粉刺痤疮是一种涉及Cutibacterium acnes感染，炎症和过度角化的复杂皮肤疾病。我们评估了视黄醇6- [3-（金刚烷基）-4-羟基苯基] -2-萘甲酸（CD437）和其他16个视黄醇类似物作为潜在的抗C. acnes化合物的活性，并发现CD437表现出最高的抗微生物活性，其在C. acnes（ATCC6919和HM-513）的最低抑菌浓度为1μg / mL。与常用于治疗痤疮的视黄醇阿达帕林（最高64μg / mL）和四环素（最高16μg / mL）相比，CD437表现出2μg / mL的MBC。膜渗透试验表明，将C. acnes ATCC6919暴露在CD437上会损坏C. acnes ATCC6919细菌膜的完整性，此发现已通过扫描电子显微镜进行确认。此外，CD437下调了C. acnes ATCC6919毒力因子的表达，包括编码Christie-Atkins-Munch-Petersen因子1（CAMP1）、CAMP2、甘油酯酶B（GehB）、唾液酸酶B和神经氨酸酶的基因。在C。 acnes ATCC6919的小鼠皮肤感染模型中，CD437的局部治疗改善了皮肤病变，并在原位减少了细菌负担（P <0.001）。在人类NHEK原代细胞中，CD437降低了炎性细胞因子（白细胞介素-1α，约10倍；白细胞介素-6，约20倍；白细胞介素-8，约30倍；和肿瘤坏死因子-α，约6倍）的转录水平，并下调了KRT10（约10倍）、FLG（约4倍）和TGM1的转录水平（约2倍），表明CD437可以减轻炎症和过度角化。总之，CD437应该进一步受到关注，因为它具有潜在的双重功能，既可以作用于病原体，也可以作用于宿主，是一种潜在的痤疮治疗药物。

Acne vulgaris is a complex skin disease involving infection by Cutibacterium acnes, inflammation, and hyperkeratinization. We evaluated the activity of the retinoid 6-[3-(adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and 16 other retinoid analogs as potential anti-C. acnes compounds and found that CD437 displayed the highest antimicrobial activity with an MIC against C. acnes (ATCC 6919 and HM-513) of 1 μg/mL. CD437 demonstrated an MBC of 2 μg/mL compared to up to 64 μg/mL for the retinoid adapalene and up to 16 μg/mL for tetracycline, which are commonly used clinically to treat acne. Membrane permeability assays demonstrated that exposure of C. acnes ATCC 6919 to CD437 damaged the integrity of C. acnes ATCC 6919 bacterial membranes, and this finding was confirmed with scanning electron microscopy. Additionally, CD437 downregulated the expression of C. acnes ATCC 6919 virulence factors, including the genes encoding Christie-Atkins-Munch-Petersen factor 1 (CAMP1), CAMP2, glycerol-ester hydrolase B (GehB), sialidase B, and neuraminidase. In a mouse skin infection model of C. acnes ATCC 6919, topical treatment with CD437 ameliorated skin lesions and reduced the bacterial burden in situ (P < 0.001). In human NHEK primary cells, CD437 reduced the transcriptional levels of the coding genes for inflammatory cytokines (interleukin-1α, ~10-fold; interleukin-6, ~20-fold; interleukin-8, ~30-fold; and tumor necrosis factor-alpha, ~6-fold) and downregulated the transcriptional levels of KRT10 (~10-fold), FLG (~4-fold), and TGM1 (~2-fold), indicating that CD437 can diminish inflammation and hyperkeratinization. In summary, CD437 deserves further attention for its dual function as a potential acne therapeutic that potentially acts on both the pathogen and the host.