Synthesis, biological evaluation and docking study of 3-aroyl-1-(4-sulfamoylphenyl)thiourea derivatives as 15-lipoxygenase inhibitors

• Published in: European journal of medicinal chemistry 2014-07, Vol.82, p.308-313
• Main Authors: Mahdavi, Mohammad, Shirazi, Maryam Shahzad, Taherkhani, Raana, Saeedi, Mina, Alipour, Eskandar, Moghadam, Farshad Homayouni, Moradi, Alireza, Nadri, Hamid, Emami, Saeed, Firoozpour, Loghman, Shafiee, Abbas, Foroumadi, Alireza
• Format: Article
• Language: English
• Subjects: 15-Lipoxygenase; Animals; Antioxidant activity; Arachidonate 15-Lipoxygenase - metabolism; Cell Death - drug effects; Cell Differentiation - drug effects; Cell Survival - drug effects; Cells, Cultured; Docking study; Dose-Response Relationship, Drug; Enzyme inhibitors; Glycine max - enzymology; Hydrogen Peroxide - antagonists & inhibitors; Hydrogen Peroxide - pharmacology; Lipoxygenase Inhibitors - chemical synthesis; Lipoxygenase Inhibitors - chemistry; Lipoxygenase Inhibitors - pharmacology; Models, Molecular; Molecular Structure; Oxidative Stress - drug effects; PC12 Cells; Rats; Structure-Activity Relationship; Sulfonamides; Thiourea
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.05.054

A series of 3-aroyl-1-(4-sulfamoylphenyl)thiourea derivatives containing sulfonamide moiety were designed and synthesized as 15-lipoxygenase (15-LOX) inhibitors. Most synthesized compounds showed potent activity against soybean 15-LOX with IC50 values less than 25 μM. The most potent compound 4c (3-methylbenzoyl derivative) with IC50 value of 1.8 μM was 10-fold more potent than quercetin. Interestingly, compound 4c also showed the highest antioxidant activity, as determined by ferric reducing antioxidant power (FRAP) assay. Its capacity for reducing ferric ion was more than ascorbic acid. The viability assay of the selected compound 4c against oxidative stress-induced cell death in differentiated PC12 cells revealed that compound 4c significantly protected neurons against cell death in low concentrations. A series of thiourea derivatives containing sulfonamide moiety were designed and synthesized as 15-lipoxygenase (15-LOX) inhibitors. The most potent compound 4c (3-methylbenzoyl derivative) with IC50 value of 1.8 μM was 10-fold more potent than quercetin. [Display omitted] •A series of thiourea containing sulfonamide moiety were synthesized.•The thiourea derivatives showed 15-lipoxygenase (15-LOX) inhibitory activity.•Compound 4c (IC50 = 1.8 μM) was 10-fold more potent than quercetin.