Design, Synthesis and Multitarget Biological Evaluation of Perfluoroalkylated Benzoylthiourea Compounds: From Biofilm Disruption to DNA Cleavage

In the present study, a series of benzoylthiourea compounds bearing a perfluorinated group (-C₈F₁₇), namely <i>N</i>-((4-(heptadecafluorooctyl)-phenyl)-carbamothioyl)-benzamide (1) and <i>N</i>-((3-(heptadecafluorooctyl)-phenyl)-carbamothioyl)-benzamide (2) along with their non-fluorinated analogue, <i>N</i>-(phenylcarbamothioyl)-benzamide (3), were synthesized and characterized. Subsequently, various biological properties of the thiourea derivatives 1, 2, and 3 were evaluated, with a particular focus on elucidating the effect of the fluorinated group. The free radical scavenging activities of these compounds were evaluated with ascorbic acid and Trolox standards. Antioxidant activity peaked at 84.56% for 1 and 74.22% for 3. While 1 and 2 showed 97.70 and 96.50% inhibitory effects on α-amylase at 6.25 mg/L, 3 demonstrated 74.90% inhibitory effect at 100 mg/L. All compounds also displayed effective DNA nuclease activity. Additionally, antimicrobial and antibiofilm activities of benzoylthiourea compounds were also investigated. The most resistant microorganisms to the tested compounds were found to be <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>. In contrast, the most sensitive microorganisms were found to be <i>Legionella pneumophila</i> subsp. <i>pneumophila</i> and <i>Enterococcus faecalis</i>. The biofilm formation inhibition activities of benzoylthiourea compounds against <i>S. aureus</i> were 71.79, 69.80, and 63.53%, and against <i>P</i>. <i>aeruginosa</i> were 53.52, 63.33, and 70.00%, respectively, at the highest concentration. These findings provide a basis for proposing perfluorinated benzoylthiourea derivatives as potential potent, selective, and multitarget medicinal agents.