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Jesus, A.; Sousa, M.E.; Rosete, M.T.; Cidade, H.; Sousa Lobo, J.M.; Almeida, I. UV Filters. Encyclopedia. Available online: https://encyclopedia.pub/entry/21312 (accessed on 05 May 2024).
Jesus A, Sousa ME, Rosete MT, Cidade H, Sousa Lobo JM, Almeida I. UV Filters. Encyclopedia. Available at: https://encyclopedia.pub/entry/21312. Accessed May 05, 2024.
Jesus, Ana, Maria Emília Sousa, Maria Teresa Rosete, Honorina Cidade, José Manuel Sousa Lobo, Isabel Almeida. "UV Filters" Encyclopedia, https://encyclopedia.pub/entry/21312 (accessed May 05, 2024).
Jesus, A., Sousa, M.E., Rosete, M.T., Cidade, H., Sousa Lobo, J.M., & Almeida, I. (2022, April 02). UV Filters. In Encyclopedia. https://encyclopedia.pub/entry/21312
Jesus, Ana, et al. "UV Filters." Encyclopedia. Web. 02 April, 2022.
UV Filters
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This entry is adapted from the peer-reviewed paper 10.3390/ph15030263

The use of sunscreens is a recommended practice to protect skin from solar-induced damage. Around 30 UV filters can be used in sunscreen products in the European Union. However, low photostability and putative toxicity for humans and environment have been reported for some UV filters. Therefore, it is important to develop new UV filters with improved safety profile and photostability. Over the last two decades, nearly 200 new compounds have revealed promising photoprotection properties. The explored compounds were obtained through different approaches, including exploration of natural sources, synthetic pathways, and nanotechnology. Almost 50 natural products and around 140 synthetic derivatives have been studied aiming the discovery of novel, effective, and safer future photoprotective agents. 

UV filters challenges toxicity photostability prospects natural products synthetic derivatives

1. Introduction

Sunlight has several beneficial effects in human, such as the production of vitamin D, and induction of β-endorphin expression, which improve well-being [1]. However, excessive sunlight exposure is responsible for photo-induced skin damage, namely solar sunburn, hyperpigmentation, photoaging, skin photosensitisation, and skin cancer [2], when protective measures, namely the use of sunscreen and the use of adequate clothes and accessories, are not adopted [3]. Photoprotective measures are more ancient than the first sunscreen’s appearance in the 1900s, and ancient civilisations used plant extracts to protect their skin from sunburns for a long time [4]. Many of the chemical compounds present in natural extracts with photoprotective properties are now part of sunscreens . In fact, most of UV filters are inspired in natural products, specifically of botanical, animal, or mineral origin [5]. In 1928, benzyl salicylate was discovery for its photoprotective action against UVB radiation, but it was only commercialised in 1935 in the first sunscreen “Ambre Solaire” [6][7]. Later, almost 50 years, avobenzone and its derivatives appeared as the first UV filters that ensure protection against UVA radiation [8]. Currently, in Europe, there are a total of 29 approved UV filters [9], complying with the regulations that ensure their effectiveness and safety for humans. UV filters can be classified concerning their ability to absorb the UV radiation (UVR), as UVA, UVB or broad-spectrum UV filters (UVA and UVB) [10]. Additionally, these products can also be branched into organic or inorganic, where organic filters are only capable to absorb the UVR, while inorganic filters can reflect and scatter the UVR [10]. In recent decades, the safety of UV filters for humans and environment has been called into question. In fact, many studies have confirmed the detection of UV filters in human biological samples [11][12] and in marine organisms [13][14][15][16], thus confirming the hypothesis of UV filter-derived toxic effects. The presence of particular chemical moieties in UV filter structures confers intrinsic toxicity [17][18]. Photoinstability occurs for UV filters that photoisomerise or photodegrade, and consequently can generate toxic photodegradation products and loss of photoprotective action [19]. Therefore, over the last two decades, new natural products from botanical and marine sources [20][21][22] and synthetic derivatives [23][24][25][24] have been investigated, along with the use of nanotechnology approaches [26] as strategies to find new, more effective, safer and more stable UV filters.

