Tumor suppressive activities of solvatochromic 3,3'-azadimethylene dinaphthospiropyran in colon cancer model.
Tumor suppressive activities of solvatochromic 3,3'-azadimethylene dinaphthospiropyran in colon cancer model.
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溶致变色3，3 '-氮杂二亚甲基二萘并螺吡喃在结肠癌模型中的肿瘤抑制活性。
DOI：
10.1111/cbdd.13785
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发表时间：
2021-03
影响因子：
3
通讯作者：
Awasthi V
中科院分区：
文献类型：
--
作者：
Lagisetty P;Eeda V;Yadav VR;Nimmo SL;Subramaniam D;Powell DR;Awasthi V
螺吡喃因其热致变色和光致变色特性而被广泛研究，但其生物治疗特性尚未得到充分探索。我们报告了一种新型 3,3'-氮杂二亚甲基二萘螺吡喃 11 的抗增殖特性。二苯并螺吡喃和二萘螺吡喃是通过简单而便捷的方法合成的，分别使用水杨醛和 2-羟基-1-萘醛与环酮的酸催化羟醛缩合。结合二维核磁共振和 X 射线晶体学研究的结构阐明，我们提供了它们形成的假定机制。化合物 11 显示出溶剂化变色现象，并根据 pH 值显示出不同的光谱特性。在酸性条件下，11 保持开放形式，而碱化后它又恢复到封闭形式。基于 H441、HCT-116、MiaPaCa-2 和 Panc-1 癌细胞系的体外抗增殖活性，11 种被提交进行进一步研究。它减少了 HCT116 菌落球的形成，并诱导了 caspase 级联反应，表明细胞凋亡。体外增殖试验也表明11的HCl和三氟乙酸盐更有效。用 11（5 μg/天，腹膜内注射，持续 3 周）治疗携带 HCT-116 异种移植物的小鼠，可抑制肿瘤生长 62%。总体而言，结果揭示了一系列结构复杂但相对容易合成的新分子，其中化合物 11 代表了抗癌开发的先导。
Spiropyrans have been extensively investigated because of their thermo- and photochromic characteristics, but their biotherapeutic properties have not been explored much. We report anti-proliferative properties of a novel 3,3′-azadimethylene dinaphthospiropyran 11. Dibenzospiropyrans and dinaphthospiropyrans were synthesized by a simple and expedient method using acid-catalyzed aldol condensation of salicylaldehyde and 2-hydroxy-1-naphthaldehyde, respectively, with cyclic ketones. Together with structural elucidation by 2D NMR and X-ray crystallography studies, we provide a putative mechanism for their formation. Compound 11 showed solvatochromism and exhibited altered spectral characteristics depending on the pH. In acidic conditions, 11 remains in open form, whereas upon alkalinization it reverts back to closed form. Based on the in vitro anti-proliferative activity in H441, HCT-116, MiaPaCa-2, and Panc-1 cancer cell lines, 11 was submitted to further investigation. It reduced HCT116 colonosphere formation and demonstrated induction of caspase cascade, suggesting apoptosis. In vitro proliferation assays also suggested that HCl and trifluoroacetate salts of 11 are more effective. Treatment of mice carrying HCT-116 xenografts with 11 (5 μg/day, intraperitoneal for 3 weeks) suppressed tumor growth by 62%. Overall, the results reveal a new series of structurally complex, but relatively easy to synthesize molecules of which compound 11 represents a lead for anticancer development.
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影响因子：
2.9
作者：
Wojtyk, James T. C.;Wasey, Adnaan;Buncel, Erwin
通讯作者：
Buncel, Erwin
DOI：
10.1039/jr9330000430
发表时间：
1933-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY
影响因子：
--
作者：
Heilbron, IM;Heslop, RN;Irving, F
通讯作者：
Irving, F
影响因子：
15
作者：
Tong, Rong;Hemmati, Houman D.;Langer, Robert;Kohane, Daniel S.
通讯作者：
Kohane, Daniel S.
影响因子：
2.2
作者：
LANDEGREN, U
通讯作者：
LANDEGREN, U
DOI：
10.1039/jr9270001699
发表时间：
1927-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY
影响因子：
--
作者：
Dickinsion, R;Heilbron, IM
通讯作者：
Heilbron, IM