Humic acids: Structural properties and multiple functionalities for novel technological developments

The role of chronic hyperglycemia in the development of diabetic microvascular complications and in neuropathy has been clearly established by intervention studies. However, the biochemical or cellular links between elevated blood glucose levels, and the vascular lesions remain incompletely understood. This review focuses on the consequences of hyperglycemia on the formation of advanced glycation end-products (AGEs), and on the role of AGEs and of their specific receptors (RAGE) in the functional and anatomical alterations of the vascular wall. AGEs are formed during the Maillard reaction by the binding of aldoses on free NH(2) groups of proteins, which, after a cascade of molecular rearrangements, result in molecules of brown color and specific fluorescence. Experimental studies have indicated that the binding of AGEs to RAGE activates cells, particularly monocytes and endothelial cells. Activated endothelial cells produce cytokines, and express adhesion molecules and tissue factor. The role of AGEs in increased oxidative stress, and in the functional alterations in vascular tone control observed in diabetes, in part related to a reduction in nitric oxide, is also discussed. The microvascular retinal, glomerular and nerve lesions induced by experimental diabetes in animals are prevented by an inhibitor of AGEs formation, aminoguanidine. The administration in diabetic animals of recombinant RAGE, which hinders AGEs-RAGE interaction, prevents hyperpermeability and vascular lesions. These data suggest a central role of AGEs and RAGE in the development of chronic complications of diabetes.

Iconography : Advanced glycation end products, their receptors and diabetic angiopathy

A series of new 4-(3-(4-substitutedphenyl)-3a,4-dihydro-3H-indeno[1,2-c]pyrazol-2-yl) benzenesulfonamides (7-12) was synthesized starting from 2-(4-substitutedbenzylidene)-2,3-dihydro-1H-inden-1-one (1-6) and 4-hydrazinobenzenesulfonamide. The substituted benzaldehydes from which the key intermediate was prepared by introducing 2- or 4-substituents such as fluorine, hydroxy, methoxy, or the 3,4,5-trimethoxy moieties. The compounds were tested for their cytotoxicity, tumor-specificity and potential as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The 3,4,5-trimethoxy and the 4-hydroxy derivatives showed interesting cytotoxic activities, which may be crucial for further anti-tumor activity studies, whereas some of these sulfonamides strongly inhibited both human (h) cytosolic isoforms hCA I and II.

https://www.tandfonline.com/doi/pdf/10.3109/14756366.2016.1160077

Synthesis and bioactivity studies on new 4-(3-(4-Substitutedphenyl)-3a,4-dihydro-3H-indeno[1,2-c]pyrazol-2-yl) benzenesulfonamides.

The Photorhabdus temperata M1021 secretes toxic compounds that kill their insect hosts by arresting immune responses. Present study was aimed to purify the insecticidal and antimicrobial compound(s) from the culture extract of P. temperata M1021 through bioassay guided fractionation. An ethyl acetate (EtOAc) extract of the P. temperata M1021 exhibited 100% mortality in Galleria mellonella larvae within 72 h. In addition, EtOAc extract and bioactive compound 1 purified form the extract through to column chromatography, showed phenol oxidase inhibition up to 60% and 80% respectively. The analysis of (1)H and (13)C NMR spectra revealed the identity of pure compound as "benzaldehyde". The benzaldehyde showed insecticidal activity against G. mellonella in a dose-dependent manner and 100% insect mortality was observed at 108 h after injection of 8 mM benzaldehyde. In a PO inhibition assay, 4, 6, and 8 mM concentrations of benzaldehyde were found to inhibit PO activity about 15%, 42%, and 80% respectively. In addition, nodule formation was significantly (P < 0.05) inhibited by 4, 6, and 8 mM of benzaldehyde as compare to control. Moreover, benzaldehyde was found to have great antioxidant activity and maximum antioxidant activity was 52.9% at 8 mM benzaldehyde as compare to control. Antimicrobial activity was assessed by MIC values ranged from 6 mM 10 mM for bacterial strains and 8 mM to 10 mM for fungal strains. The results suggest that benzaldehyde could be applicable for developing novel insecticide for agriculture use.

Benzaldehyde as an insecticidal, antimicrobial, and antioxidant compound produced by Photorhabdus temperata M1021.

Flavonoids, a group of phenolic compounds found naturally in fruit, vegetables, nuts, flowers, seeds and bark are an integral part of the human diet. They have been reported to exhibit a wide range of biological effects, including antiischemic, antiplatelet, antineoplastic, antiinflammatory, antiallergic, antilipoperoxidant or gastroprotective actions. Furthermore, flavonoids are potent antioxidants, free radical scavengers and metal chelators, and inhibit lipid peroxidation. Oxidative modification of low-density lipoproteins (LDLs) is believed to play a crucial role in atherogenesis. Epidemiological studies have shown that the consumption of fruits and vegetables, and regular red wine consumption is related with a reduced risk of cardiovascular diseases.

