New compounds derived from morin, method for obtaining them and their uses

Abstract

The present invention relates to new compounds derived from morin, to the synthesis and use of the new compounds, with antioxidant and anti-inflammatory activity against ultraviolet (UV) radiation.

Description

[0001] NEW COMPOUNDS DERIVED FROM MORINA, PROCEDURE FOR OBTAINING THEM AND USES GIVEN TO THEM

[0002] DESCRIPTION

[0003] The present invention relates to new compounds derived from morin, to the synthesis and use of the new compounds, with antioxidant and anti-inflammatory activity against ultraviolet (UV) radiation.

[0004] Background of the invention

[0005] The skin acts as the first line of defense against various external agents, including ultraviolet (UV) radiation, which generates oxidative damage to the skin, accompanied by an inflammatory response and skin barrier dysfunction. Exposure to UV radiation is known to be the main risk factor for the development of skin cancer, which accounts for one in three cases of cancer worldwide, according to the WHO. Despite being one of the most easily preventable types of cancer, the number of cases is increasing. Furthermore, UVB radiation is closely linked to skin aging, which is clinically characterized by dryness, pigmentation, laxity, wrinkles, and erythema. Tissue damage is reflected in functional and structural alterations, with an inflammatory basis, affecting components of the extracellular matrix and triggering the activation of proteolytic enzymes, such as metalloproteinases.For this reason, the use of sunscreens that protect the skin from the harmful effects of solar radiation is essential. Currently, the cosmetics industry is advancing in the development of new filters, and social awareness campaigns to prevent sun damage are increasing. However, factors such as incorrect and insufficient application of sunscreens, lack of reapplication, or the lack of photostability of the filters fail to ensure complete sun protection, especially in patients with pre-existing dermatological conditions or who are highly sensitive to solar radiation. For this reason, the search for new compounds with antioxidant and anti-inflammatory activity that can be incorporated as adjuvants in sunscreens and contribute to optimal photoprotection is of great interest.The study of natural ingredients is at the forefront of research into new bioactive compounds. Many of these ingredients have been used as biological filters, which are considered substances with antioxidant activity that decrease the production of free radicals, reducing cellular damage and therefore helping to prevent photoaging and skin cancer. Some examples of these products that have demonstrated photoprotective activity include an extract of the fern Polypodium leucotomos, an extract of the grass Deschampsia antarctica, certain mycospohna-type amino acids isolated from algae, carotenoids such as p-carotene, and a multitude of phenolic compounds isolated from plants such as Vitis vinifera L., Ruta graveolens L., and Ginkgo biloba L., among others.

[0006] Of the wide variety of bioactive natural ingredients, phenolic compounds and carotenoids represent two of the most studied groups, with a wide variety of properties, including antioxidant, anti-inflammatory and antitumor effects, which make them potentially useful as photoprotective agents. Regarding phenolic compounds, those that present the greatest potential to protect the human body against reactive oxygen species (ROS) are a subclass of flavonoids known as flavonols, among which morin, also known as mohn, 2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one, or 2',3,4',5,7-pentahydroxyflavone stand out.

[0007] Morin is a polyphenol originally isolated from members of the Moraceae family, although it is also found in species of the Rosaceae, Fagaceae, and Myrtaceae families. This flavonoid has been shown to be an oral chemopreventive agent against carcinogenesis both in vitro and in vivo. Morin has also been evaluated as a component of sunscreens, following its encapsulation in polymeric nanoparticles.

[0008] Regarding these applications, morin has been described as part of the composition of nutraceuticals aimed at the prevention / treatment of cancer in patent application US20100209388A1. Additionally, morin has been included in the preparation of mixtures of active ingredients free of metal salts, useful for the treatment of cancer, non-malignant tumors, as well as antibacterial, antifungal, and antiviral agents, as described in application W01988003805A1.

[0009] Like other naturally occurring polyphenols, morin is a compound that can undergo structural modifications to enhance its stability and optimize its applicability. One way to improve the chemical stability and pharmacological potential of these chemicals with pharmacological potential is through chemical derivatization.

[0010] Based on this background, there is a great need to find new ingredients that provide improved antioxidant and anti-inflammatory biological activity compared to already known compounds.

