光药理学是一个年轻且快速发展的研究领域，为靶向治疗的新见解提供了巨大的潜力。虽然它主要专注于癌症治疗，但它也为其他疾病带来了希望。光药理学制剂的关键特征是同一分子中存在光敏和生物活性成分。在我们目前的研究中，我们合成了一种基于螺吡喃的亚稳态光酸，其中含有β-雌二醇的片段。由于其自质子化形式在溶液中的初始稳定性，该化合物在可见光照射下表现出负光致变色和光控荧光。我们对 HeLa 细胞模型进行了全面的生物学研究，以评估光酸的短期和长期细胞毒性、其代谢效应、其对信号传导和上皮间质转化超级系统途径的影响，以及富含光酸的细胞群比例癌症干细胞。我们的研究结果表明，这种衍生物对 HeLa 细胞具有较低的细胞毒性，但它能够显着减少富含癌症干细胞的恶性细胞侧群。此外，与β-雌二醇相比，适当的结构修饰会导致一些其他生物效应的增加。特别是，我们的物质具有罕见的 AP-1 抑制特性，并表现出一些促氧化和代谢作用，这些作用可以通过可见光照射进行调节。因此，新的基于雌二醇的光酸可能被认为是下一代抗癌研究中一种有前途的多效光药理学制剂

Photopharmacology is a young and rapidly developing field of research that offers significant potential for new insights into targeted therapy. While it primarily focuses on cancer treatment, it also holds promise for other diseases. The key feature of photopharmacological agents is the presence of a photosensitive and biologically active component in the same molecule. In our current study, we synthesized a spiropyran-based meta-stable state photoacid containing a fragment of β-estradiol. This compound exhibits negative photochromism and photocontrolled fluorescence under visible-light irradiation due to the initial stabilization of its self-protonated form in solution. We conducted comprehensive biological studies on the HeLa cells model to assess the short- and long-term cytotoxicity of the photoacid, its metabolic effects, its influence on signaling and epithelial-mesenchymal transition super-system pathways, and the proportion of the population enriched with cancer stem cells. Our findings reveal that this derivative demonstrates low cytotoxicity to HeLa cells, yet it is capable of dramatically reducing malignant cells side population enriched in cancer stem cells. Additionally, appropriate structural modification lead to an increase in some other biological effects compared to β-estradiol. In particular, our substance possesses rare properties of AP-1 suppression and demonstrates some pro-oxidant and metabolic effects, which can be regulated by visible light irradiation. As a result, the new estradiol-based photoacid may be considered a promising multi-acting photopharmacological agent for the next-generation anti-cancer research & development.Copyright © 2023. Published by Elsevier B.V.