ABSTRACT
In the search for new drugs, strategies such as bioisosterism have been evidenced, in which the modification of molecules is already known to be active. Thus, metal complexes of known drugs have been highlighted, with examples of significant improvements in therapeutic efficacy. In this way, this work aimed at the synthesis of new zinc complexes with nonsteroidal anti-inflammatory drugs (NSAIDs), as well as the chemical characterization and the previous toxicity by cytotoxicity with Artemia salina, and evaluating the ability of these compounds to interact with DNA. As result, two new zinc II ternary complexes containing the NSAIDs diclofenac (Diclof) and ibuprofen (Ibup) and nicotinamide neutral linker (Nic) were obtained by the two-step solvent metal-ligand complexation method. Molecular structures were determined by NMR, FTIR, HR-MS, UV-Vis and X-ray diffraction, which demonstrated that both complexes are binuclear systems of general formula [Zn2(R-COO-)4(Nic)2]. Plasmidial DNA breakdown capacities were evaluated by producing single and double breaks (DNA FII and FIII) from plasmid incubation with complex solutions in the concentration range 0 to 400 µmol·L-1 in experiments with the presence and absence of light. Both experiments did not show significant differences (P ≤ 0.05) in induced DNA cleavage activity between the maximum study concentrations (400 µmol·L-1) and the negative controls for both complexes. The types of complex 1 and 2 interactions with the secondary DNA structure were determined by titrating a CT-DNA solution with complex solutions and monitored by circular dichroism spectrometry. The results showed that both complexes interact with the grooves of the secondary structure of CT-DNA by electrostatic attraction, but without evidence of alteration in the primary structure. Acute toxicity tests against Artemia salina showed that both complexes did not produce lethality >10% of the population up to a maximum concentration of 1200 µg·mL-1 within an exposure interval of 24 h. Thus, two new compounds were synthesized, characterized and had their previous toxicities determined. These compounds are promising new drugs, with the next step being evaluations of their activity.
Subject(s)
Artemia/growth & development , Coordination Complexes/toxicity , Cyclooxygenase Inhibitors/toxicity , Diclofenac/chemistry , Ibuprofen/chemistry , Niacinamide/chemistry , Zinc/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal , Artemia/drug effects , Coordination Complexes/chemistry , Crystallography, X-Ray , Cyclooxygenase Inhibitors/chemistry , DNA Cleavage , Molecular Structure , Toxicity Tests, AcuteABSTRACT
By-products of the grape juice industry contain valuable compounds. The current work produced bioactive-enriched extracts from by-products of the grape juice, through three different extraction methods. Yields and chemical compositions varied, according to the extraction method (ultrasound, microwave, liquid-liquid). High-efficiency liquid chromatography with UV-Vis and high-resolution mass spectrometry characterised were used for chemical characterization, with glycosylated flavonoids evident. The crude extract was fractionated by open column, which has possibility carried-out fraction rich in resveratrol. The inhibition of DPPH radicals ranged from 14.2 to 74.2%, and the total phenolic content ranged from 0.1 to 107.0 mg gallic acid equivalents/100 g. Microwave-assisted extraction of grape juice by-products using polar solvents, such as ethanol and water, provided the best yield and chemical composition, obtaining extracts rich in flavonoids. In this way, this work has demonstrated the industrial grape by-products importances, which are a rich source of antioxidants if properly extracted.