2. Challenges

The main challenges associated with the UV filters present in sunscreens are their photoinstability, environmental impact, and human toxicity. As mentioned before, these are some points to consider in the development of new effective and safer photoprotective agents.
The stability of sunscreens is an essential requisite to ensure photoprotection and safety. UV filters absorb UVR and enter in excited energetic levels [27]. Then, the energy is released, and the chemical molecule returns to its initial energetic level. During this process, some UV filters undergo photoisomerisation and even irreversible cleavage of bonds [28]. The mechanisms associated with this phenomenon include the formation of photodegradation products, which can negatively influence the sunscreen’s effectiveness. These degraded derivatives could also be toxic due to interaction with the constituents present in cells and/or damage the DNA. Moreover, they can also affect the stability of the other ingredients present in the formulation [28].
Several approaches could be used in order to ameliorate the photostability of photoprotective agents, such as the introduction of antioxidants [29], encapsulation [30], multiple association of UV filters [31][32][33], and the addition of quenching molecules [34] in the sunscreen’s formulation [35][36].
The concern about the negative impact of UV filters on environment and organisms is growing day-by-day. The research community is trying to find alternatives and solutions to minimise the risks posed by these actual emergent pollutants [37]. The impact that sunscreen agents could have in organisms is relevant, namely in marine organisms. Recently, several studies revealed the dangerous and noxious effects of UV filters towards diverse aquatic species, such as mussels [38][39], algae [40], crustaceans [40], corals [41][42][43], sea urchins [40], fish [44], and even in dolphins [45]. There are two ways of studying the toxicological effects in marine organisms: by determining the concentration of UV filters in a specific organism, by collecting the marine organism in the environment, or through the organism’s exposure to a specific range of UV filters’ concentrations and subsequently verifying the effects [16]. In the next sections, the possible effects that UV filters may have in human beings and in the environment, namely in marine organisms, will be described. Figure 1 depicts the main human systems and marine organisms that suffer the negative impact of the UV filter’s toxicity.
Figure 1. Resume of the main systems affected by UV filter’s toxicity.
The occurrence of UV filters in different locations worldwide with concentration values between ng/L and µg/L has been studied in lakes, seawaters, sediments, rivers, estuaries, and in aquatic organisms [46]. In fact, the harmful effects of UV radiation leaded to an extensive production and use of photoprotective products during vacancies, which resulted in an increase in UV filters present in an environment, namely in aquatic ecosystems [46]. The contamination of terrestrial environment could also occurred by wastewaters discharges, disposal of product packages in inappropriate locations, and even in indoor dust that drives to an environment issue, contaminating both land and terrestrial organisms [47]. Bioaccumulation and toxicological effects are the main issues associated with marine contamination by UV filters that could induce the persistence of these emergent contaminants through the food chain [47]. Considering the relevance of this topic, herein some studies reporting the bioaccumulation and negative impact of UV filters in marine organisms are discussed.

3. Prospects

Several improvements in sunscreens were made in recent decades, particularly aiming to obtain new UV filters with increased photoprotective effectiveness, photostability, environmental and human safety, and improved sensory properties [48]. With this purpose, many sources have been explored by the scientific community, namely extracts and natural products isolated from both terrestrial and marine sources and new synthetic derivatives.

