Computer-aided drug design supporting sunscreen research: a showcase study using previously synthesized hybrid UV filter-antioxidant compounds.

CONTEXT: Although quantum mechanical calculations have proven effective in accurately predicting UV absorption and assessing the antioxidant potential of compounds, the utilization of computer-aided drug design (CADD) to support sustainable synthesis research of new sunscreen active ingredients remains an area with limited exploration. Furthermore, there are ongoing concerns about the safety and effectiveness of existing sunscreens. Therefore, it remains crucial to investigate photoprotection mechanisms and develop enhanced strategies for mitigating the harmful effects of UVR exposure, improving both the safety and efficacy of sunscreen products. A previous study conducted synthesis research on eight novel hybrid compounds (I-VIII) for use in sunscreen products by molecular hybridization of trans-resveratrol (RESV), avobenzone (AVO), and octinoxate (OMC). Herein, time-dependent density functional theory (TD-DFT) calculations performed in the gas phase on the isolated hybrid compounds (I-VIII) proved to reproduce the experimental UV absorption. Resveratrol-avobenzone structure-based hybrids (I-IV) present absorption maxima in the UVB range with slight differences between them, while resveratrol-OMC structure-based hybrids (V-VIII) showed main absorption in the UVA range. Among RESV-OMC hybrids, compounds V and VI exhibited higher UV absorption intensity, and compound VIII stood out for its broad-spectrum coverage in our simulations. Furthermore, both in silico and in vitro analyses revealed that compounds VII and VIII exhibited the highest antioxidant activity, with compound I emerging as the most reactive antioxidant within RESV-AVO hybrids. The study suggests a preference for the hydrogen atom transfer (HAT) mechanism over single-electron transfer followed by proton transfer (SET-PT) in the gas phase. With a strong focus on sustainability, this approach reduces costs and minimizes effluent production in synthesis research, promoting the eco-friendly development of new sunscreen active ingredients. METHODS: The SPARTAN'20 program was utilized for the geometry optimization and energy calculations of all compounds. Conformer distribution analysis was performed using the Merck molecular force field 94 (MMFF94), and geometry optimization was carried out using the parametric method 6 (PM6) followed by density functional theory (DFT/B3LYP/6-31G(d)). The antioxidant behavior of the hybrid compounds (I-VIII) was determined using the highest occupied molecular orbital (εHOMO) and the lowest unoccupied molecular orbital (εLUMO) energies, as well as the bond dissociation enthalpy (BDE), ionization potential (IP), and proton dissociation enthalpy (PDE) values, all calculated at the same level of structural optimization. TD-DFT study is carried out to calculate the excitation energy using the B3LYP functional with the 6-31G(d) basis set. The calculated transitions were convoluted with a Gaussian profile using the Gabedit program.

Analysis of the UV filter Benzophenone-3 assimilation in Crossostrea gigas oysters post-exposure in a controlled environment by LC-MS/MS.

Benzophenone-3 (BP-3), utilized as a UV filter in cosmetic products, is an emerging contaminant that constitutes a threat to natural resources and environmental health. This study investigated the assimilation of the UV filter BP-3 in Crassostrea gigas oysters collected in Florianópolis, Santa Catarina, Brazil. Lyophilized oyster tissue extracts were prepared using the QuEChERS method, and LC-MS/MS was employed to determine the BP-3 concentration in the samples. The method was applied to specimens intentionally exposed to two concentrations of the contaminant, for different periods of exposure (1 and 7 days). Samples from treatment 1 (T1) were exposed to a concentration of 1 µg L-1 of the BP-3 standard, and samples from treatment 2 (T2) were exposed to a concentration of 100 µg L-1 of the BP-3 standard. The results revealed rapid absorption of BP-3, with an increase of 126% for lower concentrations, reaching 1.13 µg of BP-3 per gram of oyster tissue, and 17% for higher concentrations, reaching 34.6 µg of BP-3 per gram of oyster tissue after 7 days. The presence of BP-3 even in samples not directly exposed to the contaminant indicates its widespread environmental distribution. The rapid bioaccumulation suggests the need to consider seasonal variations, such as increased tourism in the summer. The validated analytical method demonstrated efficacy in quantifying BP-3, providing an integrated approach for long-term monitoring of pollution levels and their dynamic variations over time. In addition, variation in BP-3 levels in the samples may be related to transport patterns influenced by tides and discharges from septic system, highlighting the need to improve wastewater treatment. These findings underscore the necessity for continuous biomonitoring and effective environmental management to safeguard the health of marine ecosystems and humans.

