Laboratory of Organic Synthesis and Medicinal Chemistry (LaSOM), Núcleo de Ciências Exatas (NCEx), Campus Arapiraca, Federal University of Alagoas, CEP 57.309-005, Arapiraca, Alagoas, Brazil.
Laboratory of Organic Synthesis and Medicinal Chemistry (LaSOM), Núcleo de Ciências Exatas (NCEx), Campus Arapiraca, Federal University of Alagoas, CEP 57.309-005, Arapiraca, Alagoas, Brazil.
Chem Biol Interact. 2018 Aug 1;291:55-64. doi: 10.1016/j.cbi.2018.06.007. Epub 2018 Jun 11.
Naphthoquinone derivatives have various pharmacological properties. Here, we describe the synthesis of new 1,4-naphthoquinone derivatives inspired by lawsone and β-lapachone and their effects on both migration of fibroblasts in vitro and dermal wound healing in diabetic mice. NMR and FTIR spectroscopy aided characterization of chemical composition and demonstrated the molecular variations after the synthesis of four different derivatives, namely 2-bromo-1,4-naphthoquinone (termed derivative S3), 2-N-phenylamino-1,4-naphthoquinone (derivative S5), 2-N-isonicotinoyl-hydrazide-1,4-naphthoquinone (derivative S6), and 1-N-isonicotinoyl-hydrazone-[2-hydroxy-3-(3-methyl-2-butenyl)]-1,4-naphthoquinone (derivative S7). Our results indicate that derivatives S3, S5, S6 and S7 were non-toxic to the 3T3 fibroblast cell line. In scratch assays, derivatives S3 and S6, but not S5 or S7, stimulated the migration of fibroblasts. Compared with untreated diabetic mice, S3, S6 and S7 treatments accelerated wound closure. However, derivative S3 was optimal for the stimulation of epithelization, thereby increasing the number of keratinocyte layers and blood vessels, and reducing diffuse cellular infiltration, compared to derivatives S6 and S7. Our results suggest that novel 1,4-naphthoquinone derivatives promote fibroblast migration and accelerate wound closure under diabetic conditions.
萘醌衍生物具有多种药理学特性。在这里，我们描述了受lawsone 和 β-拉帕醌启发而合成的新型 1,4-萘醌衍生物，以及它们对体外成纤维细胞迁移和糖尿病小鼠皮肤伤口愈合的影响。NMR 和 FTIR 光谱辅助了化学成分的表征，并在合成了四种不同的衍生物后，即 2-溴-1,4-萘醌（称为衍生物 S3）、2-N-苯氨基-1,4-萘醌（衍生物 S5）、2-N-异烟酰基酰肼-1,4-萘醌（衍生物 S6）和 1-N-异烟酰基腙-[2-羟基-3-（3-甲基-2-丁烯基）]-1,4-萘醌（衍生物 S7），证明了分子的变化。我们的结果表明，衍生物 S3、S5、S6 和 S7 对 3T3 成纤维细胞系没有毒性。在划痕实验中，衍生物 S3 和 S6，但不是 S5 或 S7，刺激了成纤维细胞的迁移。与未处理的糖尿病小鼠相比，S3、S6 和 S7 处理加速了伤口闭合。然而，与 S6 和 S7 相比，衍生物 S3 更能刺激上皮化，从而增加角蛋白细胞层和血管的数量，并减少弥漫性细胞浸润。我们的结果表明，新型 1,4-萘醌衍生物在糖尿病条件下促进成纤维细胞迁移并加速伤口闭合。
