It was shown that benzyltrimethylammonium tribromide is a convenient reagent for the synthesis of bromo derivatives of 2-isobornylphenols and natural phenolic compounds, viz., thymol and carvacrol. The use of this reagent allows synthesizing mono- and dihalogenated products bearing the substituents at the ortho- and/or para-positions.

2,6-Di-tert-butyl-4-methylphenol reacted with an equimolar amount of benzyltrimethylammonium tribromide to give 4-bromomethyl derivative but not 4-hydroxymethyl derivative as was reported earlier. The present work is devoted to the synthesis of 4-bromomethylphenols with bulky tert-butyl and/or isobornyl moieties at positions 2 and 6.

The data obtained earlier on the Mannich bases derived from natural and synthetic phenols are summarized, the structure—antioxidant activity relationship is analyzed, and the most active compounds among these bases are identified. The influence of the nature and position of aminomethyl substituents on the hemolytic activity (erythrotoxicity) is considered. The high antioxidant and membrane-protective activity exhibited by some Mannich bases in the model of oxidative hemolysis of mammalian erythrocytes is explained by the presence in their structure of a N -alkyl group or a fragment of a heterocyclic amine, which affects the lipophilicity of the compounds and the interaction with the cell membrane.

A series of symmetric methylenebisphenols based on sesamol (1), 2-methoxybenzene-1,4-diol (2), eugenol (3), carvacrol (4), and thymol (5) was synthesized using the condensation reaction between these phenols and paraformaldehyde. We carried out a comparative evaluation of the antioxidant properties of both parent compounds 1–5 and the products derived from them. The conversion of sesamol (1), eugenol (3), and thymol (5) to the corresponding methylenebisphenols is associated with a significant increase in the antioxidant activity (AOA) of the synthesized compounds, measured by the degree of inhibition of Fe2+/ascorbate-induced fatty acid oxidation of mouse brain lipids. The derivatives are superior to the original natural phenols in terms of their ability to improve the survival of red blood cells (RBCs) of lab mice and protect their hemoglobin from oxidation under the conditions of hemolysis induced by 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) or hydrogen peroxide. In terms of several parameters, the activity of the synthesized products exceeded that of the synthetic antioxidant 2,6-di-tert-butyl-4-methylphenol (BHT).

A series of novel Mannich bases containing (monomethoxy-, dimethoxy- or trimethoxy)phenyl substituent and morpholine fragment have been synthesized via C-4-monoaminomethylation of alpha-mangostin, a natural hydroxyxanthone. This modification has led to a considerable reduction in erythrotoxicity of natural xanthone while preserving its high antioxidant activity. All synthesized derivatives have demonstrated higher radical scavenging activity and total antioxidant activity compared to those of alpha-mangostin, several compounds have also shown higher efficacy in the test system with red blood cells. In the model of oxidative hemolysis of red blood cells induced by hydrogen peroxide and 2,2'-azobis(2-amidinopropane) dihydrochloride, a Mannich base containing 3,4,5-trimethoxyphenyl substituent has been shown to have the highest membrane-protective and antioxidant activity.

Reaction rate constants (k7) are measured for bis- and sulfur-containing isobornylphenols (IBPs) with peroxide radicals of ethylbenzene. The antioxidant activity of IBPs and the effect lecithin has on the effectiveness of their inhibitory action are studied using the model of methyl oleate autoxidation in a thin layer. It is established that introducing a sulfur atom into an IBP molecule reduces its antiradical activity. All studied compounds are characterized by a lower value of the constant k7, relative to the same value for 4‑methyl-2,6-diisobornylphenol. The presence of lecithin in the reaction mixture reduces the efficiency of using bis- and mono-IBPs (including IBPs with sulfur-containing substituents) when inhibiting the autoxidation of methyl oleate in a thin layer. An exception is IBP with an SH group, for which there is a slight increase in antioxidant activity. The observed differences in the effect lecithin on the reactivity of IBPs must be considered when assessing their biological activity.

We studied the effect of antioxidants dibornol (2,6-diisobornyl-4-methylphenol) and its derivative (4-hydroxymethyl-2,6-diisobornylphenol), members of the alkylated phenols group, on the redox potential of male germ cells and their morphological and functional state in the rat model of pathospermia. Pharmacological effect was observed in animals treated with dibornol. The studied compounds led to the normalization of the antioxidant-prooxidant balance. However, the value of this indicator against the background of treatment with dibornol derivative attested to a shift in the redox balance of cells towards reduction reactions.