Inorganic UV filter-based sunscreens labelled as eco-friendly threaten sea urchin populations.

Although the negative effects of inorganic UV filters have been documented on several marine organisms, sunscreen products containing such filters are available in the market and proposed as eco-friendly substitutes for harmful, and already banned, organic UV filters (e.g. octinoxate and oxybenzone). In the present study, we investigated the effects of four sunscreen products, labelled by cosmetic companies as "eco-friendly", on the early developmental stages of the sea urchin Paracentrotus lividus, a keystone species occurring in vulnerable coastal habitats. Among sunscreens tested, those containing ZnO and TiO2 or their mix caused severe impacts on sea urchin embryos. We show that inorganic UV filters were incorporated by larvae during their development and, despite the activation of defence strategies (e.g. phagocytosis by coelomocytes), generated anomalies such as skeletal malformations and tissue necrosis. Conversely, the sunscreen product containing only new-generation organic UV filters (e.g. methylene bis-benzotriazolyl tetramethyl, ethylhexyl triazone, butylphenol diethylamino hydroxybenzoyl hexyl benzoate) did not affect sea urchins, thus resulting actually eco-compatible. Our findings expand information on the impact of inorganic UV filters on marine life, corroborate the need to improve the eco-friendliness assessment of sunscreen products and warn of the risk of bioaccumulation and potential biomagnification of inorganic UV filters along the marine food chain.

New trends on personalized sunscreens.

BACKGROUND/PURPOSE: Nowadays, there are emerging trends in customized and personalized photoprotection, focusing on the innovative approaches to enhance sun protection efficacy tailored to individual needs. METHODS: We conducted an electronic search of the following databases: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Skin Group Specialised Skin Register, and TESEO. Specific search terms related to personalized photoprotection and the variables of age, genetic predisposition, skin phototype, photodermatosis, and physiological conditions such as pregnancy, as well as lifestyle habits were used. RESULTS/CONCLUSION: The article highlights the challenges and opportunities in adopting personalized photoprotection strategies, aiming to promote skin health and prevent the harmful effects of UV radiation in the era of precision medicine.

The topical application of different galenic formulations can alter the thermographic images of skin: Limitations for public thermal screening on infection control situations.

BACKGROUND: To analyze whether the application of topical formulas as cosmetics or sunscreens could affect the skin thermographic readings in terms of infection control in pandemic situations. METHODS: The temperature of the skin of the dorsal region of the back and the face of 20 volunteers was followed after the application of 6 different types of gels, sunscreens, and make-up under controlled temperature and humidity conditions. High-resolution thermographic images were analyzed to calculate the temperature of treated skin compared to skin free of topical products. RESULTS: The application of hydroalcoholic gel resulted in a mean drop of more than 2°C just after 1 minute followed by organic sunscreens until 1.7°C. Recovery was observed progressively until minute 9. Color make-up type formulas, rich in iron oxide as well as sunscreens with mineral filters had little or no effect on the skin thermal response. CONCLUSIONS: It is possible to alter the skin temperature almost immediately by using hydroalcoholic gels and sunscreen cosmetics. So, it is possible to produce false negative data in the readings of patients screened thermically.

Sun protection, progress, myths, and inconsistencies (a proposal for the democratization of ISO 24443).

