Design, synthesis and biological evaluation of ethyl-4,4,4-trifluoro-3-hydrazonobutanoate derivatives

• Published in: Journal of molecular structure 2022-02, Vol.1250, p.131705, Article 131705
• Main Authors: Saadaoui, Ikram, Jismy, Badr, Salah, Bochra Ben, Miled, Nabil, Alghamdi, Othman A., Bougatef, Hajer, Bougatef, Ali, Kossentini, Mohamed, Abarbri, Mohamed
• Format: Article
• Language: English
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.131705

•Efficient synthesis of novel ethyl 4,4,4-trifluoro-3-hydrazonobutanoate derivatives•Anti-hypertensive effect of these compounds was observed•The new synthesized structures can be considered of interest for further modification as antioxidant and antibacterial agents.•The methodology developed represents a flexible and efficient approach opening the way to the possibility of constructing a new chemical library of variously substituted fluorinated hydrazonobutanoate of biological interest. [Display omitted] The present study describes the synthesis and biological investigation of novel ethyl 4,4,4-trifluoro-3-hydrazonobutanoate derivatives, which were synthesized by condensation of commercially available hydrazines and ethyl 4,4,4-trifluorobut-2-ynoate. We explored the chemical space of these new fluorinated compounds to determine their antioxidant and antibacterial activities and their angiotensin I-converting enzyme (ACE) inhibition ability. The results indicated that the seven compounds synthesized revealed excellent antioxidant activity with inhibition values in the range of 67.83 ± 0.001-95.77 ± 0.05% at 2 µM. The compound 3g displayed the highest ACE inhibitory activity with an IC50 of 2.42 µM. The results revealed also that compound 3e was highly active against S. typhi, L. monocytogenes and K. pneumoniae. The docking of chemical compounds in the ACE active site showed possible inhibitory effect of all compounds on the catalytic activity of the enzyme, which would satisfactorily explain the anti-hypertensive effect of these compounds.