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

Abstract

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 °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.

Exploring the latest trends in chemistry, structure, coordination, and diverse applications of 1-acyl-3-substituted thioureas: a comprehensive review

“…From these analyses it was concluded that the seven acyl thiourea exhibit potent anti-inflammatory activity and activity was found dose-dependent, thus by increasing the concentration, the anti-inflammatory activity of the acyl thiourea increases. 22 …”

“…N -substituted- N -acyl thioureas appear as key building blocks for generating various heterocyclic products through cyclization, 8,9 as well as serving as precursors for anion receptors, 10,11 organocatalysts, 12–14 corrosion inhibitors 15 and non-ionic surfactants. 16 Comprehensive research has documented the wide range of pharmacological benefits associated with acyl thiourea derivatives, including their potential as anticonvulsant, 17 anticancer, 18–20 antidiabetic, 21 anti-inflammatory, 22,23 anti-HIV, 24 antimicrobial, 25,26 urease inhibitory, 27 herbicidal, 28 and insecticidal agents. 29…”

Synthesis, Spectral Characteristics, and Molecular Docking Studies of 2-(2,4-Dichlorophenoxy)-N-(2,2,2-trichloro-1-(3-arylthioureido)ethyl)acetamide

“…Several other substances are also known to have anti-inflammatory activity and contain a 2,4-dichlorophenoxy group as a pharmacophore [3][4][5]. Alkylamide [6][7][8][9] and thiourea [10][11][12] fragments can also be distinguished among the pharmacophore groups with potential anti-inflammatory activity.…”