Novel benzoylthiourea derivatives had differential anti-inflammatory photodynamic therapy potentials on in vitro stimulated mammalian macrophages

• Published in: Photodiagnosis and photodynamic therapy 2022-03, Vol.37, p.102685-102685, Article 102685
• Main Authors: Emen, Fatih M., Kutlu, Emine, Karacolak, Ali I., Ali, Muhammad A., Demirdogen, Ruken E., Yesilkaynak, Tuncay, Erat, Selma, Ayaz, Furkan
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-inflammatory compounds; Aroylthiouurea; Benzoylthiourea; Crystallography, X-Ray; Inflammation; Macrophages; Photochemotherapy - methods; Photodynamic therapy; Spectroscopy, Fourier Transform Infrared
• ISSN: 1572-1000; 1873-1597
• DOI: 10.1016/j.pdpdt.2021.102685

•Different thiourea derivatives with PDT potentials were synthesized.•They all lacked anti-inflammatory activity in dark conditions.•Only one of them exerted potent anti-inflammatory activity upon illumination.•It exerted this activity in subtoxic concentration. Novel benzoylthioureas, N-((5-chloropyridin-2yl)carbamothioyl)benzamide, (HL1), N-((2-chloropyridin-3yl)carbamothioyl)benzamide, (HL2), N-((5-bromopyridin-2yl)carbamothioyl)benzamide, (HL3) and N-(Naphthalene-1-yl(phenyl)carbamothioyl)benzamide, (HL4), were synthesized. Their characterizations were made by FT-IR,1H NMR and 13C NMR spectrophotometric analysis. Single crystal X-ray diffraction measurements were conducted to determine the crystal structure of HL1 and HL4.  The HL1 crystallization conditions are: in the monoclinic crystal system with P21/c space group, Z = 2, a = 8.118(2) Å, b = 12.056(3) Å, c = 13.753(4) Å. HL4crystallization conditions are: in the orthorhombic crystal system with Pbca space group, Z = 8, a = 19.597(9) Å, b = 8.270(4) Å, c = 24.299(11) Å. Investigation of photodynamic and antiinflamatory effects of these compounds revealed that they are potent adducts. Using these derivatives, mammalian macrophages were stimulated with LPS to test their anti-inflammatory activity. Based on pro-inflammatory cytokine production levels, the photodynamic anti-inflammatory activity of these adducts were found to differ. Our results showedthat benzoylthioureas can be used as potential photodynamic therapy agents to suppress the excessive inflammatory reactions encountered in autoimmune and inflammatory disorders. [Display omitted]