HK1193105B - Family of polyamine arylethylamide compounds, and their cosmetic or dermocosmetic applications - Google Patents

Abstract

The invention relates to a polyamine aryl ethyl amide compound family, and cosmetic applications or skin cosmetic applications thereof. Specifically, the invention relates to a steady polyamine aryl ethyl amide compound family and applications of the compounds used as inhibitors. The inhibitors inhibit DNA damage induced by skin tissue not enzymatic glycosylated by-products. The invention also relates to cosmetics or cosmetic composition. The composition is aimed at confronting skin diseases pertinent to the glycosylated by-products.

Description

Polyamine aryl ethyl amide compound family and cosmetic or dermocosmetic use thereof

Technical Field

The present invention relates to a family of stable polyamine aryl ethyl amide (polyamine) compounds, and the use of these compounds as inhibitors of DNA damage induced by the by-products of non-enzymatic glycosylation of skin tissue.

The invention also relates to cosmetic or dermocosmetic compositions intended to combat the cutaneous diseases (cutinous disorders) associated with these said glycosylation by-products.

Background

The process of non-enzymatic glycosylation of proteins is a well-established phenomenon, initially consisting of spontaneous condensation between reducing sugars (such as glucose or fructose) and the N-terminal amino functions of some protein or lipoprotein components (such as lysine and arginine). In contrast to the enzymatic glycosylation process encoded by genes, this process disadvantageously results in irreversible changes to the protein after a series of chain reactions and complex molecular rearrangements.

The interference of these changes with changes in biological tissues and their cellular components has clearly been demonstrated to have a variety of physiological consequences: altered function of proteins (disturbed enzyme activity) leading to dysfunction of cellular metabolism, altered mechanical properties of some supporting tissues, impaired activation of inflammatory processes or activation/repair processes of oxidative stress that produce cytokines or reactive oxygen species (oxygen reactive species), and the like. This suggests that such protein alterations play an important role in the development or acceleration of certain diseases, in particular age-related diseases such as diabetes, atherosclerosis, alzheimer's and parkinson's disease, renal failure, etc. (j.uribarri et al, j.gerntol.in biol.sci.med.sci. (2007), vol.62, p.437-433).

The influence of the non-enzymatic glycosylation process of proteins, in particular the influence on aging, is undisputable, at least for skin. In fact, once glycation occurs by spontaneous condensation of sugars, skin proteins (in particular structural proteins like collagen or elastin) become stiff as covalent crosslinks between fibres accumulate. The skin viscoelasticity is therefore reduced and the signs of new or existing wrinkles are increased. Turnover of these skin proteins is also slowed (Dyer D.G et al, j. wink. invest. (1993), vol 91, p. 2463-9).

Another well-known knowledge of the non-enzymatic glycosylation process of proteins today, which is not trivial, is that some substances, often called 'glycosylation by-products', are also released in this complex process, which behave like true toxins. For example, furthermore, as is the case in the recent article "glycoxins: a porous which to health. This involves a variety of substances which are not readily definable, but from which, for example, glyoxal (glyoxal), methylglyoxal (methyl-glyoxal) or deoxyglucosone (deoxyglucosone) can be distinguished.

One characteristic of glycotoxins that is particularly harmful to organisms is their ability to damage cellular DNA. In fact, these changes may induce mutations in genes that cause genomic instability. For example, mutagenicity of by-products formed when Bovine Serum Albumin (BSA) is incubated with glucose in vitro is reported (Ogata M. et al, J.Wink.biochem.Nutr. (2006), Vol.38, p.176-. Several alpha-ketoaldehydes (alpha-ketoaldehydes), especially glyoxal and methylglyoxal as described above, are capable of inducing genetic mutations in bacterial strains and human cells (Ueno h. et al, transferred. res. (1991), Vol. 251, p. 99-107). It has recently been reported that the potential genotoxicity of glycotoxins is likely to be caused by stable adducts formed by reaction with some DNA building nucleosides (Ahmad s., biochem. biophysis. res. common. (2011), volume 15, pages 568-74). Methylglyoxal thus specifically targets guanine nucleosides (guanosines) from the nucleotide chain of DNA, leading to the occurrence of mutations during DNA replication, especially in the absence of effective repair (Wuenschell g.e. et al, Biochemistry (2010), vol. 49, p. 1814-1821).

