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Hyperpigmentation disorders may result from inappropriate melanin deposition and/or excessive melanin synthesis. They are classified mainly as aesthetic problems, but they can significantly affect human health by decreasing self-esteem. There are available only limited treatment options for hyperpigmentation disorder, among others, cosmetic products applied topically. Depigmenting ingredients were found to be ineffective and characterized by various side effects. As a result, many efforts are made to discover novel, potent, and safe melanogenesis inhibitors for possible use in topical cosmetic depigmenting formulations. Cinnamic acid derivatives constitute a widely tested group for that purpose. This article reports research in the group of N-alkyl cinnamamide derivatives (un)substituted in phenyl ring. Among tested series, (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide (compound 21) showed the most promising inhibitory properties in mushroom tyrosinase assay (IC 50  = 36.98 ± 1.07 µM for monophenolase activity, IC 50  = 146.71 ± 16.82 µM for diphenolase activity) and melanin production inhibition in B16F10 mouse melanoma cell line at concentration 6.25 µM resulting probably from decreasing of Tyr, Mitf, Tyrp-1, and Tyrp-2 genes expression. This compound also showed melanin production inhibitory properties in pigmented reconstructed human epidermis when used in 1 % and 2 % solutions in 50 % PEG400. In vitro evaluation of its safety profile showed no cytotoxicity to human keratinocytes HaCaT, human skin fibroblasts BJ, and human primary epidermal melanocytes HEMa, no mutagenicity in the Ames test, no genotoxicity in micronucleus test, no phototoxicity, as well as no skin irritation potential tested in PEG400 solution. This compound was also shown to penetrate across the epidermis to reach the possible site of action. The performed research led to classify (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide as a novel potential depigmenting cosmetic ingredient., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Chalcone is an important scaffold within medicinal and cosmetic chemistry. The structure enables multiple modifications which may result in obtaining compounds with desirable bioactivity. One of the chalcone derivatives, 4-methoxychalcone is a known cosmetic ingredient indexed in Cosing database as an antioxidant, bleaching, and skin conditioning substance. We investigated its in silico and in vitro safety profile. In silico study using Derek Nexus showed its potential of skin sensitisation, equivocal nature of chromosome damage in vitro in mammals, but also no mutagenic properties. In vitro research proved its activity as melanogenesis inhibitor in B16F10 cell line at the doses 12.5-3.125 μM. Evaluations performed in various cell lines showed that the cytotoxic doses were 50-25 μM. Tests in Episkin™ proved its ability to penetrate across epidermis and enabled classification of 2% formulation in PEG as non-irritant. In micronucleus tests it showed no genotoxicity. Studies in Cunninghamella echinulata model proved that 4-methoxychalcone was metabolised to less lipophilic products. 4-methoxychalcone showed phototoxic potential, its EC 50 (+UV) = 3.57 μg/mL, PIF = 10.19 and MPE = 0.428 were comparable to chlorpromazine. Moreover, 4-methoxychalcone showed ecotoxic potential in Microtox® assay with EC 50 (5 min) = 0.0047 mg/L and EC 50 (15 min) = 0.0033 mg/L. Although active doses were lower than toxic ones, some potential safety risks were noticed. Especially, due to the phototoxicity potential of 4-methoxychalcone, its use as depigmenting agent should involve avoidance of sunlight and use of appropriate photoprotection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cinnamic acid derivatives are widely used in cosmetics and possess various functions. This group of compounds includes both naturally occurring and synthetic substances. On the basis of the Cosmetic Ingredient Database (CosIng) and available literature, this review summarizes their functions in cosmetics, including their physicochemical and biological properties as well as reported adverse effects. A perfuming function is typical of many derivatives of cinnamaldehyde, cinnamyl alcohol, dihydrocinnamyl alcohol and cinnamic acid itself; these substances are commonly used in cosmetics all over the world. Some of them show allergic and photoallergic potential, resulting in restrictions in maximum concentrations and/or a requirement to indicate the presence of some substances in the list of ingredients when their concentrations exceed certain fixed values in a cosmetic product. Another important function of cinnamic acid derivatives in cosmetics is UV protection. Ester derivatives such as ethylhexyl methoxycinnamate (octinoxate), isoamyl p-methoxycinnamte (amiloxiate), octocrylene and cinoxate are used in cosmetics all over the world as UV filters. However, their maximum concentrations in cosmetic products are restricted due to their adverse effects, which include contact and a photocontact allergies, phototoxic contact dermatitis, contact dermatitis, estrogenic modulation and generation of reactive oxygen species. Other rarely utilized functions of cinnamic acid derivatives are as an antioxidant, in skin conditioning, hair conditioning, as a tonic and in antimicrobial activities. Moreover, some currently investigated natural and synthetic derivatives of cinnamic acid have shown skin lightening and anti-ageing properties. Some of them may become new cosmetic ingredients in the future. In particular, 4-hydroxycinnamic acid, which is currently indexed as a skin-conditioning cosmetics ingredient, has been widely tested in vitro and in vivo as a new drug candidate for the treatment of hyperpigmentation., (© 2018 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)