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Dietary flavonoids and risk of coronary heart disease.

Antioxidant properties of benzoic acid derivatives against superoxide radical

Humic acids are known for their overall positive health and productivity effects in animal feeding trials and, controversially, as an aetiological factor of cancer. We tried to assess the in vitro effect of humic acids from a selected source in Slovakia when used at recommended prophylactic dosage. We investigated antioxidant properties, enzymatic and non-enzymatic antioxidant defence system in liver mitochondria and cultured cancer cell lines in vitro. We observed a significant decrease in superoxide dismutase activity after humic acids treatment irrespective of dissolving in dimethyl sulphoxide or direct addition to mitochondria suspension in a respiration medium. Activities of other antioxidant enzymes measured, such as glutathione peroxidase and glutathione reductase, showed no significant differences from the control as well as the reduced glutathione content. Percentage of inhibition by humic acids of superoxide radical indicated lower efficacy compared with that of hydroxyl radical. Survival of six different cancer cells lines indicated that only the acute T lymphoblastic leukaemia cell line was sensitive to the tested humic acids. Despite relatively low solubility in aqueous solutions, humic acids from the selected source participated in redox regulation. By recapturing the radicals, humic acids reloaded the antioxidant defensive mechanism. Results from in vitro study conducted with humic acids from the natural source showed potential of these substances as promising immunity enhancing agents.

Effects of humic acids in vitro.

UV–vis and fluorescence spectroscopic investigations of chalcones and cyclic chalcone analogues, (E)-2-(4-X-benzylidene)-1-indanones, -tetralones, and -benzosuberones with the same substitution patterns were performed in solvents with different polarity. Comparison of position of the absorption maxima of three substituted series (unsubstituted, methoxy, and dimethylamino) showed the same decreasing order indanones ≥ chalcones ≥ tetralones ≥ benzosuberones in each solvent indicating the strongest conjugation of the rigid, planar indanones. All the compounds showed positive solvatochromism, which is consistent with transitions having significant charge transfer character. The order of the observed solvent-induced bathochromic shifts of the absorption maxima was found to correlate with the donor number of the solvents. The solvent-induced shift of the emission maxima of each compound is larger than that of the absorption maxima. Recording the UV–vis spectra of the compounds in the presence of bovine and human serum albumin resulted in a slight hypsochromic shift of (E)-2-(4-methoxybenzylidene)- and (E)-2-[(4-dimethylamino)benzylidene]benzosuberone indicating changing the polar environment to a less polar one. Such an observation is in accord with an interaction of the molecules with the hydrophobic binding site(s) of the two proteins.

(E)-2-Benzylidenecyclanones: Part VI. Solvent effect on the UV and fluorescence properties of some chalcones and their cyclic analogues. Interaction of 4-dimethylaminochalcones with bovine and human serum albumin: a UV–vis study

UV–Vis spectrophotometry was used to determine acid dissociation constant (pK
 a) values of the natural flavonoids phloretin, phlorizin, naringenin, and naringin, as well as 4′-hydroxychalcone, 4′-(dimethylamino)chalcone, and their cyclic analogues. Comparison of the results with those previously reported for the natural flavonoids showed the applied method is a relatively straightforward and easy-to-perform technique for the determination of pK
 a values of compounds with relatively low solubility. Comparative analysis of the pK
 a values of the synthetic chalcones showed a strong correlation between the degree of conjugation and the acid strength of the respective compounds with different geometry. Our results provide further evidence that modification of the three-dimensional structure of open-chain bioactive compounds is the method of choice to modify not only their stereochemistry but also their physicochemical properties.

(E)-2-Benzylidenebenzocyclanones, part VIII: spectrophotometric determination of pK a values of some natural and synthetic chalcones and their cyclic analogues

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Ivan Kron

Papers

Antioxidant properties of benzoic acid derivatives against superoxide radical

Effects of humic acids in vitro.

(E)-2-Benzylidenecyclanones: Part VI. Solvent effect on the UV and fluorescence properties of some chalcones and their cyclic analogues. Interaction of 4-dimethylaminochalcones with bovine and human serum albumin: a UV–vis study

(E)-2-Benzylidenebenzocyclanones, part VIII: spectrophotometric determination of pK a values of some natural and synthetic chalcones and their cyclic analogues

Oxidative Processes and Antioxidative Metaloenzymes