Thus, with these different statements, the applicant, according to the cosmetic or dermocosmetic aim, has identified substances capable of interfering with the non-enzymatic glycosylation process of proteins with the main aim of avoiding any damage caused by the production of glycotoxins, which affects the DNA of the skin cells. This is indeed critical in today's cosmetics industry, especially for preventing premature senescence of skin cells, protecting the genomic DNA of cells such as keratinocytes or fibroblasts.

In accordance with this aim, the applicant has more closely sought an original structure (original structure) capable of trapping the glycosylation by-products in the course of the non-enzymatic glycosylation of proteins, such as the genotoxic glycotoxins described above, while ensuring that the resulting adducts (glycotoxins-traps) are not only genotoxic but also prevent these adducts from causing the formation of products which are themselves genotoxic. In the framework of cosmetic or dermocosmetic use, it is first of all important to ensure, in addition to the harmlessness of the substances, the harmlessness of the reaction by-products resulting from the targeted cosmetic activity.

With regard to the prior art relating to the Applicant's goals, to the Applicant's knowledge, the prior art essentially discloses substances or preparations which show a simple capacity to prevent or inhibit the formation of glycosylation products. Thus, for example, guanidine (guanidine) family substances, such as aminoguanidine (aminoguanidine) and metformin (metform), are of therapeutic benefit due to their ability to bind early glycosylation byproducts (Matsuki k, et al, Atherosclerosis (2009), vol 206, p 434-8). Several thiazole salts (salts of thiazolium), especially N-benzoyl thiazothiazole bromide (N-phenyl thiazoium bromide) or "PTB", are also of therapeutic benefit due to their ability to disrupt cross-links between proteins (Ulrich P. et al, Diabetologia (1997), Vol.40, p.s 157-S159).

In the field of skin care, some of the benzofuranhydroxylated derivatives, with limited characteristics for the non-enzymatic glycosylation of the skin or keratin, even declared inhibitory, are used for cosmetic purposes (patent FR 2833165). The applicant of patents FR2802425 and WO2010/010248 succeeded in identifying plant extracts (Ericaceae family and gymnorrhizaceae family (Sapotaceae) respectively) with the same limiting or inhibiting effect on skin cell and protein protection. It must be emphasized that none of these documents provide a combination of the following information: information on the benefit to skin cell DNA when specifically subjected to genotoxic glycotoxins, and information on glycosylation byproducts that become detoxified. In a broader sense, the antioxidant properties of products with imidazole groups (imidazole groups) for various therapeutic or cosmetic applications are also cited in the applicant's patent application WO 95/12581.

Disclosure of Invention

The linear polyamine structures such as the spermine (speramine) and spermidine (speramine) targets for the non-enzymatic glycosylation of certain proteins were the first basis (Gugliucci A. et al Life Sciences (2003), volume 72, p. 2603-2616), whereby the applicant discovered a simplified family of compounds, obtained by coupling reactions between amino alkanoic acids (aminoalkanoic acids) and primary ethylamines (primary ethylamines) carrying aromatic or heteroaromatic rings, showing the general behavior of inhibitors to inhibit DNA induced by deleterious glycosylation byproducts such as glycotoxins. The compounds of the present invention, represented by the following general formulae (I), (II) and (III), exhibit the following advantageous properties:

the ability to protect the target nucleoprotein in favor of the glycotoxin, histone [ see test 1 below ]. Histones constitute essential proteins with DNA surrounding nucleosomes, as they coordinate the level of tightening or relaxation of chromatin (the form in which DNA is present in the nucleus) which allows the repair system to access sites of DNA damage (Roberts et al, propels.res. (2003), 522, pages 45-56);

the ability of the proteins capable of clearing fructose to mutagenize the genotoxic by-products produced by non-enzymatic glycosylation, reflected in the ability to significantly reduce or even completely eliminate the number of mutations induced in the reference prokaryotes (called "back mutations") [ see test 2 below ];

ability to clear the mutagenicity of the reference glycotoxin (methylglyoxal) [ see test 3 below ];

-the ability to interfere with the progress of non-enzymatic glycosylation with the following properties: under glycosylation conditions, no genotoxic byproducts were produced, or the evolution toward the formation of these byproducts under these conditions [ see test 4 below ].