The concept of modern human sun protection is no more than one hundred years, but real development of it, including protection against UVA + UVB radiation (and more recently also the IR and blue light), has been no more than 30 years. One fundamental issue while formulating sunscreens is the photostability of the UV filters, which is particularly feeble for the UVA. The gold standard for the determination of sunscreen UVA protection "in vitro" is ISO 24443:2021. Still, interlaboratory results are not as consistent as expected. The Technical Committee for Cosmetics (ISO TC 217) has tried to standardize the method with precise specifications for the materials and equipment used. In particular, the standardization of UV exposure sources based on Xe arc lamps. This fact requires expensive equipment out of the reach of many laboratories to achieve adequate temperature control on the samples. In this paper, it will be shown that, within the experimental error, satisfactory results were achieved with a cheap commercial LED source irradiating only in the UVA spectra. Evidence is presented to conclude that other more relevant factors must be considered as the main cause of uncertainties.

Photoprotective measures among adolescents stratified by region: An analysis utilizing the National College Health Assessment.

BACKGROUND/PURPOSE: Exposure to sunlight has been shown to cause pigmentary alterations, photoaging and photocarcinogenesis. Understanding photoprotective patterns in adolescent populations is beneficial to public health initiatives. We utilized data provided by the American College Health Association's National College Health Assessment to evaluate photoprotective behaviors among adolescent populations. METHODS: Behavioral questions related to photoprotection were analyzed from the American College Health Association (ACHA) National College Health Assessment (NCHA) (Version III). RESULTS: When comparing races, Black/African American respondents had the lowest association of practicing photoprotective behaviors in comparison to white respondents (p < .05). When comparing US geographic regions, the south had the lowest association of photoprotective measures (p < .05). LIMITATIONS: The response rate of each institution varied, although there was still a large quantity of respondents. Finally, we cannot discern the specific reasoning for adolescent populations not using sunscreen. CONCLUSION: These data identify demographics where efforts to enhance education on photoprotective behaviors, specifically among skin of color and southern population, to support public health initiatives.

Awareness of sun exposure risks and photoprotection for preventing pigmentary disorders in Asian populations: Survey results from three Asian countries and expert panel recommendations.

BACKGROUND: In this article, we review and discuss the photoprotection behavior of Asians based on the literature, along with a subanalysis of an original online survey, and make recommendations to optimize photoprotection for Asian populations to prevent photoaging and pigmentary disorders. METHODS: An international panel of eight dermatologists from Asia (China, Korea, Japan, Singapore, Indonesia, and Vietnam) met to discuss sunscreen photoprotection for Asian patients. Additionally, a subanalysis of an online survey by 3000 respondents from three Asian countries (China, Indonesia, and Japan) investigated general public awareness and attitudes to sun exposure. RESULTS: A pre-meeting survey of the eight experts from Asia showed key concerns of Asian patients consulting dermatologists are pigmentary disorders, especially actinic/senile lentigo, post-inflammatory hyperpigmentation, melasma, vitiligo, and Hori's nevus. The survey subanalysis of participants from China, Indonesia, and Japan with predominantly Fitzpatrick skin types (FST) II to IV revealed that they are particularly concerned about sun exposure causing photoaging and pigmentary disorders. Most of the respondents indicated they have limited knowledge on sunlight radiation and appropriate sunscreen protection factors. Only 22%, 13%, and 3% for China, Indonesia, and Japan, respectively, systematically use multiple protective measures (using sunscreen, avoiding midday sun, staying in the shade, wearing a hat, protective clothing, and sunglasses) when exposed to the sun. CONCLUSIONS: Further education is needed for Asian populations on the importance of comprehensive daily photoprotection, including broad-spectrum sunscreen, with high UVA and visible light protection, to reduce and prevent photoaging and pigmentary disorders.

An optimized methodology for the determination of multiclass organic ultraviolet sunscreens and metabolites in human milk through chromatographic and chemometric resolution.

