Self-Assembled Alkylated Polyamine Analogs as Supramolecular Anticancer Agents.
Self-Assembled Alkylated Polyamine Analogs as Supramolecular Anticancer Agents.
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DOI：
10.3390/molecules27082441
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发表时间：
2022-04-10
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影响因子：
--
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构象受限的多胺类似物PG 11047是一种众所周知的候选药物，其在广谱癌症中调节多胺代谢并抑制癌细胞生长。在这里，我们报告的PG11047类似物（HPGs）含有不同长度的烷基链的构效关系研究，同时保持不饱和精胺骨架不变。更高对称同系物的合成是通过比先前的PG 11047合成路线步骤更少的合成路线实现的。两亲性HPG类似物进行自组装并形成球形纳米颗粒，其尺寸随着疏水烷基链长的增加而增加。体外抗癌活性的评估显示，与PG 11047相比，具有较长烷基链的类似物在人结肠癌细胞系HCT 116中的癌细胞抑制活性增加超过8倍，并且在人肺癌细胞系A549中增加超过10倍。精胺氧化酶（SMOX）的抑制评价显示，PG 11047没有活性，但活性观察到其更高的对称同系物。与参比SMOX抑制剂MDL72527相比，表现最好的HPG类似物的活性好9倍。
Conformationally restrained polyamine analog PG11047 is a well-known drug candidate that modulates polyamine metabolism and inhibits cancer cell growth in a broad spectrum of cancers. Here, we report a structure–activity relationship study of the PG11047 analogs (HPGs) containing alkyl chains of varying length, while keeping the unsaturated spermine backbone unchanged. Synthesis of higher symmetrical homologues was achieved through a synthetic route with fewer steps than the previous route to PG11047. The amphiphilic HPG analogs underwent self-assembly and formed spherically shaped nanoparticles whose size increased with the hydrophobic alkyl group’s increasing chain length. Assessment of the in vitro anticancer activity showed more than an eight-fold increase in the cancer cell inhibition activity of the analogs with longer alkyl chains compared to PG11047 in human colon cancer cell line HCT116, and a more than ten-fold increase in human lung cancer cell line A549. Evaluation of the inhibition of spermine oxidase (SMOX) showed no activity for PG11047, but activity was observed for its higher symmetrical homologues. Comparison with a reference SMOX inhibitor MDL72527 showed nine-fold better activity for the best performing HPG analog.
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影响因子：
7.3
作者：
Valasinas, A;Sarkar, A;Frydman, B
通讯作者：
Frydman, B
影响因子：
2
作者：
Dunston TT;Khomutov MA;Gabelli SB;Stewart TM;Foley JR;Kochetkov SN;Khomutov AR;Casero RA Jr
通讯作者：
Casero RA Jr
影响因子：
3.6
作者：
Huang, Y;Pledgie, A;Davidson, NE
通讯作者：
Davidson, NE
影响因子：
3.4
作者：
Streiff, RR;Bender, JF
通讯作者：
Bender, JF
影响因子：
4.9
作者：
Dong Y;Zhu Y;Li J;Zhou QH;Wu C;Oupický D
通讯作者：
Oupický D