The first object of the present invention is therefore a family of polyamine arylacetamide compounds, characterized in that it is represented by the following general formula (I):

wherein: n =1 ~ 4, and

except for compounds of n =3 and R = imidazole

According to a preferred embodiment of the present invention, the compound of the present invention is represented by the following general formula (II):

wherein: n =1 ~ 2, and

according to another preferred embodiment of the present invention, the compound of the present invention is represented by the following general formula (III):

wherein: n =1 ~ 2, and

as non-exhaustive examples of polyamine arylethylamide compounds having general formula (I), mention may be made of the following compounds:

n- ((4-Imidazolyl) ethyl) -L-lysinamide (N- ((4-imidazoyl) ethyl) -L-lysine)

N- ((4-imidazolyl) ethyl) -alpha, gamma-diaminobutanamide (N- ((4-imidazolyl) ethyl) -alpha, gamma-diamino-butanamide)

N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide (N- ((4-imidazolyl) ethyl) - α, β -diaminopropanamide)

N- ((3-indolyl) ethyl) -alpha, beta-diaminopropionamide (N- ((3-indolyl) ethyl) -alpha, beta-diaminopropanamide)

N- ((4-hydroxyphenyl) ethyl) -alpha, beta-diaminopropionamide (N- ((4-hydroxyphenylyl) ethyl) -alpha, beta-diaminopropanamide)

N- ((3,4-dihydroxyphenyl) ethyl) -alpha, beta-diaminopropionamide (N- ((3,4-dihydroxyphenyl) ethyl) -alpha, beta-diaminopropanamide)

As non-exhaustive examples of polyamine arylethylamide compounds having general formula (II), mention may be made of the following compounds:

n- ((4-imidazolyl) ethyl) -alpha, gamma-diaminobutanamide

N- ((4-imidazolyl) ethyl) -alpha, beta-diaminopropionamide

N- ((3-indolyl) ethyl) -alpha, beta-diaminopropionamide

N- ((4-hydroxyphenyl) ethyl) -alpha, beta-diaminopropionamide

N- ((3,4-dihydroxyphenyl) ethyl) -alpha, beta-diaminopropionamide

The polyamine aryl ethylamide compound having the general formula (III) is as follows:

n- ((4-imidazolyl) ethyl) -alpha, gamma-diaminobutanamide

N- ((4-imidazolyl) ethyl) -alpha, beta-diaminopropionamide

According to a further advantageous embodiment of the invention, N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide and N- ((4-imidazolyl) ethyl) - α, γ -diaminobutyramide are used in particular as polyamine arylethylamide compounds in the above-mentioned formulae (I), (II) and (III).

The compounds of the invention can be synthesized in base form or salt form according to methods known to those skilled in the art, for example, according to typical chemical routes of protection, coupling, deprotection.

According to a second aspect, the invention also comprises a composition for cosmetic or dermocosmetic use intended to prevent or limit the "genotoxic risk" associated with non-enzymatic glycosylation processes, in particular the formation of genotoxic glycosylation by-products.

The composition comprises, as the main active ingredient, a compound of general formulae (I), (II) and (III), for example as defined above, and any physiologically acceptable additives. It is in the form of a powdery solid, soluble in aqueous or hydroalcoholic media, but insoluble in ethanol, stable over a wide range of pH values (3-9).

In the course of the present invention, "primary active ingredient" is understood to be an active substance capable of detoxifying the sugar toxin and combating its formation and harmful effects.

Advantageously, the amount of compound of formula (I) in the composition herein is from 0.01% to 1% by weight, preferably from 0.01% to 0.5% by weight, particularly preferably from 0.01% to 0.1% by weight, and very particularly preferably from 0.02% to 0.2% by weight, relative to the total weight of the composition.

The compositions according to the invention are suitable for topical application to the skin and may take all forms normally used for such application. As illustrative but not limiting examples, the compositions are in the form: emulsions, lotions, creams, aqueous or hydroalcoholic gels, powders, and a variety of emulsions that may be micro-or nano-emulsions, and the like.

The compositions according to the invention may also be formulated for oral route administration, by way of example and without limitation, tablets, capsules, pills, sachets (pouch), pastes, liquids (emulsified or non-emulsified).

The composition according to the invention may comprise, as physiologically acceptable additives, at least one additive known to the person skilled in the art and compatible with the cosmetic and dermocosmetic field, chosen from: oils, waxes, silicone elastomers, surfactants, co-surfactants, thickeners and/or gelling agents, humectants, emollients, organic or inorganic fillers, light stabilizers, preservatives other than aldehyde donor preservatives, dyes, humectants, tightening agents (tensors), chelating agents, fragrances, and the like, and mixtures thereof.

