Anti-inflammatory Potential of 1,4-Naphthoquinone Acyl Thiourea Hybrids on Lipopolysaccharide-Activated Mammalian Macrophages, and Their Acid Dissociation Constants

摘要

In this study, seven new and known 1,4-naphthoquinone acyl thiourea hybrids were synthesized and their molecular structures were confirmed by various analytical methods. These derivatives were tested for their anti-inflammatory potential on the murine macrophages. Pro-inflammatory cytokine production levels and cell viabilities were compared between the groups and with LPS positive control groups to determine the most potent anti-inflammatory drug candidate. Our results suggest that these derivatives had anti-inflammatory activity without exerting major cytotoxicity. Their future evaluation in inflammatory and autoimmune disease settings will be crucial for their possible utilization in the clinical setting. The acid dissociation constants of synthesized hybrids 1-7 were determined potentiometrically at 25.0 +/- 0.1 degrees C, at an ionic strength of 0.1 M NaCl in 20 (v/v) DMSO - water hydro-organic solvent mixture in an acidic medium. Three acid dissociation constants were calculated for each hybrid with the HYPERQUAD computer program using the data obtained as a result of potentiometric titrations under the specified conditions.