[0011] Description of the invention

[0012] In the present invention, the carbonyl group of morin, also known as morin or 2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one, is used to prepare Schiff bases, which are known as azomethines or amines. Structurally, a Schiff base is a nitrogen analogue derived from an aldehyde or ketone in which its carbonyl bond (C=O) is replaced by a double bond (C=N). Therefore, the distinctive functional group of this class of derivatives is represented by the general formula R a R b C=NR c The most common method for preparing Schiff bases involves condensation reactions between the carbonyl of aldehydes or ketones with compounds that have a -NH2 group, such as primary amines (RNH2), hydroxylamines (NH2OH), hydrazines (NH2NH2) and semicarbazides (NH2NHCONH2), in which a water molecule is eliminated.

[0013] A first aspect of the invention are compounds derived from morin of formula (I) where the group (C=O) is replaced by a double bond (C=NR).

[0014] Therefore, the first aspect of the invention relates to a compound of formula (I),

[0015] Formula (I) where R is selected from: a saturated, linear or branched Ci-Ce alkyl radical, a linear or branched C2-C6 alkenyl radical; a linear or branched C2-C6 alkynyl radical, a C3-C12 cycloalkyl radical, a C3-C12 aryl radical, a -XR radical 1 , a radical -NHC=XNR 2 R 3 , a radical -NHR 4 , a radical -NHCOOR 5 , a radical -NHCOR 6 ; where X is selected from O, S; where R 1 , R 2 R 3 , R 4 , R 5 , and R 6They may be the same or different and are selected from H, a saturated linear or branched Ci-Ce alkyl radical, a linear or branched Ci-Ce alkenyl radical; a linear or branched Ci-Ce alkynyl radical, a C3-C12 cycloalkyl radical, a C3-C12 aryl radical.

[0016] The process for obtaining the products of formula (I) of the invention is a simple process, with a single reaction step, and with simple reaction conditions that can be carried out in any chemical synthesis laboratory.

[0017] The present invention contemplates the preparation of compounds of general formula (I) using morin (2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one), compound of formula (II) and nitrogen reagents for the formation of azomethine derivatives or Schiff bases in the synthesis steps, in suitable proportions and reaction medium.

[0018] Therefore, a second aspect of the invention relates to a process for obtaining compounds of general formula (I) as defined above.

[0019] Formula (I) comprising the steps of: reacting 2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one of formula

[0020] (II)

[0021] Formula (II) with a nitrogen compound of formula H2NR, in the presence of an organic solvent; where R is selected from: a saturated, linear or branched C2-C6 alkyl radical, a linear or branched C2-C6 alkenyl radical; a linear or branched C1-C1e alkynyl radical, a C3-C12 cycloalkyl radical, a C3-C12 aryl radical, a -XR radical 1 , a radical -NHC=XNR 2 R 3 , a radical -NHR 4 , a radical -NHCOOR 5 , a radical -NHCOR 6 ; where X is selected from O, S; where R 1 , R 2 R 3 , R 4, R 5 , and R 6 They may be the same or different and are selected from H, a saturated linear or branched Ci-Ce alkyl radical, a linear or branched Ci-Ce alkenyl radical; a linear or branched Ci-Ce alkynyl radical, a C3-C12 cycloalkyl radical, a C3-C12 aryl radical.

[0022] These modifications of morin improve the absorption capacity in the UV-visible (vis) range and the stability of these molecules of formula (I), while also maintaining their antioxidant and photoprotective activity. Therefore, the compounds of formula (I) of the invention can be used as adjuvants in photoprotection, with the aim of preventing the appearance of cancerous lesions, the exacerbation of photodermatoses, and also reducing premature skin aging caused by exposure to solar radiation.

[0023] The present invention relates to new compounds derived from morin, to the synthesis and use of new compounds, Schiff bases, with antioxidant and anti-inflammatory activity against UV radiation. Therefore, the applicability of the present invention could be encompassed within the cosmetic and / or dermatological field and, specifically, as part of photoprotective formulations as an adjuvant for the prevention of skin cancer and cellular damage or premature photoaging thereof. The compounds of formula (I) can be adjuvants of the photoprotective activity of physical and chemical filters. Then, one aspect of the invention relates to the compounds of formula (I) according to the invention for their use as adjuvants of photoprotectors.