3.1. Nature as a Source of Potential Photoprotective Agents and UV Filters

Nature has been widely used for many decades, as the main source for the discovery of new bioactive compounds. Considering skin care applications, several botanical and marine organisms’ extracts with photoprotective and antioxidant effects have been reported. Additionally, some natural products isolated from these sources have proved to be promising bioactive compounds.
Every day, plants are exposed to UVR, which increases their resistance to the noxious UV rays. As a result of this natural resistance, secondary metabolites with diversified scaffolds possessing UV photoprotective and antioxidant properties are produced, specially terpenoids, anthocyanins, flavonoids, carotenoids, and phenolic acids [20]. Algae, cyanobacteria, bacteria, and marine fungi are some of examples of marine organisms that produce secondary metabolites with photoprotective effects through UV filter and antioxidant activity. In Table 1, natural extracts and metabolites (36–56) of botanical and marine sources with photoprotective and antioxidant activities are presented.
to be the most promising compounds obtained from botanical extracts, considering their good photostability, photoprotective, antioxidant potential, and non-cytotoxic profile at the concentrations mentioned. Interestingly, the presence of hydroxyl groups is a common structure feature for the most promising secondary metabolites with antioxidant activity. Considering marine-derived metabolites, MAAs, palythine (41), asterina-330 (42), shinorine (43), porphyra-334 (45), and scytonemin (44) have an excellent protective ability against UVR, being 44 an UVA/UVB absorber. Comparing both botanical and marine natural sources, marine-derived extracts and metabolites possess improved ability to protect against photo-induced damage. The antioxidant potential and easily introduction in cosmetic formulations are the main strengths of botanical extracts and metabolites. Despite all the advances on analytic techniques, it is not always possible to identify the active metabolite. Moreover, the isolation and purification of the botanical and marine natural products with photoprotective activity is a time-consuming process, being obtained in a low amount, which is a major drawback for obtaining compounds to be further explored for skin care applications. Therefore, some of these natural products were used as lead compounds to obtain synthetic derivatives with promising photoprotective effects.
Table 1. Natural extracts and metabolites of botanical and marine sources with photoprotective and antioxidant activity.
Organism and Species Main Identified Secondary Metabolites Activity Values References
Botanical Extracts and Metabolites
Methanolic extract of grape seeds (from Village Farm and Winery; Nakhon Ratchasima, Thailand) (+)-catechin (36) and (-)-epicatechin (37) (determined by HPLC)
Pharmaceuticals 15 00263 i007		 Photoprotective (% cell viability) At 25 μg/mL
10 J/cm2 (110%)
20 J/cm2 (68%)		 [33]
Photodegradation 36 = 35.1%; 37 = 31.3%
Combination with UV filter: 36 (4.6%); 37 (7.0%)
Hydroethanolic extract of Vitis vinifera L. Flavonoids, phenolic compounds, procyanidins, among others (determined by HPLC) Antioxidant (DPPH) at 1mg/mL 707.00 ± 0.03 µmol/g (pH = 5)
1098.00 ± 0.01 µmol/g (pH = 7)		 [34]
Photoprotection SPF = 20–76
λc = 360–381 nm (pH = 5)
Ethanolic commercial extract of olive leaves 20% of oleuropein (38)
Pharmaceuticals 15 00263 i008		 Antioxidant (DPPH) 38: IC50 = 11.75 ± 1.01 μg/mL
Extract: IC50 = 13.8 ± 0.8 μg/mL		 [35]
Photoprotective λmax = 376 nm
SPF = 22
Ethanolic Extract of varied Lippia species (L. brasiliensis, L. rotundifolia, L. rubella and L. sericea) Phenols and flavonoids Antioxidant (DPPH) IC50 = 0.604 mg/mL [36]
Photoprotective SPF = 1.7–7.6 (formulation with 10% of the extract)
λc = 375 nm
Ethanolic extract of Amazonian Cecropia obtusa leaves Polyphenols Antioxidant IC50 = 1.63 µg/mL (DPPH)
IC50 = 0.34 µg/mL(O2−)
IC50 = 0.55 µg/mL(1O2)		 [37]
