Synthesis, characterization and toxicity studies of pyridinecarboxaldehydes and L-tryptophan derived Schiff bases and corresponding copper (II) complexes

Abstract

Schiff bases and their metal-complexes are versatile compounds exhibiting a broad range of biological activities and thus actively used in the drug development process. The aim of the present study was the synthesis and characterization of new Schiff bases and their copper (II) complexes, derived from L-tryptophan and isomeric (2-; 3-; 4-) pyridinecarboxaldehydes, as well as the assessment of their toxicity in vitro. The optimal conditions of the Schiff base synthesis resulting in up to 75-85% yield of target products were identified. The structure-activity relationship analysis indicated that the location of the carboxaldehyde group at 2-, 3- or 4-position with regard to nitrogen of the pyridine ring in aldehyde component of the L-tryptophan derivative Schiff bases and corresponding copper complexes essentially change the biological activity of the compounds. The carboxaldehyde group at 2- and 4-positions leads to the higher cytotoxic activity, than that of at 3-position, and the presence of the copper in the complexes increases the cytotoxicity. Based on toxicity classification data, the compounds with non-toxic profile were identified, which can be used as new entities in the drug development process using Schiff base scaffold.

The radioenhancement potential of Schiff base derived copper (II) compounds against lung carcinoma in vitro

“…It has been shown that there is a dysregulation of copper homeostasis and/or localization in the organism affected by cancer [51,52]. Therefore, copper (II) complexes have received increasing attention for their biological characteristics [10,31,[53][54][55][56][57]. The development of copper-based metal complexes may promise an alternative to the adverse effects and toxicities seen in the traditionally used chemotherapy agent [10,31,[53][54][55][56][57].…”

“…The synthesis and characterization of Schiff base copper complexes have been carried out according to previously described methods [31]. All synthesis procedures were performed under normal atmospheric conditions.…”

“…In our previous work, we reported about the synthesis, structural characterization and toxicity of several Schiff bases and their copper complexes. It has been found that these compounds demonstrate high antiradical/antioxidant activity, stimulate the activities of enzymes of endogenous antioxidant defense systems and regulate the levels of biomarkers of the organism's immune system, demonstrating anti-inflammatory and immunomodulatory effects [31][32][33][34][35].…”

Effects of Schiff base aromatic amino acid derivatives on antioxidant and immune system disturbances in a rat model of aflatoxin B1 induced experimental mycotoxicosis

“…The synthesis of PLT was performed as described previously 17 by condensation of picolinaldehyde (2-pyridinecarboxaldehyde) and potassium salt of L-tryptophan in alcohol solution (ethanol, methanol) in a molar ratio 1:1 at the temperature range 5-25°C. A similar procedure was used for NLT synthesis, which is a condensation product of nicotinaldehyde (3-pyridinecarboxaldehyde) and L-tryptophan potassium salt, and PLP, which is a condensation product of picolinaldehyde (2-pyridinecarboxaldehyde) and L-phenylalanine potassium salt (Figure 1).…”

“…Our previous studies have demonstrated that Schiff base amino acid derivatives picolinyl-L-phenylalaninate (PLP), picolinyl-L-tryptophanate (PLT) and nicotinyl-L-tryptophanate (NLT) are capable of scavenging free-radicals, elevating the capacities of antioxidant and the immune system in radiation injury, and possessing anticytotoxic, antigenotoxic and antimutagenic properties 16,17 . Based on these results, we suggest that the abovementioned multifunctional compounds may have protective effects against mycotoxins.…”