more than 90%. The polar surface area of A, B, and C is less than 60 A2, which suggests effective penetration of the blood-brain barrier. Rate of skin penetration (Kp) for A, B, and C are determined to be 0.00940 cm/hour, 0.00752 cm/hour, and 0.00398 cm/hour, respectively. Calculated pKa values for A, B, and C indicates they will have zero percent ionization at pH 7.2 of blood, pH 7.35 of cerebral spinal fluid, pH 5.5 of duodenum, and pH 1.0 of stomach, a property that improves cell membrane permeability.
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