A comparative evaluation of the antiviral activity of a number of new and previously synthesized terpenophenols and their N- or O-containing derivatives against the A/Puerto Rico/8/34 (H1N1) virus strain was carried out. 2-Isobornylphenol, 1,2-dihydroxy-6-isobornyl-4-methylbenzene, 2-isobornyl-1,4-benzoquinone, and N-butyl-4-hydroxy-3,5-diisobornylbenzamide showed the highest activity.

In this work, a series of C-3-aminomethyl derivatives based on alizarin (1) was obtained using Mannich reaction. The antioxidant properties of the compounds were evaluated using in vitro models. It was found that most of the synthesized derivatives were superior to alizarin (1) in radical scavenging activity and Fe2+-chelation ability. The antioxidant activity of alizarin derivatives was confirmed using biologically relevant test systems; all compounds strongly inhibited Fe2+/ascorbate-initiated oxidation of unsaturated fatty acids of animal lipids and most of them increased the survival of red blood cells under conditions of acute oxidative stress. In the cellular model system, the Mannich base containing a thiomorpholinomethyl moiety demonstrated the highest activity.

The reaction of o -isobornylphenols with bismuth( iii ) nitrate provided o - and p -nitrophenols, the reduction of the nitro group of which with zinc dust in acetic acid led to the corresponding o - and p -aminophenols. A comparative evaluation of antioxidant properties was performed for the newly obtained aminophenols with an isobornyl substituent using in vitro models. It is shown that the proposed modification of o -isobornylphenols is promising for obtaining new highly active inhibitors of oxidative processes.

Some new derivatives based on 2,6-diisobornylphenol and containing amine moieties of the pinane structure at the para-position relative to the phenolic hydroxy group were synthesized. The antioxidant properties of the obtained compounds were estimated using various in vitro models. The introduction of diamine moiety into a starting molecule led to a significant increase in the radical scavenging activity and the ability to chelate Fe2+ ions.

Several synthetic approaches (aminomethylation, alkylation, condensation, etc.) have been used to synthesize derivatives based on the sesamol (1), natural phenol. The set of methods, including the study of antioxidant activity (AOA) by the ability to inhibit the initiated oxidation of animal lipids, radical scavenging activity, Fe2+ -chelation ability, as well as a comparative assessment of membrane-protective activity under the conditions of H2 O2 -induced hemolysis of mice red blood cells (RBCs), was used to analyze the antioxidant potential of the synthesized compounds. The synthesized derivatives have demonstrated different activity in the listed test systems, and we have identified compounds which appear to be most promising for a detailed study of their pharmacological properties.

New derivatives of 2,6-diisobornylphenol containing (phenylamino)methyl or (benzylamino)methyl moiety, or heterocyclic (1H-benzo[d]imidazol-1-yl)methyl, (2-benzyl-1H-benzo[d]imidazol-1-yl)methyl, or (1H-benzo[d][1,2,3]triazol-1-yl)methyl substituent at the para-position relative to the hydroxy group were synthesized. A comparative evaluation of the antioxidant activity was carried out using in vitro models for the most of compounds obtained. The activity of synthesized derivatives depends on the test system used and, in some cases, may be related to a membrane stabilizing effect.

Introduction. Benign prostatic hyperplasia (BPH) is a common urological disorder in older men. It is characterized by the development of glandularstromal hyperplasia of the prostate with the formation of new glandular structures and subsequent symptoms from the lower urinary tract. It has now been established that the pathogenesis of this disease is multifactorial and one of the possible mechanisms for the development of BPH is oxidative stress. Purpose. Study of the effect of phenols with a bulky isobornyl substituent (2,6-diisobornyl-4-methylphenol and 4-hydroxymethyl-2,6-diisobornylphenol)on the growth of experimental BPH and the antioxidant balance of prostate cells in comparison with Prostamol Uno. Materials and мethods. Experiments were carried out on 50 male Wistar rats. BPH was caused by daily administration of sulpiride (60 days) to male rats of late reproductive age. After 2 months, the animals were weighed and sacrificed in a CO2 chamber. The mass, mass coefficient, volume of the lateral lobe of the pancreas were determined, morphological analysis was performed. Investigated prooxidant and antioxidant activity. The results were processed by the method of variation statistics using the Mann-Whitney nonparametric U test. Results. The efficacy of the investigated drugs in BPH decreased in the following sequence: sulpiride + substance 4-hydroxymethyl-2,6-diisobornylphenol (HDB) → sulpiride + substance Dibornol (DB) → sulpiride + Prostamol Uno (PU). When comparing the results of evaluating the anti-prooxidant status with the therapeutic effect of the studied drugs, it was found that isobornylphenols, which are highly effective as prostatotropic drugs, did not show a more significant effect, compared to PU, on the redox potential of prostatic tissue cells. Conclusions. Drugs DB, HDB, PU have a normalizing effect on the level of severity of redox reactions in the sulpiride model of BPH.