The compositions according to the invention may also comprise one or more additional active ingredients, but the skilled person will ensure that possible active supplements and their proportions are selected in such a way as not to affect the recognised beneficial properties of the compounds of the invention. These additional active ingredients may be selected from the following list (but this list is not limiting): a desugaring agent; agents that increase collagen or elastin synthesis or prevent their degradation; agents that increase synthesis of mucopolysaccharides or proteoglycans or prevent their degradation; an agent that increases cell proliferation; depigmenting or pigmentation promoting agents (pro-colouring agents); an antioxidant or anti-radical agent or anti-fouling agent; a humectant; an agent that stimulates lipolysis; a drainage agent (i.e., antidote) or antidote; an anti-inflammatory agent; a penetration enhancer; a stripping agent (desquamative agent); soothing and/or anti-irritants; an astringent; agents acting on the microcirculation, etc.; and mixtures thereof.

The composition according to the invention is intended to prevent or fight any skin disease associated with the non-enzymatic glycosylation process of proteins and the formation of genotoxic glycotoxins, selected from the group consisting of skin cell premature aging, skin lightening (skin lightening), etc. Of these compounds, the polyamine arylethylamide compound preferably has the formula (III), in particular an N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide compound.

Another object of the present invention relates to the cosmetic and dermocosmetic use of a polyamine aryl ethyl amide compound as an inhibitor of DNA damage induced by genotoxic saccharide toxins, said polyamine aryl ethyl amide compound having the following general formula (I):

wherein: n =1 ~ 4, and

preferably, in the above application, the compound of formula (III) is selected:

wherein: n =1 ~ 2, and

and is preferably an N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide compound.

Another object of the present invention relates to a cosmetic care method comprising the application of a cosmetic composition as defined previously to at least a skin portion of the body, according to an effective amount against a skin disorder associated with non-enzymatic glycosylation by-products of the skin tissue.

Detailed Description

Example 1:

for purposes of illustration, two formulation examples of the compositions of the present invention having a polyamine aryl ethyl amide compound of the general formula (I) above are mentioned below:

formulation A (cream)

Formulation B (gel)

Example 2:

the invention is illustrated below by the following tests (tests 1 to 4) mentioned earlier in the description of the invention, which are for reference only.

It is also noteworthy that the initial results of in vivo studies (repeated patch test, service provider: EvicRomania Company) conducted on humans show good skin tolerance of the polyamine aryl ethyl amide compounds according to the present invention.

Test 1: evidence for the ability of the polyamine aryl ethyl amide compounds of general formula (I) to protect some of the proteins necessary for nuclear DNA frizzing, histones, against the reference glycotoxin (methylglyoxal)

The purified histone solution enriched in H1 histone (5mg/ml) was incubated at 37 degrees with stirring for 24 hours in the presence of the reference saccharide toxin MGO (10 mM). To follow the specific fluorescence of the product from the non-enzymatic glycosylation of histones, the MGO fluorescence, as well as the fluorescence of the product from the glycotoxin trap, needs to be removed. For this purpose, the reaction mixture is dialyzed. It was then introduced into a dialysis cassette (dialysis tape) and subjected to 3 successive baths of 3 hours each, each bath being NaH with MGO diluted therein₂PO₄Buffer (83.3 mM). The fluorescence of the dialyzed mixture was measured using a fluorimeter (lambda excitation: 340nm; lambda emission: 470nm), which indicates the damage of histones caused by the reaction with MGO (adduct formation). The units of measurement correspond to RFU ("Relative Fluorescence Unit").

TABLE 1

The results show that the N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide and N- ((4-imidazolyl) ethyl) - α, γ -diaminobutyramide compounds according to the invention have a strongly reduced ability to form non-enzymatic glycosylation products as a result of the reaction between the saccharide toxin and the histone.

Test 2: evidence for the ability of polyamine aryl ethyl amide compounds of formula (I) to detoxify saccharide toxins released from glycosylated proteins

This study was performed on a Salmonella typhimurium (TA 100) bacterial strain belonging to a reference strain for the Ames regulatory test (ICH guide Committee, guidelines for specific aspects of regulatory genotoxicity testing of drugs on 7/19. 1995) (guidelines for pharmaceuticals). The aim was to determine the number of revertant colonies (reverttantrolones) representing mutagenicity of the casein-fructose system among the colonies of the mutant strains in the presence or absence of the compounds of the invention.