Organic UV filters (UVFS) are used to mitigate the dermal effects associated with health risks from UV radiation, making them essential in personal care products. UVFS are frequently identified in environmental samples due to their high lipophilicity and persistence, underscoring the urgency of comprehensive assessments and regulatory measures aimed at safeguarding ecosystems and human health. The present study reports a multiclass analytical method for determining 16 UV sunscreens and metabolites in breast milk based on an ultrasound-assisted-dispersive liquid-liquid micro-extraction (UA-DLLME) with further chromatographic and chemometric resolution. The experimental conditions of the UA-DLLME were optimized through the implementation of the Design of Experiment tools. To model the responses, least-squares and artificial neural network methodologies were implemented. The optimal conditions were found by employing the desirability function. The samples were analyzed through reverse-phase liquid chromatographic separation, UV diode array, and fast-scanning fluorescence detection. The chromatographic analysis enabled the resolution of 16 analytes in a total time of 13.0 min. Multivariate curve resolution-alternating least-square (MCR-ALS) modelling was implemented to resolve analytes that were not fully resolved and to determine analytes that coeluted with endogenous components of the breast milk samples. An enrichment factor of 5-fold concentration was obtained with this methodology, reaching recoveries between 65 % and 105 % for 13 multiclass UV sunscreens and metabolites in breast milk samples with RSD % and REP % lower than 12 %.

Biotechnological Potential of Macroalgae during Seasonal Blooms for Sustainable Production of UV-Absorbing Compounds.

Marine macroalgae (seaweeds) are important primary global producers, with a wide distribution in oceans around the world from polar to tropical regions. Most of these species are exposed to variable environmental conditions, such as abiotic (e.g., light irradiance, temperature variations, nutrient availability, salinity levels) and biotic factors (e.g., grazing and pathogen exposure). As a result, macroalgae developed numerous important strategies to increase their adaptability, including synthesizing secondary metabolites, which have promising biotechnological applications, such as UV-absorbing Mycosporine-Like Amino Acid (MAAs). MAAs are small, water-soluble, UV-absorbing compounds that are commonly found in many marine organisms and are characterized by promising antioxidative, anti-inflammatory and photoprotective properties. However, the widespread use of MAAs by humans is often restricted by their limited bioavailability, limited success in heterologous expression systems, and low quantities recovered from the natural environment. In contrast, bloom-forming macroalgal species from all three major macroalgal clades (Chlorophyta, Phaeophyceae, and Rhodophyta) occasionally form algal blooms, resulting in a rapid increase in algal abundance and high biomass production. This review focuses on the bloom-forming species capable of producing pharmacologically important compounds, including MAAs, and the application of proteomics in facilitating macroalgal use in overcoming current environmental and biotechnological challenges.

Occurrence and ecological risk assessment of organic UV filters in coastal waters of the Iberian Peninsula.

This study aimed to assess the presence of 21 UVFs and metabolites in coastal regions of the Iberian Peninsula, to evaluate their environmental risk, and identify possible influential factors affecting their measured concentrations. Sampling was carried out in spring and summer to assess possible seasonal variations. UVFs were detected in 43 of the 46 sampling sites. Only 5 were found above LOD: BP4, OC, BP3 and metabolites BP1 and BP8. Samples collected in Mar Menor had the greatest variety of compounds per sample and the highest cumulative concentrations. The risk was characterized using Risk Quotients (RQ). BP1 showed a Low environmental Risk in 2 sites while for OC the RQ indicated a Moderate Risk in 22 points. The variables that contribute most to the variation are population density, sampling season, whether it was an open bay or not, and level of urbanization. The presence of WWTPs had a lower influence.

Sun protection behaviors among children aged 6-18 years old, the role of socioeconomic factors: A cross-sectional study.

