Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
Department of Applied Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad 500007, India.
J Med Chem. 2022 Feb 10;65(3):1822-1834. doi: 10.1021/acs.jmedchem.1c00750. Epub 2022 Jan 12.
Herein, we report three new metal-free, photochemically active single, dual, and combinatorial CORMs (photoCORMs) based on a carbazole-fused 1,3-dioxol-2-one moiety which released one equivalent of CO, two equivalent of CO, and a combination of one equivalent of each CO and anticancer drug upon one- and two-photon excitation, respectively. The photoCORMs exhibited good cellular uptake and real-time monitoring ability of CO uncaging by a color change approach in cancerous B16F10 cells. Interestingly, the cytotoxicity assay on B16F10 cells indicated that the dual photoCORM has increased anticancer activity over the single and combinatorial photoCORMs upon irradiation. Our results also showed that CO could accelerate the effectiveness of the well-known anticancer drug (chlorambucil). Finally, the evaluation of the dual photoCORM on an established murine melanoma tumor (C57BL/6J mouse model) manifested a significant regression of tumor volume and led to significant improvement (>50%) in the overall survivability.
在此，我们报道了三种基于咔唑稠合 1,3-二恶烷-2-酮部分的新型无金属、光化学活性的单、双和组合型一氧化碳释放分子（photoCORMs），它们分别在单光子和双光子激发下释放一个当量的 CO、两个当量的 CO，以及一个当量的 CO 和抗癌药物的组合。photoCORMs 在癌细胞 B16F10 中表现出良好的细胞摄取能力和通过颜色变化方法实时监测 CO 解笼的能力。有趣的是，对 B16F10 细胞的细胞毒性测定表明，双 photoCORM 在照射下比单和组合 photoCORM 具有更高的抗癌活性。我们的结果还表明，CO 可以加速著名抗癌药物（苯丁酸氮芥）的效果。最后，在已建立的鼠黑色素瘤肿瘤（C57BL/6J 小鼠模型）上对双 photoCORM 的评估表明肿瘤体积显著消退，并导致整体存活率显著提高（>50%）。