In the experiment, 2.7g of D- (+) -fructose (D- (+) -fructose) was dissolved in 100ml of phosphate buffer at room temperature. After 20g of a colorless transparent solution (C) was collected_Fructose=150mM), 0.600g of sodium caseinate is added until complete dissolution. This solution was then added to a 2x10mL screw capped test tube and then placed in a 120 ℃ oil bath for 1 hour.

In parallel, the TA100 strain was grown in Nutrient Broth Oxoid N.degree.2 (NBO2) supplemented with ampicillin. The medium was placed on an orbital shaker (88rpm) at 37 ℃ overnight to place the bacteria in the exponential growth phase (10)⁷～10⁹Bacteria/ml) furthermore, 0.92g of the compound according to the invention N- ((4-imidazolyl) ethyl) - α -diaminopropionamide was dissolved in freshly prepared Phosphate Buffered Saline (PBS) to different concentrations (400. mu.l) of the compound according to the invention 500. mu.l of glycated casein and 100. mu.l of the above-mentioned bacterial suspension were added in succession, the resulting mixture was at 37 ℃Incubate for 30 minutes with orbital stirring (122 rpm). 2ml of soft agar maintained at 45 ℃ and supplemented with biotin histidine (biotin) was added. After mixing using Vortex, they were deposited in Petri dishes (Petridih) containing Vogel-Bonner hard agar. After coagulation, the dishes were transferred to a 37 ℃ incubator over the course of 48-72 hours.

The experiments were carried out according to the TA100 strain preincubation method without metabolic activators. Colony counting was then performed manually.

The results are presented in table 2 below, in comparison to a negative control (PBS phosphate buffer).

TABLE 2

Compound (I)	Number of revertant colonies	R
			Control (PBS)	84	1
Fructosylated casein	138	1.64
			N- ((4-Imidazoyl) ethyl) - α -diaminopropionamide (7.5mM)	119	1.42
N- ((4-Imidazoyl) ethyl) - α -diaminopropionamide (15 mM))	93	1.11

The results show that the N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide compounds according to the invention are capable of strongly reducing the toxicity of the resulting glycotoxin. A dose-effect relationship was also observed.

And (3) testing:evidence demonstrating the ability of polyamine aryl ethyl amide compounds of formula (I) to detoxify a reference saccharide toxin (methylglyoxal (MGO))

The study was performed in almost the same manner as in test 2 above, but using MGO at a concentration of 140. mu.M instead of 500. mu.l of glycated casein. In addition to the N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide compounds, the following compounds of the invention were tested at different concentrations:

n- ((4-hydroxyphenyl) ethyl) -alpha, beta-diaminopropionamide

N- ((4-imidazolyl) ethyl) -alpha, gamma-diaminobutanamide

N- ((3,4-dihydroxyphenyl) ethyl) -alpha, beta-diaminopropionamide

N- ((4-imidazolyl) ethyl) -L-lysyl amine

The results are summarized in table 3 below, in comparison to PBS phosphate buffer (negative control).

TABLE 3

The results show that a relatively wide range of compounds of the invention are capable of strongly reducing the mutagenicity of methylglyoxal.

Test 4: evidence of the ability of the polyamine aryl ethyl amide compound of formula (I) to interfere with the non-enzymatic glycosylation process and not form mutagenic by-products.

This study was performed in almost the same manner as test 2 above, except that D- (+) -fructose was replaced with D-glucose under the following conditions. In the experiment, 18.02g of D-glucose was dissolved in 100mL of water at room temperature. After adjusting the pH with sodium hydroxide, a solution corresponding to 10mM of the compound of the invention, N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide compound, in 10ml was sampled and introduced. The resulting reaction mixture was then poured into a test tube with a screw cap and heated at 100 ℃ for 80 minutes.

In parallel, the TA100 strain was grown in Nutrient Broth Oxoid N.degree.2 (NBO2) supplemented with ampicillin. The medium was placed on an orbital shaker (88rpm) at 37 ℃ overnight to place the bacteria in the exponential growth phase (10)⁷～10⁹Bacteria/ml).

Mu.l of the test solution was added to 100. mu.l of the above bacterial suspension and 500. mu.l of PBS phosphate buffer, and the resulting mixture was incubated for 1 hour at 37 ℃ with orbital stirring (122 rpm). 2ml of soft agar maintained at 45 ℃ and supplemented with biotin histidine (biotin) was added. After mixing using Vortex, it was deposited in Petri dishes containing Vogel-Bonner hard agar. After coagulation, the dishes were transferred to a 37 ℃ incubator over the course of 48-72 hours.

