受 tacrolide 类化合物启发的亲电甾体的合成与生物学评价
Synthesis and Biological Evaluations of Electrophilic Steroids Inspired by the Taccalonolides.
作者信息
Clanton Nicholas A, Hastings Shayne D, Foultz Griffin B, Contreras Julie A, Yee Samantha S, Arman Hadi D, Risinger April L, Frantz Doug E
机构信息
Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas 78249, United States.
Department of Pharmacology and Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, United States.
出版信息
ACS Med Chem Lett. 2020 Nov 20;11(12):2534-2543. doi: 10.1021/acsmedchemlett.0c00534. eCollection 2020 Dec 10.
Abstract
Natural products have served as inspirational scaffolds for the design and synthesis of novel antineoplastic agents. Here we present our preliminary efforts on the synthesis and biological evaluation of a new class of electrophilic steroids inspired by the naturally occurring taccalonolides. We demonstrate that these simplified analogs exhibit highly persistent antiproliferative properties similar to the taccalonolides and retain activity against resistant cancer cell lines that warrants further preclinical development.
摘要
天然产物一直是设计和合成新型抗肿瘤药物的灵感来源。在此，我们展示了我们在合成和生物学评估一类受天然存在的塔克醇内酯启发的新型亲电甾体方面的初步努力。我们证明，这些简化的类似物表现出与塔克醇内酯相似的高度持久的抗增殖特性，并对耐药癌细胞系保持活性，这值得进一步进行临床前开发。
相似文献
1
Synthesis and Biological Evaluations of Electrophilic Steroids Inspired by the Taccalonolides.受 tacrolide 类化合物启发的亲电甾体的合成与生物学评价
ACS Med Chem Lett. 2020 Nov 20;11(12):2534-2543. doi: 10.1021/acsmedchemlett.0c00534. eCollection 2020 Dec 10.
2
Taccalonolides E and A: Plant-derived steroids with microtubule-stabilizing activity.他卡醇内酯E和A：具有微管稳定活性的植物源甾体。
Cancer Res. 2003 Jun 15;63(12):3211-20.
3
Identification and biological activities of new taccalonolide microtubule stabilizers.新型塔卡醇内酯微管稳定剂的鉴定与生物活性。
J Med Chem. 2011 Sep 8;54(17):6117-24. doi: 10.1021/jm200757g. Epub 2011 Aug 11.
4
Potent taccalonolides, AF and AJ, inform significant structure-activity relationships and tubulin as the binding site of these microtubule stabilizers.强效的塔卡隆内酯 AF 和 AJ，提供了重要的结构活性关系和微管作为这些微管稳定剂结合位点的信息。
J Am Chem Soc. 2011 Nov 30;133(47):19064-7. doi: 10.1021/ja209045k. Epub 2011 Nov 8.
5
Taccalonolide microtubule stabilizers.他卡醇内酯类微管稳定剂。
Bioorg Med Chem. 2014 Sep 15;22(18):5091-6. doi: 10.1016/j.bmc.2014.01.012. Epub 2014 Jan 15.
6
Taccalonolides: Structure, semi-synthesis, and biological activity.紫杉叶素内酯：结构、半合成及生物活性。
Front Pharmacol. 2022 Aug 11;13:968061. doi: 10.3389/fphar.2022.968061. eCollection 2022.
7
Taccalonolides: Novel microtubule stabilizers with clinical potential.塔卡隆内酯类：具有临床潜力的新型微管稳定剂。
Cancer Lett. 2010 May 1;291(1):14-9. doi: 10.1016/j.canlet.2009.09.020. Epub 2009 Oct 31.
8
Pharmacokinetic Analysis and in Vivo Antitumor Efficacy of Taccalonolides AF and AJ.他卡诺内酯AF和AJ的药代动力学分析及体内抗肿瘤疗效
J Nat Prod. 2017 Feb 24;80(2):409-414. doi: 10.1021/acs.jnatprod.6b00944. Epub 2017 Jan 23.
9
The taccalonolides: microtubule stabilizers that circumvent clinically relevant taxane resistance mechanisms.他卡缩醇内酯类：一类能规避临床上相关紫杉烷耐药机制的微管稳定剂。
Cancer Res. 2008 Nov 1;68(21):8881-8. doi: 10.1158/0008-5472.CAN-08-2037.
