The Evaluation of the Anti-Histone Deacetylase, Antibacterial, Antioxidant and Cytotoxic Activities of Synthetic N,N´-ethylenebis (α methylsalicylideneiminate) Schiff Base Derivatives

Recently, Schiff base complexes as synthetic antioxidants are widely used instead of natural antioxidants because they are effective and cheaper. In this study, a series of α,ά-Me2-salen, (N,N´-ethylenebis(α methylsalicylideneiminate)) Schiff base derivatives have been investigated for their anti-histone deacetylase (HDAC), anticancer, antibacterial, and antioxidant activities. For anti-HDAC studies, AUTODOCK 4.1 and Molecular Dynamics (MD) simulations have been conducted against these combinations. Cytotoxic test, the ferric reducing ability of plasma (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) ABTS assays and Agar diffusion method have been applied to investigate anticancer, antioxidant and antibacterial activities, respectively. Based on the results, the best docking was obtained for α,ά-Me2-salen against HDAC. Also, MD calculation results demonstrated that the α,ά-Me2-salen is a more effective compound for HDAC inhibiting than SAHA as a known enzyme inhibitor. However, α,ά-Me2-salen, and its derivatives didn't display antibacterial activity against any of the microorganisms. Cytotoxic activity analysis toward MCF 7 cell line was apparent that α,ά-Me2-salen and its Ni (II), Co (II), and Cu (II) derivatives manifested high cytotoxic activity with IC50 5, 2, 2, and 3 µg/mL, respectively. The antioxidant results revealed excellent radical scavenging activities of all these compounds against DPPH, ABTS, and FRAP radicals. The antioxidant activity by DPPH, showed Mn(II) complex (IC50 = 0.13 ± 0.50 mg/mL) was the most active. While, α,ά-Me2-salen (IC50 =0.05±0.003 mg/mL) and its Ni(II) derivative (IC50 =0.049 mg/mL) exhibited the highest ABTS scavenging activity. According to the results, all compounds show acceptable anticancer and antioxidant activity and can be used as drug candidates after further investigations.