Photoprotective SPF = 16
Cytotoxicity (HaCaT keratinocyte cell line) At 20 µg/mL: cell viability = 100%
Ethanolic extract of Acacia catechu heartwood - Photoprotective SPF = 24–30 [38]
Hydroalcoholic extract of five wild Brazilian bamboo species (Chusqueaspp., Aulonemia aristulata, and Merostachys pluriflora) Phenolic compounds Antioxidant (DPPH) IC50 = 137.55–260 μg/mL [39]
Photoprotective SPF (before irradiation) = 34–86
SPF (after irradiation)
= 14–44
Dichloromethane/acetone (1:1) extract from Lasallia pustulata Lichenic metabolites, being gyrophoric acid (39)
identified by HPLC
Pharmaceuticals 15 00263 i009		 Antioxidant (DPPH) 25 % at 500 µg/mL [40]
Photoprotective λmax = 300 nm
SPF = 5.03
Cytotoxicity (HaCaT keratinocytes cell line) IC50 = 168 ± 33 µg/mL (before radiation)
IC50 > 200 µg/mL (after radiation)
Wood powder - Photoprotective SPF = 11 (formulation)
SPF = 37 (formulation + 5% of wood powder)		 [41]
Ethanolic extracts of Alpinia galanga, Curcuma longa and Aloe vera Flavonoids, phenols and terpenoids Photoprotective SPF = 18.2 (extract of C. longa)
λmax = 290 nm (C. longa)
SPF = 15.1 (A. galanga)
λmax = 290 nm (A. galanga)		 [42]
Coconut oil High quantity of saturated fatty acids Photoprotective λmax = 205 nm (coconut oil)
λmax = 320 nm (coconut oil + BP-3)		 [43]
Resveratrol (40) and ethanolic extract of green tea Resveratrol (40)
Pharmaceuticals 15 00263 i010		 Antioxidant (DPPH) IC50 = 38.67–85.44 % (resveratrol)
IC50 = 37.41–77.50 % (green tea extract)		 [44]
Photoprotective λmax = 310 nm (40)
λmax = 270 nm (green tea)
SPF = 9.35 (40)
SPF = 14.59 (green tea extract)
SPF = 16.91 (40 and green tea extract)
Marine Organisms Extracts and Metabolites
Methanolic extract of red macroalgae Curdiea racovitzae and Iridaea cordata MAAs, with major quantity of palythine (41), asterina-330 (42), and shinorine (43)
Pharmaceuticals 15 00263 i011		 Antioxidant (DPPH) IC50 = 970.00 μg/mL (C. racovitzae)
IC50 = 2960.00 μg/mL (I. cordata)		 [45]
Photoprotective λmax = 320 nm (both)
λc = 356 nm (C. racovitzae)
λc = 347 nm (I. cordata)
Cytotoxicity (HaCaT keratinocytes cell line) At 1 mg/mL
% cell viability = 89 (C. racovitzae)
% cell viability = 73 (I. cordata)
Ethanolic extract of brown macroalgae Sargassum cristafolium Palythine (41) Photoprotective λc = 370 nm [49]
Methanolic extract red alga Corallina pilulifera - Antioxidant (DPPH) At 200 mg/mL: 80% scaveging activity [50]
Metabolite from extracts of cyanobacteria Stigonema sp., Scytonema sp. and Lyngbya sp. Scytonemin (44)
Pharmaceuticals 15 00263 i012		 Photoprotective λmax = 252, 278, 300, 386 nm [51]
Metabolites from aqueous methanolic extract of cyanobacteria Microcystis aeruginosa MAAs shinorine (43) and porphyra-334 (45)
Pharmaceuticals 15 00263 i013		 Photoprotective λmax = 334 nm [52]
Metabolites from ethyl acetate extract of marine fungi Penicillium echinulatum Quinolinic Alkaloids
Pharmaceuticals 15 00263 i014		 Photoprotective λmax = 287 (48)
λc = 335 nm (48)
λmax = 330 (49)
λc = 334 nm (49)		 [53]
Phototoxicity (HaCaT keratinocytes cells) Reduction of ROS (43%) at 200 µg/mL (49)
Metabolites from dichloromethane/methanol (2:1) extract of algae Bostrychia radicans -associated fungi Annulohypoxylon stygium Pharmaceuticals 15 00263 i015 Phototoxicity (3T3 murine fibroblasts) PIF = 1.00 (50 and 51)
PIF = 5.2 (54)		 [54]
Metabolite from ethanolic extract of plant Thalassia testudinum Thalassiolin B (55)
Pharmaceuticals 15 00263 i016		 Antioxidant (DPPH) IC50 = 100 μg/mL [55]
Repair of Acute UVB-Damaged Skin Skin damage suppression (with 55 at 240 μg/cm2) = 90%
Platyfish Xiphophorus metabolite Melanin (56)
Pharmaceuticals 15 00263 i017		 Photo-repair of the skin Stimulate the production of melanin, which reduced the formation of pyrimidine dimers. [56]
Abbreviations: DPPH—2,2-diphenyl-1-picrylhydrazyl; SPF–solar factor protection; λc—critical wavelength; λmax—maximum wavelength; IC50—concentration that reduces a response to 50% of its maximum; HPLC—high-performance liquid chromatography; PIF—photoirritation factor.