The experiments were carried out according to the TA100 strain preincubation method without metabolic activators. Colony counting was then performed manually. The results are presented in table 2 below, following a negative control (PBS phosphate buffer) and a positive control (NaN 3 sodium azide) control.

TABLE 4

Compound (I)	Number of revertant colonies
		Control (PBS) (spontaneous reversion)	88
Control (NaN)3) (Positive control)	211
		N- ((4-Imidazoyl) ethyl) - α -diaminopropionamide (1.667. mu.l/dish)	104
N- ((4-Imidazoyl) ethyl) - α -diaminopropionamide (25. mu.l/dish)	95
		N- ((4-Imidazoyl) ethyl) - α -diaminopropionamide (50. mu.l/dish)	90
N- ((4-hydroxyphenyl) ethyl) - α -diaminopropionamide (50. mu.l/dish)	93
		N- ((4-Imidazoyl) ethyl) - α, gamma-diaminobutanamide (50. mu.l/dish)	93
N- ((4-Imidazoyl) ethyl) -L-lysyl amine) (50. mu.l/dish)	99

The results show that the polyamine arylethylamide compounds of general formula (I) according to the invention, although under glycosylation conditions, do not produce mutagenic by-products.

Claims (16)

1. A polyamine aryl ethyl amide compound characterized in that the polyamine aryl ethyl amide compound is represented by the following general formula (II):

wherein: n is 1 to 2, and

2. the polyamine arylethylamide compound of claim 1 wherein the polyamine arylethylamide compound is N- ((4-imidazolyl) ethyl) - α, γ -diaminobutyramide or N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide.

3. The polyamine arylethyl amide compound of claim 2 wherein the polyamine arylethyl amide compound is N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide.

4. Cosmetic or dermocosmetic composition, characterized in that it comprises, as main active ingredient, a compound as defined in any one of claims 1 to 3, and any physiologically acceptable dermatological additive.

5. The composition according to claim 4, wherein the compound of formula (II) is selected from the group consisting of N- ((4-imidazolyl) ethyl) - α, γ -diaminobutanamide and N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide.

6. The composition of claim 5, wherein the compound of formula (II) is N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide.

7. The composition according to any one of claims 4 to 6, wherein the compound of formula (II) is contained in an amount of 0.01 to 1% by weight relative to the total weight of the composition.

8. The composition according to any one of claims 4 to 6, further comprising one or more additional active ingredients selected from the group consisting of: a desugaring agent; agents that increase collagen or elastin synthesis or prevent their degradation; agents that increase synthesis of mucopolysaccharides or proteoglycans or prevent their degradation; an agent that increases cell proliferation; a decolorizing agent or coloring promoter; an antioxidant or anti-radical agent or anti-fouling agent; a humectant; an agent that stimulates lipolysis; a drainage agent or antidote; an anti-inflammatory agent; a penetration enhancer; a release agent; soothing and/or anti-irritants; an astringent; agents acting on the microcirculation; and mixtures thereof.

9. Use of a compound of general formula (II) below as main active ingredient for the preparation of a cosmetic or dermocosmetic composition for preventing or limiting skin diseases associated with the formation of non-enzymatic glycosylation by-products and genotoxic glycotoxins:

wherein: n is 1 to 2, and

10. use according to claim 9, for preventing or limiting premature aging of skin cells or skin lightening.

11. Use according to claim 9 or claim 10, wherein the compound of formula (II) is N- ((4-imidazolyl) ethyl) - α, γ -diaminobutanamide or N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide.

12. Use according to claim 11, wherein the compound of formula (II) is N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide.

13. Use of a compound of the following general formula (II) as a main active ingredient in the preparation of a cosmetic or dermocosmetic composition as an inhibitor for inhibiting DNA damage induced by a genotoxic glycotoxin:

wherein: n is 1 to 2, and

14. use of a compound of general formula (II) below as main active ingredient for the preparation of a cosmetic or dermocosmetic composition for use as an agent capable of combating the mutagenic effects of glycotoxins:

wherein: n is 1 to 2, and

15. use according to claim 13 or 14, wherein the compound of general formula (II) is N- ((4-imidazolyl) ethyl) - α, γ -diaminobutanamide or N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide.

16. Use according to claim 15, wherein the compound of formula (II) is N- ((4-imidazolyl) ethyl) - α, β -diaminopropionamide.