Background and Aims: Evaluation of sun protection behavior and related factors in children aged between 6 and 18 years in Isfahan, Iran. Methods: This cross-sectional study was conducted at outpatient pediatric clinics affiliated with Isfahan University of Medical Sciences, Isfahan, Iran during the summer of 2021. A checklist was designed, and the interviewer used that to gather the required information including children's demographic characteristics, families' socioeconomic data, and sun-protective behaviors in children. Results: The mean ± standard deviation (SD) age of children was 10.54 ± 3.61. Among the study population, 63.7% of children were male. The most common skin phototypes were II and III (33.5% each). 83.8% of children used at least one method of sun protection (94.5% of girls, 77.6% of boys, p < 0.001). Wearing long-sleeved clothes was the most frequent UV-protection method (48%), while sunscreen application was the least prevalent method (28.1%). Sun protection behaviors were more frequent among urban children (86.7%, p = 0.009) and children with wealthy families (94%, p = 0.035). Sun protection methods were used by most of the children whose mothers applied sunscreen on a daily basis (90.2%, p = 0.002) and all of the children whose mothers held a master's degree or above (100%, p = 0.004). Conclusion: Children's sun protection behavior is directly associated with demographic characteristics, families' socioeconomic level and maternal usage of sun protection measures. It is necessary to provide information and education about sun protection methods and the risks of excessive sun exposure to families and children, as well as facilitate their access to these.

Effects of TiO2 ultraviolet filter and sunscreens on coastal dune plant performance and competitive interactions.

Ultraviolet filters (UVFs) added to sunscreens (SS) are emerging contaminants in marine environments due to their adverse effects on organisms and ecosystems. UVFs have also been detected in beach-dune systems, but their influence on resident organisms has not been explored yet. Native plants are fundamental components of coastal dunes, and these ecologically/economically important systems are currently among the most threatened globally. Thus, understanding whether UVFs may act as threats to dune plants is crucial. This field study evaluated and compared the effects of titanium dioxide nanoparticles (nTiO2), one of the inorganic UVFs most commonly added to sunscreens, and those of a commercial sunscreen product containing it (SS-nTiO2) on the performance of adult dune plants of a native (Thinopyrum junceum) and a non-native invasive species (Carpobrotus sp. pl.) and their competitive interactions at environmentally realistic concentrations. The effects of nTiO2, SS-nTiO2 and of a sunscreen product containing just organic UVFs (SS-OF) on early life stages of T. junceum were also examined. Ti bulk content in sand and plants at the study site ranged from 970 to 1069 mg kg-1 and from 2 to 7.9 mg kg-1, respectively. Thinopyrum junceum adult plants periodically exposed during the summer season to seawater contaminated by SS-nTiO2 produced less biomass than un-exposed plants and nTiO2 exposed plants. nTiO2 and SS-nTiO2 reduced the capacity of T. junceum to control the spread of Carpobrotus. Both SS-nTiO2 and SS-OF reduced seedling emergence in T. junceum whereas nTiO2 did not. These results demonstrated that the periodical exposures of native dune plants to sunscreens could reduce their establishment success and growth and favor invasive plant spread potentially resulting in community structure changes. They also emphasize the need to assess the phytotoxicity not only of single UVFs but especially that of complete sunscreen products to design more eco-friendly formulations in the future.

Recent developments in tuning the efficacy of different types of sunscreens.

Due to recent global warming threats, the changes in the atmosphere have caused significant ultraviolet (UV) radiation exposure, primarily emitted by the sun, which creates more awareness of photoprotection. Sunscreen development has been a convenient and crucial approach to photoprotection against ultraviolet radiation. Due to high demand, upgrading the quality of sunscreen products and certifying methods are necessary to guarantee the safety of commercial sunscreen products for use. Sunscreen products should have a satisfactory amount of sun protection factor (SPF), ultraviolet A protection factor, as well as the photostability of the sunscreens for them to be considered effective and safe for use. A rigorous study on the effectiveness of the sunscreen components and their safety standards is essential for the productive use and further improvement of the available sunscreen materials. This article summarizes the effects and issues, protective measures of sunscreen usage, and its components, mainly ultraviolet filters.