3.2. Synthetic Derivatives with Photoprotective and UV Filter Activity

3.2.1. Inorganic UV Filters

Cerium oxide (CeO2) was suggested as one possible UV filter. In fact, it is commercialised in some photoprotective formulations but with silica coating, due to its high photocatalytic activity, responsible for oxidation and degradation of other formulations’ components [49]. The coating with amorphous silica also decreases its photoprotective UV-shielding potential [50]. However, this gap could be ameliorated if CeO2 was doped with Ca2+ and Zn2+ ions, which could reduce its photocatalytic activity and particle size, without interfering with its photoprotective potential [50]. Cerium phosphate (CePO4) was reported 10 years later by Seixas and Serra (2014) [50]. Similarly to CeO2, CePO4 was described for possessing high photocatalytic activity, low amount of white residue when applied on the skin, and increased stability. Some parameters regarding physical and chemical stability of CePO4 were evaluated, using TiO2 (34) and ZnO (35) as controls, as well as its behavioural and rheological properties, both alone and in formulation. The results revealed low interaction in formulation when combined with organic UV filters. Therefore, CePO4 is a potential future novel, stable, and efficient inorganic UV filter [50].

3.2.2. Organic UV Filters

Inspired by commercialised UV filters, as well as in natural products with photoprotective properties, several compounds have been synthesised and reported as potential UV filters, with antioxidant, anti-inflammatory, and anti-photoaging activities. Herein, a reference of the novel synthetic derivatives developed with the aim of obtaining UV filtering compounds with extra pharmacological properties are presented. Figure 2 presents the chemical skeleton, and the range of values obtained for the biological activity assessed.
Figure 2. Chemical skeleton and values of biological activity assessed for the synthetic derivatives reported in the literature.

3.2.2.1. New Synthetic Derivatives Inspired by Commercialised UV Filters

One of the strategies followed by research groups to obtain new organic UV filters with improved photoprotective activity is through molecular modifications of actually marketed UV filters. Eight octocrylene (30)-related compounds (57–64) were prepared and evaluated for their photoprotective effect by Polonini et al. (2014) [51]. Among these, 60, 61, and 63 displayed the best UVB protection effect, while compounds 61–63 presented the best results concerning protection against UVA. The most promising derivative was 63, which behaved as a broad band UVA/UVB filter [51].
Using benzophenone derivatives as lead compounds, benzophenones 65–68 were prepared and tested for their UV filtering properties [52].Compounds 65 and 66 were considered as the most promising, showing photoprotective activity and non-phototoxic results, confirmed by PIF values as less than 1.3. In addition to these benzophenones, the structure-related benzophenone 69 and lactone 70 displayed UV filter properties, having lactone 70, a more potent photoprotective effect (SPF = 16), but only ability to absorb UVB radiation, contrarily to benzophenone 69, which demonstrated the ability to absorb UVA radiation [53].
Later, new PABA derivatives, PABA methyl ester (71) and PABA methyl stearate (72), were prepared and evaluated for their photoprotective potential, revealing SPF values of 20.60 and 26.17, respectively [54]. It is noteworthy to mention that the high molecular weight of 72 should avoid its penetration through the skin, making this compound a potential UV filter with a safer profile.
Inspired by benzimidazole and benzotriazole approved UV filters, several new heterocyclic compounds were prepared. Benzimidazole derivatives 73–86 were reported for their photoprotective activity, and compound 83 also demonstrated antioxidant activity and higher photostability (98.4%) when compared with the control phenylbenzimidazole sulfonic acid (PBSA) (14) (96.7%) [55]. Additionally, new 5-membered ring-benzimidazole derivatives (87–89) were also prepared, being compounds with pyrrole (87), furan (88), and thiophene (89) moieties which were the most promising regarding their antioxidant, photostability, and photoprotective activities [56]. Among these, the most photostable was the thiophene derivative 89, followed by pyrrole derivative 87, and the furan derivative 88 [56].
Using triazine UV filters as models, new 1,3,5-triazine derivatives (90–97) were synthesised and evaluated for their photoprotective properties [57]. Among 1,3,5-triazine derivatives 90–97, 97 displayed the most promising antioxidant activity and revealed the highest SPF and UVA protection factor [57].
Inspired in 3-benzylidenecamphor (7), Popiół et al. (2019) planned a small library of potential UV filters (98110) by replacing the camphor moiety by 5-arylideneimidazolidine-2,4-dione (hydantoin) while maintaining the benzylidene portion. Although the synthesised compounds revealed moderate SPF values, they demonstrated the ability to absorb both UVA and UVB radiation (λc between 339 and 391 nm) [57]. Compounds 104 and 109 were considered the less toxic against HaCaT keratinocytes and human fibroblasts cell lines, and compound 99 revealed the best UVB photoprotective properties within the tested series, with a SPF = 4.7. Some structure–activity relationships (SAR) considerations could be drawn for these derivatives. For instance, methoxy substituents at the aromatic ring are associated with photoprotection against UVA radiation; in contrast, the absence of methoxy groups in the aromatic ring is associated with interesting UVB filter properties [57]. In addition, the presence of alkoxy groups at positions 4- (compounds 99, 104, and 109) and 3,4- (compounds 102 and 107) is associated with the highest values of critical wavelength, contrarily to what is observed with non-substituted benzene rings [57].
Sinapic acid analogues of EHMC (21) with ester (111–124), amide (125–126), and ketone (127) groups revealed promising UV filter activity. Interestingly, 111 and 114–127 showed multifunctional properties, combining antioxidant and photoprotective effects. Among all compounds, the derivatives 125 and 127 showed the best antioxidant activities with IC50 values lower than 8.9 ± 0.3 nmol [58]. Additionally, sinapic acid analogue 111 and its methylated derivative 112, aliphatic sinapate derivatives 116 and 118, and amide derivative 125 presented higher photostability than EHMC (21) [58].
Molecular hybridisation avobenzone (11), EHMC (21), and trans-resveratrol (40) resulted in the identification of a novel series of hybrids (128–135) with UV filter effect [59]. All compounds revealed photoprotective activity with SPF values varied between 2 and 5, and an ability to absorb the UVA region of the electromagnetic spectrum, confirmed by their λmax values in the range of 369 nm and 389 nm [59]. Additionally, three hybrids of the total synthetised compounds 128–135 possess antioxidant potential, with an IC50 between 88 µM and 275 µM (compounds 128, 134, and 135) [59]. Amongst all, compounds 128 and 131–135 possess characteristics of broad-spectrum molecules, having 128, 134, and 135 an interesting DPPH radical scavenging activity.