[0024] These modifications of morin provide greater UV-vis light absorption capacity, improving and / or preserving the photoprotective activity of morin itself.

[0025] Therefore, other aspects of the invention are: the use of the product of the invention defined above in the preparation of a cosmetic or dermatological composition to protect a mammal from UV-vis radiation; likewise, an aspect of the invention is a compound of formula (I) for use in the protection of a mammal from UV-vis radiation and finally another aspect of the invention is a compound of formula (I) for use in the prevention of skin cancer and for use in preventing skin aging.

[0026] Another aspect of the invention is the cosmetic composition or the dermatological composition comprising the product of formula (I) of the invention.

[0027] Brief description of the drawings

[0028] Figure 1 shows a comparison of the UV-vis absorption spectra in the 200-500 nm range of morin (solid line), morin oxime (dot-dash line), and morin semicarbazone (dashed line). The figure illustrates the UV absorption capacity by plotting the molar extinction coefficient (£) and wavelength for each of the compounds synthesized in Example 1.

[0029] Figures 2A, 2B and 2C show the evaluation of anti-inflammatory activity as IL-6 production (pg / ml) of morin (2A) and the two compounds obtained in Example 1, morin oxime (2B) and morin semicarbazone (2C) in HaCaT keratinocytes exposed to UVB radiation.

[0030] Figures 3A and 3B show the evaluation of the intracellular antioxidant activity (%ROS) of morin (FIG. 3A) and morin semicarbazone (FIG. 3B) obtained in Example 1 in HaCaT keratinocytes exposed to UVB.

[0031] Figures 4A, 4B and 4C show the effect of fucoxanthin (4A) and fucoxanthin combined with morin (4B) or morin semicarbazone (4C) of Example 1 on cell viability (%cell viability) in HaCaT keratinocytes exposed to UVB radiation.

[0032] Figure 5A, 5B and 5C show the evaluation of the intracellular antioxidant activity (%ROS) of fucoxanthin (5A) and fucoxanthin combined with morin (5B) or morin semicarbazone (5C) of Example 1 in HaCaT keratinocytes exposed to UVB radiation.

[0033] Figure 6A, 6B and 6C show the evaluation of the anti-inflammatory activity (IL-6(pg / ml) of fucoxanthin (6A) and fucoxanthin combined with morin (6B) or morin semicarbazone (6C) of Example 1 in HaCaT keratinocytes exposed to UVB radiation.

[0034] Description of a preferred embodiment

[0035] As stated, the first aspect of the invention relates to: A compound of formula (I)

[0036] Formula (I) where R is selected from: a saturated, linear or branched Ci-Ce alkyl radical, a linear or branched C2-C6 alkenyl radical; a linear or branched C2-C6 alkynyl radical, a C3-C6 cycloalkyl radical, a C3-C6 aryl radical, a -XR radical 1 , a radical -NHC=XNR 2 R 3 , a radical -NHR 4 , a radical -NHCOOR 5 , a radical -NHCOR 6 ; where X is selected from O, S; where R 1 , R 2 R 3 , R 4 , R 5 , and R 6 They may be the same or different and are selected from H, a saturated, linear or branched C1-C2 alkyl radical, a linear or branched C2-C6 alkenyl radical; a linear or branched C2-C6 alkynyl radical, a C3-C6 cycloalkyl radical, a C3-C6 aryl radical.

[0037] As stated, the term Ci-Ce alkyl refers to a straight or branched hydrocarbon chain radical consisting of 1 to 6 carbons, containing no unsaturation, and attached to the rest of the molecule by a single bond, e.g., methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, t-butyl, 1-pentyl.

[0038] In the present invention the term "C2-C6 alkenyl" refers to a straight or branched chain of two to six carbon atoms containing one or more double bonds, for example, ethenyl, 2-propenyl, and the like.

[0039] In the present invention the term "C2-C6 alkynyl" refers to a straight or branched chain of two to six carbon atoms containing one or more triple bonds, for example, ethynyl, 2-propynyl, and the like.

