Development of tumor-targeting aza-vesamicol derivatives with high affinity for sigma receptors for cancer theranostics
Development of tumor-targeting aza-vesamicol derivatives with high affinity for sigma receptors for cancer theranostics
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开发对 Sigma 受体具有高亲和力的肿瘤靶向 aza-vesamicol 衍生物，用于癌症治疗学
DOI：
10.1039/d2md00099g
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发表时间：
2022
影响因子：
4.1
通讯作者：
Ogawa Kazuma
中科院分区：
文献类型：
--
作者：
Mishiro Kenji;Wang Mengfei;Hirata Saki;Fuchigami Takeshi;Shiba Kazuhiro;Kinuya Seigo;Ogawa Kazuma
由于σ受体在各种癌细胞上高度表达，放射性标记的σ受体配体已被开发为癌症的成像和治疗探针。之前，我们合成并评估了放射性碘标记的vesamicol衍生物2-（4-[125 I]（4-碘苯基）哌啶）环己醇（（+）-[125 I]pIV）和放射性碘标记的氮杂-vesamicol衍生物反式-2-（4-（3-[125 I]（4-碘苯基）丙基）哌嗪-1-基）环己烷-1-醇（[125 I]2）作为sigma-1受体靶向探针。为了获得具有上级生物分布特性的sigma受体靶向探针，我们首先合成了12个含溴的氮杂-vesamicol衍生物，并评价了它们对sigma受体的亲和力。一种此类衍生物对sigma-1受体表现出高选择性，另一种衍生物对sigma-1和sigma-2受体表现出高亲和力。因此，制备了它们的卤素取代的含碘和放射性碘的化合物。与先前开发和评价的两种125 I标记的σ受体靶向探针[125 I]pIV和[125 I]2相比，125 I标记的化合物在肿瘤中表现出高摄取，在非靶组织中表现出较低摄取。因此，这些新的放射性碘标记的化合物应该是有前途的σ受体靶向探针。
As sigma receptors are highly expressed on various cancer cells, radiolabeled sigma receptor ligands have been developed as imaging and therapeutic probes for cancer. Previously, we synthesized and evaluated a radioiodinated vesamicol derivative, 2-(4-[125I](4-iodophenyl)piperidine)cyclohexanol ((+)-[125I]pIV), and a radioiodinated aza-vesamicol derivative, trans-2-(4-(3-[125I](4-iodophenyl)propyl)piperazin-1-yl)cyclohexan-1-ol ([125I]2), as sigma-1 receptor-targeting probes. In order to obtain sigma receptor-targeting probes with superior biodistribution characteristics, we firstly synthesized twelve bromine-containing aza-vesamicol derivatives and evaluated their affinity for sigma receptors. One such derivative exhibited high selectivity for the sigma-1 receptor and another exhibited high affinity for both the sigma-1 and sigma-2 receptors. Thus, their halogen-substituted iodine- and radioiodine-containing compounds were prepared. The 125I-labeled compounds exhibited high uptake in tumor and lower uptake in non-target tissues than the two previously developed and evaluated 125I-labeled sigma receptor-targeting probes, [125I]pIV and [125I]2. Therefore, these novel radioiodine-labeled compounds should be promising as sigma receptor-targeting probes.