3.2.2.2. Nature-Inspired Synthetised Compounds

Naturally occurring stilbenes, p-hydroxycinnamic acids, and xanthones have been used as inspiration to obtain new potential UV filters. Inspired in the photoprotective activity of trans-resveratrol (40), compounds 126–141 were prepared and tested for their UV filter effect. All compounds revealed promising UV filter properties, with SPF values between 2 and 20 [59].
Sinapoyl-L-malate (142) is a sinapoyl ester widely described for its UV protection in plants [60]. Taking this into account, the UV filter activity of sinapoyl-L-malate 142 and its analogues 143–157 were explored by Peyrot et al. (2020) [61]. All compounds presented good water solubility, as a result of the presence of a free carboxylic acid in their structure which could facilitate the incorporation into sunscreen’s formulation. Among all the compounds, 142–157, 142, 144, 147, and 150–157 showed promising photoprotective activity with LoA < avobenzone (11), and antioxidant activity, being 151 and 155–157 the most promising. Moreover, 142, 151, and 154–157 revealed photostability with LoA values less than 20% [61].
Based in natural-inspired p-hydroxycinnamic acids, p-hydroxycinnamic diacids were prepared (158–161), being sinapic diacid (160) and caffeic diacid (161) the derivatives that displayed the best photoprotective characteristics [62].
Xanthone derivatives were studied in order to disclose their profiles as future UV filtering molecules. Resende et al. (2020) reported three hydroxylated xanthone derivatives (162–164) with promising antioxidant activity and UV filtering characteristics [63]. Compounds 162–164 proved to absorb in the UVB range (280–320 nm). Additionally, xanthone 162 showed a dual ability to protect the skin against UV damage, through DPPH scavenging action and UV-filter capacity, without phototoxicity in the HaCaT keratinocyte cell line [63]. Popiół et al. (2021) also reported novel potential and innovative UV filtering compounds, combining the xanthone scaffold with €-cinnamoyl moiety [61]. Active xanthone-cinnamoyl hybrid compounds 165 and 166 were synthetised and evaluated for their photoprotective, antioxidant, and mutagenic activities [22]. Compound 166 was revealed to be the most promising, displaying λc of 381 nm, confirming the ability to absorb both UVA and UVB radiations and with a SPF of 19.69 [61]. Comparing these two groups of xanthones, the combination of the cinnamoyl and xanthonic moieties allows the correct electronic delocalisation, which improves the UV absorber properties and, because of that, compounds reported by Popiół et al. [61] possess action against UVA and UVB radiation, in contrast to compounds with a simple xanthone scaffold reported by Resende et al. [63].