[0040] In the present invention, the term "Cs-Ce cycloalkyl" refers to a straight chain of two to six carbon atoms forming a cyclic structure, such as cyclopropyl. In the present invention, the term "Cs-Ce aryl" refers to a cyclic aromatic radical such as phenyl.

[0041] In this specification and claims, the term "alkoxy" is used to designate a group of formula: R 1 O- in which R 1 represents what has been defined above. Preferably, the term "alkoxy" is used to designate an alkoxy with an alkyl group of 1 to 3 carbon atoms, such as methoxy or ethoxy.

[0042] Preferably R is selected from: a saturated, linear or branched C1-C3 alkyl radical, a linear or branched C2-C3 alkenyl radical; a linear or branched C2-C3 alkynyl radical, a radical -XR 1 , a radical -NHC=XNR 2 R 3 ,a radical -NHR 4 , a radical -NHCOOR5 , a radical -NHCOR 6 ; where X is selected from O, S; where R 1 , R 2 R 3 , R 4 , R 5 , and R 6 They may be the same or different and are selected from H, a saturated linear or branched C1-C3 alkyl radical, a linear or branched C2-C3 alkenyl radical; a linear or branched C2-C3 alkynyl radical. More preferably, R is selected from OR 1 and a radical -NHC=XNR 2 R 3 .

[0043] In a preferred embodiment, the product of formula (I) is morin oxime, (2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one oxime). In another preferred embodiment, the product of formula (I) is morin semicarbazone, (2-(2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-ylidene)hydrazine-1-carboxamide).

[0044] A second aspect is the process for obtaining the compounds of formula (I) as defined above. In a preferred embodiment, 2-(2,4-Dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one of formula (II) is reacted with hydroxylamine hydrochloride or semicarbazide hydrochloride.

[0045] Preferably in the process of the invention the organic solvent is selected from: methanol, ethanol, propanol, isopropanol, butanol, iso-, sec- or tert- butanol, pentanol, hexanol, heptanol, octanol or ethylhexanol. More preferably methanol. The preparation of these compounds of general formula (I) using morin and nitrogen-containing reagents for the formation of azomethine derivatives or Schiff bases can be carried out preferably using equimolar proportions, more preferably with an excess of the nitrogen-containing reagent.

[0046] The compound (2-(2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-ylidene)hydrazine-1-carboxamide) has demonstrated antioxidant and anti-inflammatory activities, which are enhanced in the presence of fucoxanthin.

[0047] Therefore, an embodiment of the invention relates to a composition comprising the compound (2-(2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-ylidene)hydrazine-1-carboxamide) and fucoxanthin.

[0048] These modifications of morin improve the absorption capacity in the UV-vis range and the stability of these molecules of formula (I), while also maintaining their antioxidant and photoprotective activity. Therefore, the compounds of formula (I) of the invention can be used as adjuvants in photoprotection, with the aim of preventing the appearance of cancerous lesions, the exacerbation of photodermatoses, and, furthermore, reducing premature skin aging caused by exposure to solar radiation.

[0049] As stated above, the compound of formula (I) of the invention is useful as an adjuvant for photoprotectors. Preferably, the photoprotector is fucoxanthin.

[0050] EXAMPLES

[0051] The following examples are for illustrative purposes only and should not be construed as limiting this invention.

[0052] 1. Synthesis of morin oxime, (2-(2,4-dihydroxyphenyl)-3,5,7- thhydroxy-4H-chromen-4-one oxime) and morin semicarbazone (2-(2-(2,4-

