New aryl Schiff bases of thiadiazole derivative of ibuprofen as DNA binders and potential anti-cancer drug candidates
Creators: name: Farooqi, Shahid Iqbal
name: Arshad, Nasima
name: Pervaiz Ali Channar
name: Perveen, Fouzia
name: Aamer Saeed
name: Fayaz Ali Larik
name: Aneela Javed
name: Maham Yamin
Publisher: name: Taylor & Francis
Year: 2020
Subjects: subject: Biophysics
subject: Biochemistry
subject: Space Science
subject: 29999 Physical Sciences not elsewhere classified
subject: FOS: Physical sciences
subject: FOS: Physical sciences
subject: Cell Biology
subject: Molecular Biology
subject: Pharmacology
subject: Biotechnology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: Cancer
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: FOS: Health sciences

description: The work presented in this paper describes the synthesis of two new aryl Schiff bases [(<i>E</i>)-<i>N</i>-(4-(benzyloxy)-3-methoxybenzylidene)-5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine] (ASB-1) and [(<i>E</i>)-<i>N</i>-(4-(benzyloxy)benzylidene)-5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine] (ASB-2). These compounds were characterized by different analytical techniques and then studied for DNA binding. Binding studies were carried out at neutral pH (7.0) and at 37 °C by theoretical and experimental methods including DFT, molecular docking, spectroscopy (UV-visible, fluorescence), cyclic voltammetry (CV) and viscometry. Further investigations of these compounds were done on hepatocellular carcinoma; Huh-7 cancer cell line. Binding constant, free energy change and binding site size i.e., K<sub>b</sub>, ΔG, and n were evaluated which indicated that both ASB-1 and ASB-2 bind significantly and spontaneously with the DNA. However, data revealed relatively greater binding of ASB-1 with DNA. Spectral and voltammetric results were found supportive of each other. Binding site sizes and viscosity measurements verified the mixed binding mode of interactions as observed in molecular docking analysis i.e., intercalation with groove binding. DNA binding studies were very well correlated with the in-vitro studies performed on Huh-7 cell line as well as normal HEK-293 cell lines. The compound ASB-1 not only showed greater binding affinity towards DNA but also showed greater anti-cancer potency with least IC<sub>50</sub> value as compared to ASB-2. Highlights:New aryl Schiff bases of thiadiazole derivative of ibuprofen ASB-1 &amp; 2Reactivity and mixed binding mode of interaction with DNA by DFT and dockingGood agreements in the binding parameters by spectroscopy and voltammetryK<sub>b</sub>, ΔG and n determined greater for ASB-1indicating its stronger binding with DNAGreater anticancer potential of ASB-1against Huh-7 cell line New aryl Schiff bases of thiadiazole derivative of ibuprofen ASB-1 &amp; 2 Reactivity and mixed binding mode of interaction with DNA by DFT and docking Good agreements in the binding parameters by spectroscopy and voltammetry K<sub>b</sub>, ΔG and n determined greater for ASB-1indicating its stronger binding with DNA Greater anticancer potential of ASB-1against Huh-7 cell line