10
Taccalonolides: A Novel Class of Microtubule-Stabilizing Anticancer Agents.他卡缩醇内酯类：一类新型的微管稳定抗癌剂。
Cancers (Basel). 2021 Feb 22;13(4):920. doi: 10.3390/cancers13040920.
引用本文的文献
1
Recent Advances in Steroid Discovery: Structural Diversity and Bioactivity of Marine and Terrestrial Steroids.类固醇发现的最新进展：海洋和陆地类固醇的结构多样性与生物活性
Int J Mol Sci. 2025 Mar 30;26(7):3203. doi: 10.3390/ijms26073203.
本文引用的文献
1
Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019.天然产物：1981 年 1 月至 2019 年 9 月近四十年来的新药来源
J Nat Prod. 2020 Mar 27;83(3):770-803. doi: 10.1021/acs.jnatprod.9b01285. Epub 2020 Mar 12.
2
Elucidating target specificity of the taccalonolide covalent microtubule stabilizers employing a combinatorial chemical approach.采用组合化学方法阐明塔卡隆内酯共价微管稳定剂的靶标特异性。
Nat Commun. 2020 Jan 31;11(1):654. doi: 10.1038/s41467-019-14277-w.
3
Molecular docking, anti-proliferative activity and induction of apoptosis in human liver cancer cells treated with androstane derivatives: Implication of PI3K/AKT/mTOR pathway.利用雄激素衍生物对人肝癌细胞进行分子对接、抗增殖活性和诱导细胞凋亡作用及其对 PI3K/AKT/mTOR 通路的影响。
J Steroid Biochem Mol Biol. 2020 Apr;198:105604. doi: 10.1016/j.jsbmb.2020.105604. Epub 2020 Jan 23.
4
New Zampanolide Mimics: Design, Synthesis, and Antiproliferative Evaluation.新型扎那米林类似物的设计、合成与抗增殖活性评价。
Molecules. 2020 Jan 15;25(2):362. doi: 10.3390/molecules25020362.
5
Fulvestrant in the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: A review.氟维司群治疗激素受体阳性/人表皮生长因子受体 2 阴性晚期乳腺癌：综述。
Cancer Med. 2019 May;8(5):1943-1957. doi: 10.1002/cam4.2095. Epub 2019 Apr 19.
6
Crystal Structure of the Cyclostreptin-Tubulin Adduct: Implications for Tubulin Activation by Taxane-Site Ligands.环孢菌素-微管蛋白加合物的晶体结构：对紫杉烷结合位点配体激活微管蛋白的影响。
Int J Mol Sci. 2019 Mar 20;20(6):1392. doi: 10.3390/ijms20061392.
7
C-6α- vs C-7α-Substituted Steroidal Aromatase Inhibitors: Which Is Better? Synthesis, Biochemical Evaluation, Docking Studies, and Structure-Activity Relationships.C-6α-与 C-7α-取代甾体芳香酶抑制剂：哪个更好？合成、生化评价、对接研究和构效关系。
J Med Chem. 2019 Apr 11;62(7):3636-3657. doi: 10.1021/acs.jmedchem.9b00157. Epub 2019 Mar 26.
8
Naturally occurring aromatic steroids and their biological activities.天然存在的芳香甾体及其生物活性。
Appl Microbiol Biotechnol. 2018 Jun;102(11):4663-4674. doi: 10.1007/s00253-018-8968-7. Epub 2018 Apr 21.
9
Structure-based design of targeted covalent inhibitors.基于结构的靶向共价抑制剂设计。
Chem Soc Rev. 2018 Jun 5;47(11):3816-3830. doi: 10.1039/c7cs00220c.
10
Taccalonolide Microtubule Stabilizers Generated Using Semisynthesis Define the Effects of Mono Acyloxy Moieties at C-7 or C-15 and Disubstitutions at C-7 and C-25.使用半合成方法生成的塔卡醇内酯微管稳定剂定义了 C-7 或 C-15 的单烷氧基部分和 C-7 和 C-25 的双取代基的作用。
J Nat Prod. 2018 Mar 23;81(3):579-593. doi: 10.1021/acs.jnatprod.7b00967. Epub 2018 Jan 23.
Zotero 插件