Ruellia angustiflora (Nees) Lindau ex Rambo: extraction and characterization of phenolic compounds and evaluation of antiradical, photoprotective and antimicrobial activities.

Ruellia angustiflora is a shrub popularly known as flower of fire, used in traditional medicine as a healing agent. This study aims to verify the presence of characteristics of pharmaceutical interest in extracts from the root, stem and leaves of this species. The ideal time for ultrasound-assisted extraction is 60 min with a solid-liquid ratio of 1% (w/v). The kinetics of the reaction of the extracts with DPPH is biphasic, and IC50 values are related to the total phenolic compounds. Five phenolic compounds were identified in the extracts, where ferulic acid, rutin and quercetin showed to be the main responsible for the antiradical activity. The extracts displayed considerable photoprotective activity, mainly Ra-LE (SPF = 23). Ra-RE showed an inhibition halo similar to erythromycin against Streptococcus pyogenes. Taken together, these data reveal that Ruellia angustiflora is a source of phenolic compounds and has relevant antiradical, photoprotective and antibacterial activities.

Skin Cancer Prevention across the G7, Australia and New Zealand: A Review of Legislation and Guidelines.

Incidence rates of melanoma and keratinocyte skin cancers have been on the rise globally in recent decades. While there has been a select focus on personal sun protection awareness, to our knowledge, there is a paucity of legislation in place to help support citizens' efforts to protect themselves from the harmful effects of ultraviolet radiation (UVR). Given this, we conducted a comprehensive review of legislation and guidelines pertaining to a variety of sun protection-related topics in countries of the Group of Seven (G7), Australia and New Zealand. Australia was the only country to have banned tanning beds for individuals of all ages, while other select countries have instituted bans for minors. In workplace policy, there is very little recognition of the danger of occupational UVR exposure in outdoor workers, and thus very few protective measures are in place. With regard to sports and recreation, certain dermatological/professional associations have put forward recommendations, but no legislation was brought forward by government bodies outside of Australia and New Zealand. With regard to youth, while there are various guidelines and frameworks in place across several countries, adherence remains difficult in the absence of concrete legislation and standardization of procedures. Finally, only Australia and a few select jurisdictions in the United States have implemented sales tax exemptions for sunscreen products. In light of our findings, we have made several recommendations, which we anticipate will help reduce the rates of melanoma and keratinocyte cancers in years to come. However, minimizing UVR exposure is not without risk, and we, therefore, suggest the promotion of vitamin D supplementation in conjunction with sun protective practices to limit potential harm.

Toxicity assessment of binary mixtures of BP3 with 4-MBC (UV-filters), and BP3 with DEET (insect repellent) using the aquatic midge Chironomus riparius.

Personal care products have various organic ultraviolet filters (UV filters) in their composition to increase protection against ultraviolet radiation. Some of these products also contain insect repellents in their formulations. Consequently, these compounds reach freshwater ecosystems, exposing aquatic organisms to a cocktail of anthropogenic contaminants. In this study, the joint effects of two most frequently detected UV filters (Benzophenone - 3 (BP3) and Enzacamene (4-MBC)) and joint effects of BP3 combined with an insect repellent (N, N diethyl-3-methylbenzamide - DEET) were evaluated using life-history traits of the aquatic midge Chironomus riparius such as emergence rate, time to emergence and imagoes body weight. The results showed synergistic effects between BP3 and 4-MBC for C. riparius emergence rate. Regarding the effects of BP3 and DEET mixture, our analysis suggests synergism in the case of males but antagonism in the case of females' time to emergence. Our results imply that the effects of UV filters present in sediments within chemical mixtures are complex and that the evaluation of effects using different life-history traits can yield different patterns of responses. This study demonstrates the importance of assessing the combined effects of pollutants used/found concomitantly in aquatic systems for a more accurate risk assessment, as individual chemical testing can underestimate the toxicity of organic UV filters.