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本文引用的文献

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Design, Synthesis, and Investigation of the Pharmacokinetics and Anticancer Activities of Indenoisoquinoline Derivatives That Stabilize the G-Quadruplex in the Promoter and Inhibit Topoisomerase I.设计、合成及吲哚异喹啉衍生物的药代动力学和抗癌活性研究，该衍生物能稳定启动子中的 G-四链体并抑制拓扑异构酶 I。
J Med Chem. 2024 May 9;67(9):7006-7032. doi: 10.1021/acs.jmedchem.3c02303. Epub 2024 Apr 26.
2
G-quadruplexes on chromosomal DNA negatively regulates topoisomerase 1 activity.染色体 DNA 上的 G-四链体负调控拓扑异构酶 1 的活性。
Nucleic Acids Res. 2024 Mar 21;52(5):2142-2156. doi: 10.1093/nar/gkae073.
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G-quadruplex ligands in cancer therapy: Progress, challenges, and clinical perspectives.癌症治疗中的G-四链体配体：进展、挑战与临床前景
Life Sci. 2024 Mar 1;340:122481. doi: 10.1016/j.lfs.2024.122481. Epub 2024 Jan 30.
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Synthesis of 3-sulfenylindole derivatives from 4-hydroxy-2H-chromene-2-thione and indole using oxidative cross-dehydrogenative coupling reaction and anti-proliferative activity study of some of their sulfone derivatives.从 4-羟基-2H-色烯-2-硫酮和吲哚出发，通过氧化交叉脱氢偶联反应合成 3-亚磺酰基吲哚衍生物及其一些砜衍生物的抗增殖活性研究。
Bioorg Chem. 2023 Dec;141:106900. doi: 10.1016/j.bioorg.2023.106900. Epub 2023 Oct 4.
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Dual Targeting Topoisomerase/G-Quadruplex Agents in Cancer Therapy-An Overview.癌症治疗中的双靶点拓扑异构酶/G-四链体药物——综述
Biomedicines. 2022 Nov 15;10(11):2932. doi: 10.3390/biomedicines10112932.
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New antiproliferative agents derived from tricyclic 3,4-dihydrobenzo[4,5]imidazo[1,2-a][1,3,5]triazine scaffold: Synthesis and pharmacological effects.新型三环 3,4-二氢苯并[4,5]咪唑并[1,2-a][1,3,5]三嗪骨架衍生的抗增殖剂：合成与药理作用。
Arch Pharm (Weinheim). 2022 Nov;355(11):e2200295. doi: 10.1002/ardp.202200295. Epub 2022 Jul 29.
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Anticancer Drugs Approved by the US Food and Drug Administration From 2009 to 2020 According to Their Mechanism of Action.2009 年至 2020 年美国食品和药物管理局批准的基于作用机制的抗癌药物。
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Targeting the KRAS oncogene: Synthesis, physicochemical and biological evaluation of novel G-Quadruplex DNA binders.靶向KRAS癌基因：新型G-四链体DNA结合剂的合成、理化性质及生物学评价
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9
Benzothiopyranoindole- and pyridothiopyranoindole-based antiproliferative agents targeting topoisomerases.苯并噻吩并吲哚和吡啶并噻吩并吲哚类拓扑异构酶靶向抗增殖剂。
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10
Common G-Quadruplex Binding Agents Found to Interact With i-Motif-Forming DNA: Unexpected Multi-Target-Directed Compounds.常见的G-四链体结合剂被发现可与形成i-基序的DNA相互作用：意外的多靶点导向化合物。
Front Chem. 2018 Jul 24;6:281. doi: 10.3389/fchem.2018.00281. eCollection 2018.

探索多靶点药理学：苯并硫代吡喃并吲哚类化合物作为G-四链体稳定剂和拓扑异构酶I抑制剂用于有效的抗癌策略。

Pursuing Polypharmacology: Benzothiopyranoindoles as G-Quadruplex Stabilizers and Topoisomerase I Inhibitors for Effective Anticancer Strategies.

作者信息

Salerno Silvia, Barresi Elisabetta, Roggia Michele, Natale Benito, Marzano Simona, Hyeraci Mariafrancesca, Reina Serena Concetta Rita, Baglini Emma, Amato Jussara, Salvati Erica, Dalla Via Lisa, Da Settimo Federico, Cosconati Sandro, Taliani Sabrina

机构信息

Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.

Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Lungarno Pacinotti 43/44, 56126, Pisa, Italy.

出版信息

ACS Med Chem Lett. 2024 Oct 2;15(11):1875-1883. doi: 10.1021/acsmedchemlett.4c00313. eCollection 2024 Nov 14.

DOI:10.1021/acsmedchemlett.4c00313
PMID:39563818
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11571019/
Abstract

Here, we explored the benzothiopyranoindole scaffold to develop antiproliferative agents with a polypharmacological profile targeting both G-quadruplex (G4)-structures and Topoisomerase (Topo) I enzyme. In a preliminary optimization phase, compound was selected from an in-house collection as a suitable lead for the rational development of a small library of analogs (-). When assayed in NIH's NCI-60 Human Cancer Cell Line In Vitro Screen Program, compound and its demethylated analogue showed significant antiproliferative/cytotoxic activity. Furthermore, results suggested for and a dual mechanism of action, effectively binding and stabilizing G4 structures, while inhibiting the relaxation activity of TopoI and II. Notably, these compounds displayed a certain selectivity toward TopoI. The polypharmacological profile of and was validated in a human colon carcinoma cell line, underscoring their potential as lead candidates for developing novel and efficacious anticancer agents.

摘要

在此，我们探索了苯并噻吩并吲哚支架，以开发具有多药理学特性的抗增殖剂，该特性靶向G-四链体（G4）结构和拓扑异构酶（Topo）I酶。在初步优化阶段，从内部化合物库中选择化合物 作为合理开发一小类类似物（-）的合适先导物。在国立卫生研究院的NCI-60人类癌细胞系体外筛选程序中进行测定时，化合物 和其去甲基化类似物 显示出显著的抗增殖/细胞毒性活性。此外，结果表明 和 具有双重作用机制，能有效结合并稳定G4结构，同时抑制TopoI和II的松弛活性。值得注意的是，这些化合物对TopoI表现出一定的选择性。 和 的多药理学特性在人结肠癌细胞系中得到验证，突出了它们作为开发新型有效抗癌药物的潜在先导候选物的潜力。