Thepara-hydroxymethyl derivatives of 2,6-di-tert-butylphenol, 2,6-diisobornylphenol, 2-isobornyl-6-tert-butylphenol, 2-isobornyl-6-methylphenol, and 2-isobornylphenol were synthesized. A comparative evaluation of the antioxidant properties of the synthesized compounds was carried out inin vitromodels. The activity of derivatives is predetermined by the number and bulkiness of the substituents at theorthopositions relative to the phenolic OH group and is consistent with the relationships previously identified by us for other phenolic antioxidants.

Introduction. The potential of a new compound in the ongoing drugs discovery process is initially explored using virtual instruments, where its activity is predicted based on its molecular structure.Aim. This study aimed to evaluate the pharmacokinetic parameters and possible toxicity of isobornyl compounds based on virtual tools.Material and Methods. Several free Internet resources were used to assess the absorption, distribution, metabolism, excretion (ADME), and toxicity (T) of 2,6-diisobornyl-4-methylphenol (1, Dibornol), 2-hydroxy-3-isobornyl-5-methylbenzaldehyde (2), and 2-((di-n-butylamino) methyl)-6-isobornyl-4-methylphenol (3). Pharmacokinetic properties were calculated on ADMETlab platform. Toxicity and physical properties were evaluated using TEST software based on the structure-property quantification models of organic substances according to structure–property principle. Web server ProTox_II was used for acute toxicity assessment.Results. Plasma protein binding degrees were 76,9% for (1), 85,9% for (2), and 91,8% for (3). All three compounds were capable of penetrating the blood-brain barrier. Dibornol was identified neither as a substrate nor as an inhibitor of P-glycoprotein unlike (2) and (3). The half-life of all compounds was short (about 2 hours); the clearance was slow (about 2 mL/min*kg). The study showed that (2) and (3) potentially exert the toxic effects during the developmental stage of the organism, while ADMETlab showed potential cardio- and hepatotoxicity for (2) and (3), respectively. All compounds had extremely low solubility in water, which affected the assessments of other indicators by TEST software. The ProTox_II server showed the extremely low toxicity LD50 for all compounds (toxicity class 5).

A series of 2-isobornylphenol derivatives containing aminomethyl groups either at ortho-(monoderivatives) or ortho- and para-positions (bis-derivatives) relative to the hydroxy group of phenol moiety was synthesized. Antioxidant properties of the obtained compounds were comparatively evaluated using in vitro models. It was demonstrated that Mannich bases containing an n-octylaminomethyl group are significantly exceeding both starting 2-isobornylphenol and the standard antioxidant, 2,6-di-tert-butyl-4-methylphenol, by their ability to inhibit H2O2-induced erythrocyte hemolysis.

The para-hydroxymethyl derivatives of 2,6-di-tert-butylphenol, 2,6-diisobornylphenol, 2-isobornyl-6-tert-butylphenol, 2-isobornyl-6-methylphenol, and 2-isobornylphenol were synthesized. A comparative evaluation of the antioxidant properties of the synthesized compounds was carried out in in vitro models. The activity of derivatives is predetermined by the number and bulkiness of the substituents at the ortho positions relative to the phenolic OH group and is consistent with the relationships previously identified by us for other phenolic antioxidants.

New hydroxycinnamic acid derivatives were synthesized by reacting malonic acid and 4-hydroxybenzaldehydes with isobornyl and/or alkyl substituents. The antiradical, antioxidant, and membrane-protective activities were assessed in various in vitro models. The bulk of the substituent(s) in the o-position(s) relative to the phenol hydroxyl had a substantial effect on the antioxidant properties of the tested acids.