[0053] ¡l)-3,5,7-thidrox¡-4H-chromen-4-¡l¡ i-1-i

[0054] For the preparation of morin oxime, 0.03 g of morin dissolved in 5 mL of MeOH were used, 0.0206 g of hydroxylamine hydrochloride and 0.0206 g of sodium acetate were added. The mixture was left under constant stirring and reflux for 2.5 hours. After this time, the reaction crude was tempered and poured onto wet ice, generating a precipitate, which was washed with dichloromethane and methanol, obtaining a yellow solid in 60% yield. Yellow crystals were obtained, with a melting point of 290-293 °C and which are soluble in AcOEt, acetone, MeOH, and partially soluble in water. NMR 1 H 5 7.47 d (J = 8.5 Hz), 6.45 d (J = 8.5; 2.1 Hz), 6.39 d (J = 2.1 Hz), 6.34 d (J = 1.9 Hz), 6.16 d (J = 1.9 Hz). NMR of 13 C 5 102.9, 122.0, 122.0, 144.3, 149.1, 149.4, 152.8, 153.1, 154.7, 155.9, 84.5, 89.5, 95.5, 95.5, 99.5. UV(EtOH)A max(log 8) 210 (4.6), 265 (4.2), 390 (4.4). The preparation of the compound can be carried out using the above procedure with 0.1 g of morin, 0.07 g of hydroxylamine hydrochloride and 0.07 g of sodium acetate.

[0055] For the preparation of morin semicarbazone, 0.03 g of morin dissolved in 5 mL of MeOH were used, 0.0332 g of semicarbazide hydrochloride and 0.0332 g of sodium acetate were added. The mixture was left under constant stirring and reflux for 3 hours. After this time, the reaction crude was tempered and poured onto wet ice, generating a precipitate, which was recovered by filtration, obtaining a coffee solid in 76% yield. Brown crystals were obtained, with a melting point of 267-270 °C, solubility in AcOEt, acetone, MeOH. 1H (400 MHz, DMSO-d6) 12.63 s, 10.71 sa, 9.77 sa, 7.22 d (J= 8.4 Hz), 6.37 d (J= 2.4 Hz), 6.33 dd (J= 8.4; 2.4 Hz), 6.28 d (J= 1.9 Hz), 6.16 d (J= 1.9 Hz). UV (EtOH) Amax (log £) 210 (4.5), 265 (5.2), 390 (5.1). The preparation of the compound can be carried out using the aforementioned procedure with 0.1 g of morin, 0.09 g of semicarbazide hydrochloride and 0.09 g of sodium acetate.

[0056] Example 2. Comparison of the absorption spectra between morin and the compounds obtained in Example 1

[0057] As experimental evidence of the improvement in the photoprotective capacity of compounds synthesized in Example 1, a comparison was made of the absorption capacity in the UV-vis range between morin and nitrogen derivatives (Schiff bases). As can be seen in Figure 1 , the UV-vis absorption range includes a window that covers 200-500 nm, both for morin and for the compounds synthesized in Example 1 , which guarantees, at least, the absorption of UVB, UVA and UVA-vis rays, since it absorbs above 400 nm.

[0058] The tangible improvement with chemical modification for the compounds synthesized in Example 1 is evident when comparing the molar extinction coefficient (£) values. The results showed that morin oxime had the best value of 8, followed by morin semicarbazone. Upon closer analysis, it can be seen that the £m ax of morin oxime is 60% better than that of morin, and £m The ax of morin semicarbazone is 40% better than that of morin. Based on these results, it can be deduced that an equivalent of morin oxime or morin semicarbazone is more effective than one of morin in UV-vis absorption, and, therefore, lower concentrations of these derivatives are necessary to achieve UV-vis absorption values ​​similar to those of morin. Therefore, an improvement in the optimization of active ingredients used in the preparation of compositions whose purpose is directed at photoprotection and a photoabsorbing flavonoid is contemplated in said formulation can be achieved.

[0059] Example 3. Analysis of the antioxidant capacity of morin and the compounds obtained in Example 1

[0060] As mentioned above, the objective of these studies is to compare the photoprotective activity of morin, already known previously, with that of two new derivatives obtained from structural modifications of this flavonoid synthesized in Example 1.

[0061] First, the antioxidant capacity of the compounds was determined directly by the ABTS (2,2-azino-bis-3-benzo-t¡azolin-6-sulfonic acid) technique at different concentrations of the compounds (morin and the compounds of Example 1), using as a reference control a curve of increasing concentrations of Trolox. The results showed that the 2 compounds obtained in Example 1 presented an antioxidant activity similar to that of morin and in all cases superior to Trolox (Table 1).

