Spectroscopic and theoretical investigation of the potential anti-tumor and anti-microbial agent, 3-(1-((2-hydroxyphenyl)amino)ethylidene)chroman-2,4-dione.

The coumarin-orthoaminophenol derivative was prepared under mild conditions. Based on crystallographic structure, IR and Raman, 1H and 13C NMR spectra the most applicable theoretical method was determined to be B3LYP-D3BJ. The stability and reactivity parameters were calculated, in the framework of NBO, QTAIM and Fukui functions, form the optimized structure. This reactivity was then probed in biological systems. The antimicrobial activity towards four bacteria and three fungi species was examined and activity was proven. In vitro cytotoxic effects, against human epithelial colorectal carcinoma HCT-116 and human healthy lung MRC-5 cell lines, of the investigated substance are also tested. Compound showed significant cytotoxic effects on HCT-116 cells, while on MRC-5 cells showed no cytotoxic effects. The effect of hydroxy group in ortho-position on the overall reactivity of molecule was examined through molecular docking with Glutathione-S-transferases.

Synthesis and Characterization of 3-(1-((3,4-Dihydroxyphenethyl)amino)ethylidene)-chroman-2,4-dione as a Potential Antitumor Agent.

The newly synthesized coumarin derivative with dopamine, 3-(1-((3,4-dihydroxyphenethyl)amino)ethylidene)-chroman-2,4-dione, was completely structurally characterized by X-ray crystallography. It was shown that several types of hydrogen bonds are present, which additionally stabilize the structure. The compound was tested in vitro against different cell lines, healthy human keratinocyte HaCaT, cervical squamous cell carcinoma SiHa, breast carcinoma MCF7, and hepatocellular carcinoma HepG2. Compared to control, the new derivate showed a stronger effect on both healthy and carcinoma cell lines, with the most prominent effect on the breast carcinoma MCF7 cell line. The molecular docking study, obtained for ten different conformations of the new compound, showed its inhibitory nature against CDKS protein. Lower inhibition constant, relative to one of 4-OH-coumarine, proved stronger and more numerous interactions with CDKS protein. These interactions were carefully examined for both parent molecule and derivative and explained from a structural point of view.

Synthesis, spectroscopic characterization (FT-IR, FT-Raman, and NMR), quantum chemical studies and molecular docking of 3-(1-(phenylamino)ethylidene)-chroman-2,4-dione.

The experimental and theoretical investigations of structure of the 3-(1-(phenylamino)ethylidene)-chroman-2,4-dione were performed. X-ray structure analysis and spectroscopic methods (FTIR and FT-Raman, 1H and 13C NMR), along with the density functional theory calculations (B3LYP functional with empirical dispersion corrections D3BJ in combination with the 6-311 + G(d,p) basis set), were used in order to characterize the molecular structure and spectroscopic behavior of the investigated coumarin derivative. Molecular docking analysis was carried out to identify the potency of inhibition of the title molecule against human's Ubiquinol-Cytochrome C Reductase Binding Protein (UQCRB) and Methylenetetrahydrofolate reductase (MTHFR). The inhibition activity was obtained for ten conformations of ligand inside the proteins.

Investigation of the antioxidant and radical scavenging activities of some phenolic Schiff bases with different free radicals.

The antioxidant properties of some phenolic Schiff bases in the presence of different reactive particles such as (•)OH, (•)OOH, (CH2=CH-O-O(•)), and (-•)O2 were investigated. The thermodynamic values, ΔH BDE, ΔH IP, and ΔH PA, were used for this purpose. Three possible mechanisms for transfer of hydrogen atom, concerted proton-electron transfer (CPET), single electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET) were considered. These mechanisms were tested in solvents of different polarity. On the basis of the obtained results it was shown that SET-PT antioxidant mechanism can be the dominant mechanism when Schiff bases react with radical cation, while SPLET and CPET are competitive mechanisms for radical scavenging of hydroxy radical in all solvents under investigation. Examined Schiff bases react with the peroxy radicals via SPLET mechanism in polar and nonpolar solvents. The superoxide radical anion reacts with these Schiff bases very slowly.

Influence of different free radicals on scavenging potency of gallic acid.

The M05-2X/6-311++G(d,p) and B3LYP-D2/6-311++G(d,p) models are used to evaluate scavenging potency of gallic acid. The hydrogen atom transfer (HAT), sequential proton loss electron transfer (SPLET), and single electron transfer followed by proton transfer (SET-PT) mechanisms of gallic acid with some radicals ((•)OO(-), (•)OH, and CH3OO(•)) were investigated using the corresponding thermodynamic quantities: bond dissociation enthalpy (BDE), ionization potential (IP), and proton affinity (PA). Namely, the ΔHBDE, ΔHIP, and ΔHPA values of the corresponding reactions in some solvents (water, DMSO, pentylethanoate, and benzene) are investigated using an implicit solvation model (SMD). An approach based on the reactions enthalpies related to the examined mechanisms is applied. This approach shows that a thermodynamically favored mechanism depends on the polarity of reaction media and properties of free radical reactive species. The most acidic 4-OH group of gallic acid is the active site for radical inactivation. The results of this investigation indicate that the SPLET mechanism can be a favored reaction pathway for all three radicals in all solvents, except for (•)OH in the aqueous solution. In water, gallic acid can inactivate (•)OH by the HAT mechanism.

Free radical scavenging activity of morin 2'-O(-) phenoxide anion.

Due to intramolecular H-atom transfer, deprotonation of the most acidic 3-OH group of morin yields 2'-O(-) phenoxide anion. The reaction enthalpies related to mechanisms of free radical scavenging activity of this dominant species at a physiological pH of 7.4 were calculated by PM6 and DFT methods in gas-phase, water, benzene and DMSO. Results indicate the 4'-OH group of 2'-O(-) phenoxide anion is the active site for radical inactivation. The thermodynamically favoured mechanism depends on the polarity of the reaction media: in polar solvents (water and DMSO), the sequential proton loss electron transfer (SPLET) mechanism is preferred while in non-polar benzene (and in gas-phase), the hydrogen atom transfer (HAT) mechanism is responsible for the free radical scavenging activity of the morin phenoxide anion. Results show that the fast, semiempirical PM6 method fairly mimics more accurate, though time-consuming DFT methodologies.

PM6 and DFT study of free radical scavenging activity of morin.

Flavonoids have long been recognised for their general health-promoting properties, of which their antioxidant activity may play an important role. In this work, we have studied the properties of flavonoid morin using semiempirical and density functional theory (DFT) methods in order to validate the application of the recently developed parametric method 6 (PM6). Reaction enthalpies related to mechanisms of free radical scavenging by flavonoid morin were calculated by DFT and PM6 methods in gas-phase, water, DMSO and benzene. It has been shown that fast semiempirical PM6 method can mimic results obtained by means of more accurate time consuming DFT calculations. Thermodynamically favoured mechanism depends on reaction medium: SPLET (sequential proton loss electron transfer) is preferred in water and DMSO, and HAT (hydrogen atom transfer) is predominant in gas-phase. In benzene these two mechanisms are competitive.