Institute of Organic Chemistry, Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany.
Institute of Biological and Chemical Systems-FMS, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany.
Int J Mol Sci. 2022 May 18;23(10):5657. doi: 10.3390/ijms23105657.
Antimitotic agents such as the clinically approved vinca alkaloids, taxanes and epothilone can arrest cell growth during interphase and are therefore among the most important drugs available for treating cancer. These agents suppress microtubule dynamics and thus interfere with intracellular transport, inhibit cell proliferation and promote cell death. Because these drugs target biological processes that are essential to all cells, they face an additional challenge when compared to most other drug classes. General toxicity can limit the applicable dose and therefore reduce therapeutic benefits. Photopharmacology aims to avoid these side-effects by introducing compounds that can be applied globally to cells in their inactive form, then be selectively induced to bioactivity in targeted cells or tissue during a defined time window. This review discusses photoswitchable analogues of antimitotic agents that have been developed by combining different photoswitchable motifs with microtubule-stabilizing or microtubule-destabilizing agents.
抗有丝分裂药物，如临床批准的长春花生物碱、紫杉烷类和埃坡霉素，可以在细胞间期阻止细胞生长，因此是治疗癌症最有效的药物之一。这些药物抑制微管动力学，从而干扰细胞内运输，抑制细胞增殖并促进细胞死亡。由于这些药物针对的是所有细胞都必需的生物过程，因此与大多数其他药物类别相比，它们面临着额外的挑战。一般毒性会限制适用剂量，从而降低治疗效果。光药理学旨在通过引入可以以非活性形式全局应用于细胞的化合物来避免这些副作用，然后在定义的时间窗口内选择性地诱导靶向细胞或组织中的生物活性。本综述讨论了通过将不同的光开关基序与微管稳定或微管破坏剂结合开发的抗有丝分裂药物的光开关类似物。