[0062] Table 1. Antioxidant capacity of the compounds

[0063] Example 4. Study of the anti-inflammatory activity of the diester and the compounds obtained in Example 1

[0064] For the evaluation of anti-inflammatory activity (Figure 2), HaCaT keratinocytes received a 4 h pretreatment with the compounds morin (A), morin oxime obtained in Example 1 (B) and morin semicarbazone obtained in Example 1 (C) (2.5, 5 and 10 μM). Subsequently, they were irradiated with UVB radiation at 50 mJ / cm 2, were incubated for 24 h and IL-6 (interleukin-6) production was assessed by ELISA. Results were expressed as pg / mL and bars represent ± SEM (n=5). The mean was significantly different compared to non-irradiated control cells (+++ p < 0.001; Student's t-test). The mean was significantly different compared to irradiated control cells (** p < 0.01, *** p < 0.001; Kruskal-Wallis test followed by Dunn's multiple comparison test). The results showed a potent reduction in IL-6 production after treatment with the compounds of Example 1 at all concentrations tested compared to morin. Thus, it is worth noting that at the highest concentration tested (10 M), morin oxime reduced IL-6 levels by 45% (Figure 2B) and morin semicarbazone by 28% (Figure 2C), compared to morin, which showed a decrease of only 16% (Figure 2A).

[0065] Example 5. Evaluation of the antioxidant activity of morin semicarbazone For the evaluation of the antioxidant activity of the morin semicarbazone obtained in Example 1, HaCaT cells were pre-treated with morin and semicarbazone, at the selected concentrations for 4 h and then irradiated with UVB radiation at 50 mJ / cm 2. After 45 min, ROS levels were measured using the dichlorodihydrofluorescein-diacetate technique. The results of these studies showed that the semicarbazone derivative of morin reduced ROS production by up to 20% at a concentration of 10 pM (Figure 3B), compared to morin (Figure 3A), which failed to reduce ROS levels at any of the concentrations tested. The results were expressed as a percentage with respect to the irradiated cell control, and the bars represented mean ± SEM (n = 4). The mean was significantly different compared to non-irradiated control cells (+++ p < 0.001; Mann-Whitney U test). The mean was significantly different compared to irradiated control cells (* p < 0.05, ** p < 0.01; Kruskal-Wallis test followed by Dunn's multiple comparison test).

[0066] Example 6. Testing the combination of morin or semicarbazone with fucoxanthin

[0067] Once the antioxidant and anti-inflammatory activity was assessed, synergy studies were performed. To this end, the morin semicarbazone from Example 1 was selected and combined in a 1:1 ratio with fucoxanthin, a carotenoid with known photoprotective activity.

[0068] The results of this study demonstrated that the combination of the morin semicarbazone derivative of Example 1 with fucoxanthin (Figure 4C) induced greater protection of cell viability than either carotenoid alone (Figure 4A), recovering viability to healthy cell levels at all concentrations tested. Furthermore, this combination was much more effective than when fucoxanthin was used in combination with the reference compound morin, where values ​​around 70-80% were obtained (Figure 4B).

[0069] With regard to ROS production, both morin and the morin semicarbazone derivative of Example 1, combined with fucoxanthin in a 1:1 ratio, significantly reduced the levels of this marker at all concentrations tested, reaching levels comparable to those of non-irradiated cells. This decrease was slightly higher with the fucoxanthin+morin semicarbazone mixture at the 1.25-1.25 ¡JM and 2.5-2.5 ¡JM combinations (41% reduction) (Figure 5C) than with fucoxanthin+morin (33% and 37% reduction, respectively) (Figure 5B). Furthermore, it should be noted that the combination of the derivative with fucoxanthin was more effective than when fucoxanthin was used alone, with which reductions of 34% were observed at the highest concentration tested (Figure 5A). The results were expressed as a percentage with respect to the irradiated cell control and the bars represented mean ± SEM (n=4).The mean was significantly different compared to non-irradiated control cells (+++ p < 0.001; Mann-Whitney U test). The mean was significantly different compared to irradiated control cells (* p < 0.05, ** p < 0.01; Kruskal-Wallis test followed by Dunn's multiple comparison test).