3.2.2.3. Other New Synthetic Derivatives

Other potential synthetic UV filters with different scaffolds have been described, namely those with heterocyclic rings, such as the new UV absorbers 167–178 based on quinoline derivatives with SPF and λc values between 2 and 11 and 376 and 388 nm, respectively, being the quinoline derivative 176 considered as the most promising compound with the highest SPF value [63]. (E,Z)-2-ethylhexyl-2-cyano-3-(furan-2-yl)acrylate (179) has also been described for its good capacity to absorb UVA radiation (λmax = 339 nm) and good solubility in oils for the formulation [64].
Recently, Peyrot et al. (2020) developed a small library of compounds from Meldrum’s acid and p-hydroxycinnamic acids (180–183), furans (184–190), and pyrroles (191–193), displaying interesting UV filter properties and photostability. Moreover, p-hydroxycinnamic acid-based Meldrum’s derivatives (180 and 183) possess antioxidant and anti-tyrosinase properties, photoprotective characteristics, namely against UVA radiation and blue light, and photostability (with LoA < avobenzone (11)) [61] reinforcing their potential as multifunctional agents for cosmetic application. Interestingly, endocrine disruption assays were performed for compounds 182, 184, 187, and 191, that revealed non-interaction with receptors, showing the absence of agonistic (% receptor activity < 30%) and antagonistic (% receptor activity > 70%) effects [61].

4. Conclusions

Ultraviolet filters are incorporated in sunscreens aiming to protect the skin from the noxious effects of UV rays. Despite the strict regulation framework, new scientific evidences have raised concern about their toxic effects in humans and marine ecosystems. Neurotoxicity, endocrine disruption, malformations, decreased photosynthetic pigments, coral bleaching, and mortality, among others, are some of the confirmed negative effects that some UV filters, namely benzophenone-3, avobenzone, EHMC, and octocrylene can have in marine organisms. The decomposition of the UV filters detected in aquatic ambient was already reported, leading to the formation of toxic by-products with putative negative effects for human beings and accumulation in marine organisms. Beyond these environmental problems, UV filters can also have direct negative effects on humans, especially when photodegradation/photoisomerisation occurs. Avobenzone is the UV filter most studied regarding to its photoinstability and negative effects, hence being one of the most toxic UV filters when exposed to UV radiation. The presence of certain chemical groups, such as aromatic ketones, unsaturated systems, and camphor structure, are some of the chemical moieties susceptible of inducing allergic and sensitisation skin reactions.
Considering the mentioned pitfalls, the scientific community has been focused on creating new UV filters. The presence of labile groups suitable for hydrolysis degradation could be an approach, known in pharmaceutical sciences as “soft drugs”, aiming towards the degradation of the parent compound into inactive metabolites avoiding the oxidative pathway, and contributing to a decrease in bioaccumulation and toxicity.
The existence of privileged structures in nature, produced by plants and marine organisms, is vastly known. Natural products could be directly used, after their extraction, or could inspire the creative mind of the scientists to obtain synthetic derivatives with improved efficacy and safer profile. Botanical extracts and metabolites, namely catechin, epicatechin, gyrophoric acid, and resveratrol are some of the plant-derived metabolites that could be highlighted for their photoprotective ability, but especially for their antioxidant potential due to the presence of hydroxyl groups in their structure. In addition to botanical extracts, marine secondary metabolites also exhibit photoprotection properties, namely MAAs, which are able to absorb both UVA and UVB radiation. Some derivatives inspired by marketed UV filters were also developed to overcome some of their drawbacks. To conclude, the development of innovative, safe, effective, and non-toxic UV filters is an ongoing need and a hot research topic.

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Subjects: Pharmacology & Pharmacy
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Ana Jesus
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Maria Emília Sousa
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Maria Teresa Rosete
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Honorina Cidade
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José Manuel Sousa Lobo
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Isabel Almeida
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