Exploring the structure-activity relationship (SAR) of Schiff bases as effective compounds in scavenging free radicals

•Two Schiff base derivatives synthesized from 2‑hydroxy-1-naphthaldehyde were synthesized.•DFT calculations show that 1 is more stable as an enol tautomer, while 2 is a keto.•The free radical scavenging potential of 1 and 2 was studied by DPPH and ABTS assay.•The SAR evaluation also included Schiff...

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Bibliographic Details
Published in:	Journal of molecular structure Vol. 1315; p. 138729
Main Authors:	Nunes, Ianka J., Dias, Renieidy F.C., da Silva, Alecia F., Ferreira, Wesley V., Cunico, Wilson, Couto, Gabriel T., Bianchini, Daniela, Casagrande, Osvaldo de L., Saffi, Jenifer, Pinheiro, Adriana C.
Format:	Journal Article
Language:	English
Published:	Elsevier B.V 05-11-2024
Subjects:	ADMETox studies Cytotoxicity DFT calculations Scavenging activity Schiff-base compounds Structure-activity relationship (SAR) Scavenging activity Cytotoxicity Structure-activity relationship (SAR) Schiff-base compounds ADMETox studies DFT calculations
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Summary:	•Two Schiff base derivatives synthesized from 2‑hydroxy-1-naphthaldehyde were synthesized.•DFT calculations show that 1 is more stable as an enol tautomer, while 2 is a keto.•The free radical scavenging potential of 1 and 2 was studied by DPPH and ABTS assay.•The SAR evaluation also included Schiff base derivatives of tert‑butylphenol.•The cytotoxicity in mammalian cells was investigated. Naphthol-imine compounds containing N-phenylethylenediamine (1) and quinoline amine (2) moieties were synthesized and characterized. Density Functional Theory (DFT) calculations were performed aiming to obtain information on the chemical properties of these molecules. In silico ADME/Tox profile analyses were performed on molecules 1 and 2 using the web tools pkCSM-pharmacokinetics, Molinspiration, and Osiris Property Explorer. Drug-likeness levels of 1 and 2 were predicted according to the Lipinski rules. The radical scavenger activity of compounds 1 and 2 was determined by in vitro assays such as 1,1-diphenyl-2-picrylhydrazyl free radicals (DPPH.) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radicals (ABTS.+). Molecules 1 and 2 were ineffective as radical scavengers in the DPPH radical capture assay at the test doses. However, 1 showed activity in eliminating ABTS+ radical with IC50 = 17.4 ± 0.9 µM. The neutral red assay determined the cytotoxicity of 1 and 2 against the V79 cell line. Molecule 1 was more cytotoxic than 2, with IC50 values of 36.67 µM and 51.26 µM, respectively. The alkaline comet assay was used to investigate the in vitro genotoxicity of 1 and 2. After 24 h of exposure to a dose of 20 μM, 1 did not cause significant DNA damage compared to non-exposed cells. The compounds were tested for toxicity using Artemia saline assay. [Display omitted]
ISSN:	0022-2860
DOI:	10.1016/j.molstruc.2024.138729