[0070] Finally, the combination of morin or the morin semicarbazone derivative of Example 1 with fucoxanthin induced a decrease in IL-6 production at all concentrations tested in a 1:1 ratio. It is worth mentioning that this reduction was more notable with the fucoxanthin+morin semicarbazone mixture at the 5-5 ¡JM and 10-10 ¡JM combinations (42% reduction) (Figure 6C) than with fucoxanthin+morin (38% reduction) (Figure 6B). Furthermore, the combination of the derivative with fucoxanthin was more effective than when the carotenoid was used alone, with which reductions of 30% were observed at the highest concentration tested (Figure 6A). The results were expressed as a percentage with respect to the irradiated cell control and the bars represented mean ± SEM (n=4). The mean was significantly different compared to non-irradiated control cells (+++ p < 0.001; Student's t test).The mean was significantly different compared to irradiated control cells (*** p < 0.001; Kruskal-Wallis test followed by Dunn's multiple comparison test).

Claims

CLAIMS 1. A compound of formula (I) Formula (I) where R is selected from: a saturated, linear or branched Ci-Ce alkyl radical, a linear or branched C2-C6 alkenyl radical; a linear or branched C2-C6 alkynyl radical, a C3-C12 cycloalkyl radical, a C3-C12 aryl radical, a -XR radical 1 , a radical -NHC=XNR 2 R 3 , a radical -NHR 4 , a radical -NHCOOR 5 , a radical -NHCOR 6 ; where X is selected from O, S; where R 1 , R 2 R 3 , R 4 , R 5 , and R 6 They may be the same or different and are selected from H, a saturated, linear or branched C1-C2 alkyl radical, a linear or branched C2-C6 alkenyl radical; a linear or branched C2-C6 alkynyl radical, a C3-C6 cycloalkyl radical, a C3-C6 aryl radical.

2. The compound of formula (I) characterized in that it is morin oxime, (2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one oxime).

3. The compound of formula (I) characterized in that it is the morin semicarbazone, (2-(2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-ylidene)hydrazine-1-carboxamide).

4. A process for obtaining compounds of general formula (I) as defined in claim 1 Formula (I) comprising the steps of: reacting 2-(2,4-dihydroxyphenyl)-3,5,7-thhydroxy-4H-chromen-4-one, of formula (II) Formula (II) with a nitrogen compound of formula H2NR, in the presence of an organic solvent; where R is selected from: a saturated, linear or branched Ci-Ce alkyl radical, a linear or branched C2-C6 alkenyl radical; a linear or branched C2-C6 alkynyl radical, a C3-C12 cycloalkyl radical, a C3-C12 aryl radical, a -XR radical1 , a radical -NHC=XNR 2 R 3 , a radical -NHR 4 , a radical -NHCOOR 5 , a radical -NHCOR 6 ; where X is selected from O, S; where R 1 , R 2 R 3 , R 4 , R 5 , and R 6 They may be the same or different and are selected from H, a saturated, linear or branched C1-C2 alkyl radical, a linear or branched C2-C6 alkenyl radical; a linear or branched C2-C6 alkynyl radical, a C3-C6 cycloalkyl radical, a C3-C6 aryl radical.

5. The process for obtaining the compounds of formula (I) according to claim 4, characterized in that the nitrogen compound that reacts with the compound of formula (II) is hydroxylamine hydrochloride or semicarbazide hydrochloride.

6. The production process according to claim 4 or 5, characterized in that the organic solvent is methanol.

7. Use of a product of formula (I) according to claim 1 in the preparation of a cosmetic or dermatological composition to protect a mammal from UV-vis radiation.

8. Compound of formula (I) according to any of claims 1 to 3 for use in medicine or dermocosmetics.

9. Compound of formula (I) according to any of claims 1 to 3 for use in protecting a mammal from UV-vis radiation.

10. Compound of formula (I) according to any of claims 1 to 3 for use in the prevention of skin cancer.

11. Compound of formula (I) according to any of claims 1 to 3 for use in preventing inflammation, oxidative stress and skin aging.

12. Compound of formula (I) according to any of claims 1 to 3 for use as an adjuvant for photoprotectors.

13. Compound of formula (I) according to claim 12, wherein the photoprotector is fucoxanthin.

14. Cosmetic composition or dermatological composition comprising the product of formula (I) according to any of claims 1 to 3.

15. Cosmetic composition or dermatological composition comprising (2-(2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-ylidene)hydrazine-1-carboxamide) and fucoxanthin.

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