Sulfonamide agents for treatment of Staphylococcus MRSA and MSSA infections of the central nervous system.
For drugs that target the central nervous system (CNS) the penetration of the blood-brain barrier (BBB) is a necessity, whereas for other drugs it is an unwanted side-effect. Infections by Staphylococcus aureus (SA) of the CNS causes brain abscesses and inflammation of the tissue enclosing the brain and spinal cord. In this study four sulfonamide agents are compared to streptomycin for growth inhibition of SA bacteria in vitro. All sulfonamide agents were synthesized using microwave irradiation techniques. All drugs tested show substantial growth inhibition of MRSA and MSSA types of Staphylococcus aureus. Important pharmacological properties of streptomycin and sulfonamide drugs are determined to evaluate the efficacy for CNS targeting in clinical treatment of MSSA and and MRSA infections. Although streptomycin demonstrated considerable inhibition of MSSA and MRSA bacteria, the Log P value of -5.28 and polar surface area (PSA) of 331.4 Angstroms(2) effectively inhibits its penetration into the CNS. The Log BB for streptomycin at -4.756 also indicates a very unlikely candidate to treat SA infections of the CNS. All sulfonamide agents showed significant growth inhibition of MRSA and MSSA while having useful values of Log P and PSA for penetrating the BBB. In addition the Log BB values for each sulfonamide agent indicates these agents will enter the CNS to halt SA infections. The Log BB values for sulfonamide drugs 2, A, B, and C are -1.658, -0.109, -0.109, and -0.243, respectively. Values for Log P were 2.549, 3.27, 3.47, and 2.63, respectively; with PSA values at 137.8 A(2), 40.98 A(2), 40.98 A(2), and 49.36 A(2), respectively. The small size of the sulfonamide agents and other physicochemical properties strongly support the contention they can be effectively applied to treat MRSA and MSSA infections of the brain and spinal cord.
Chemistry Department, University of Nebraska, Omaha, 68182, USA. rbartzatt@mail.unomaha.edu
Ronald
R
Bartzatt
Suat Luan Go
SL
Cirillo
Jeffrey David
JD
Cirillo
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000187:drug effects; D002470:Cell Survival; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013307:Streptomycin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D013449:Sulfonamides; D013307:Streptomycin