Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Universita' degli Studi di Roma "La Sapienza", Via degli Apuli 9, I-00185, Roma, Italy.
Centre of Excellence on Neurodegenerative Diseases, Universita' degli Studi di Milano, Via Balzaretti, 9, I-20133, Milano, Italy.
Sci Rep. 2017 May 31;7(1):2510. doi: 10.1038/s41598-017-02820-y.
Estrogen deprivation is associated with delayed healing, while estrogen replacement therapy (ERT) accelerates acute wound healing and protects against development of chronic wounds. However, current estrogenic molecules have undesired systemic effects, thus the aim of our studies is to generate new molecules for topic administration that are devoid of systemic effects. Following a preliminary study, the new 17β-estradiol derivatives 1 were synthesized. The estrogenic activity of these novel compounds was evaluated in vitro using the cell line ERE-Luc B17 stably transfected with an ERE-Luc reporter. Among the 17β-estradiol derivatives synthesized, compounds 1e and 1f showed the highest transactivation potency and were therefore selected for the study of their systemic estrogenic activity. The study of these compounds in the ERE-Luc mouse model demonstrated that both compounds lack systemic effects when administered in the wound area. Furthermore, wound-healing experiments showed that 1e displays a significant regenerative and anti-inflammatory activity. It is therefore confirmed that this class of compounds are suitable for topical administration and have a clear beneficial effect on wound healing.
雌激素剥夺与愈合延迟有关，而雌激素替代疗法 (ERT) 可加速急性伤口愈合并防止慢性伤口的发展。然而，目前的雌激素分子具有不理想的全身作用，因此我们的研究旨在生成用于局部给药的新分子，这些新分子没有全身作用。在初步研究之后，我们合成了新的 17β-雌二醇衍生物 1。使用稳定转染 ERE-Luc 报告基因的 ERE-Luc B17 细胞系，体外评估这些新型化合物的雌激素活性。在所合成的 17β-雌二醇衍生物中，化合物 1e 和 1f 显示出最高的转录激活效力，因此被选择用于研究其全身雌激素活性。在 ERE-Luc 小鼠模型中的研究表明，当在伤口区域给药时，这两种化合物均没有全身作用。此外，伤口愈合实验表明 1e 具有显著的再生和抗炎活性。因此可以确认，这类化合物适合局部给药，并对伤口愈合有明显的有益作用。
