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.