Antiproliferative activity of diarylnaphthylpyrrolidine derivative via dual target inhibition

Verma Amit Kumar; Fatima Kaneez; Dudi Rajesh Kumar; Tabassum Misbah; Iqbal Hina; Kumar Yogesh; Luqman Suaib; Mondhe D. M.; Chanda Debabrata; Khan Feroz; Shanker Karuna; Negi Arvind S.

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Antiproliferative activity of diarylnaphthylpyrrolidine derivative via dual target inhibition

机译：双靶抑制的二芳基萘基吡咯烷衍生物的抗增殖活性

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Breast cancer is the second leading cause of deaths in women globally. Present communication deals with design and synthesis of a few diarylnaphthyls as possible anti-breast cancer agents. Among the thirty three representatives with significant antiproliferative activity compounds 23 and 50 were quite efficacious against human breast cancer cells. Compound 50 induced apoptosis in both MCF-7 and MDA-MB-231 cells and exerted S phase and G2/M phase arrest respectively via distinct mechanistic pathways. It showed moderate microtubule destabilization. Further, it exhibited DNA topoisomerase-II inhibition effect in MCF-7 cells. It was well tolerable and found safe up to 300 mg/kg dose in Swiss albino mice. The dual action antiproliferative effect of compound 50 is quite interesting and warrants for future development. (C) 2019 Elsevier Masson SAS. All rights reserved.

机译：乳腺癌是全球妇女死亡的第二个主要原因。目前的沟通与一些二芳基碱基的设计和合成作为可能的抗乳腺癌药剂。在具有显着抗增殖活性的三十三个代表中，23和50的抗抗原性化合物对人乳腺癌细胞相当有效。化合物50分别通过不同的机械途径诱导MCF-7和MDA-MB-231细胞中的细胞凋亡，并分别施加S相和G2 / M相阻滞。它显示出中度微管稳定化。此外，它在MCF-7细胞中表现出DNA TOPOISOMERASE-II抑制作用。它是良好的耐受性，并且在瑞士白化小鼠中发现了300毫克/千克的剂量。化合物50的双重作用抗增殖效应是非常有趣的，并且未来发展的认股权证是非常有趣的。（c）2019年Elsevier Masson SAS。版权所有。

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《European Journal of Medicinal Chemistry: Chimie Therapeutique》 |2020年第1期|共18页
作者
Verma Amit Kumar; Fatima Kaneez; Dudi Rajesh Kumar; Tabassum Misbah; Iqbal Hina; Kumar Yogesh; Luqman Suaib; Mondhe D. M.; Chanda Debabrata; Khan Feroz; Shanker Karuna; Negi Arvind S.;
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CIMAP CSIR PO CIMAP Kukrail Picnic Spot Rd Lucknow 226015 Uttar Pradesh India;

CIMAP CSIR PO CIMAP Kukrail Picnic Spot Rd Lucknow 226015 Uttar Pradesh India;

IIIM CSIR Canal Rd Jammu 180001 India;

IIIM CSIR Canal Rd Jammu 180001 India;

CIMAP CSIR PO CIMAP Kukrail Picnic Spot Rd Lucknow 226015 Uttar Pradesh India;

CIMAP CSIR PO CIMAP Kukrail Picnic Spot Rd Lucknow 226015 Uttar Pradesh India;

CIMAP CSIR PO CIMAP Kukrail Picnic Spot Rd Lucknow 226015 Uttar Pradesh India;

Acad Sci &

Innovat Res AcSIR Ghaziabad 201002 Uttar Pradesh India;

CIMAP CSIR PO CIMAP Kukrail Picnic Spot Rd Lucknow 226015 Uttar Pradesh India;

CIMAP CSIR PO CIMAP Kukrail Picnic Spot Rd Lucknow 226015 Uttar Pradesh India;

CIMAP CSIR PO CIMAP Kukrail Picnic Spot Rd Lucknow 226015 Uttar Pradesh India;

CIMAP CSIR PO CIMAP Kukrail Picnic Spot Rd Lucknow 226015 Uttar Pradesh India;

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正文语种 eng
中图分类药学;
关键词
Breast cancer; Apoptosis; Microtubule destabilization; Topoisomerase; Molecular docking studies; Acute oral toxicity;

机译：乳腺癌;细胞凋亡;微管稳定化;拓扑异构酶;分子对接研究;急性口腔毒性;

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1. Antiproliferative activity of diarylnaphthylpyrrolidine derivative via dual target inhibition [J] . Verma Amit Kumar, Fatima Kaneez, Dudi Rajesh Kumar, European Journal of Medicinal Chemistry: Chimie Therapeutique . 2020,第1期

机译：双靶抑制的二芳基萘基吡咯烷衍生物的抗增殖活性
2. Synthesis and biological evaluation of novel quinolone derivatives dual targeting histone deacetylase and tubulin polymerization as antiproliferative agents [J] . Wang Xuan, Jiang Xiaoye, Sun Shiyou, RSC Advances . 2018,第30期

机译：新型喹啉衍生物双靶向组蛋白脱乙酰酶和小管蛋白聚合为抗增殖剂的合成及生物学评价
3. Synthesis and biological evaluation of novel quinolone derivatives dual targeting histone deacetylase and tubulin polymerization as antiproliferative agents [J] . Xuan Wang, Xiaoye Jiang, Shiyou Sun, RSC Advances . 2018,第30期

机译：新型喹诺酮衍生物双靶向组蛋白脱乙酰基酶和微管蛋白聚合作为抗增殖剂的合成及生物学评价
4. Synthesis and Antiproliferative activities of Novel 2-Phenylaminopyrimidine (PAP) Derivatives [C] . Sheng Chang International Conference on Materials and Products Manufacturing Technology . 2014

机译：新型2-苯基氨基嘧啶（PAP）衍生物的合成与抗增殖活性
5. Inhibition of Ape1's DNA repair activity as a target in cancer: Identification of novel small molecules that have translational potential for molecularly targeted cancer therapy [D] . Bapat, Aditi Ajit 2009

机译：抑制Ape1的DNA修复活性作为癌症靶标：鉴定具有翻译潜力的新型小分子，可用于分子靶向癌症治疗
6. Targeting Estrogen Receptor Sites in Human Breast Cancer Cell Line T47D With Copper Conjugates of Nonsteriodal Anti-inflammatory Drug Derivatives: Antiproliferative Activity of Ketoprofen Derivative and its Copper Complex [O] . Dilip Kumar Saha, Shreelekha Padhye, Subhash Padhye 1947

机译：靶向铜与非杀菌消炎药衍生物的铜缀合物在人乳腺癌细胞系T47D中靶向雌激素受体的位点：抗增殖活性酮洛芬衍生物及其铜配合物的合成
7. Targeting Estrogen Receptor Sites in Human Breast Cancer Cell Line T47D With Copper Conjugates of Nonsteriodal Anti-inflammatory Drug Derivatives: Antiproliferative Activity of Ketoprofen Derivative and its Copper Complex [O] . Saha, Dilip Kumar, Padhye, Shreelekha, Padhye, Subhash 2001

机译：靶向铜与非杀菌消炎药衍生物的铜缀合物在人乳腺癌细胞系T47D中靶向雌激素受体的位点：抗增殖活性酮洛芬衍生物及其铜配合物的合成

Antiproliferative activity of diarylnaphthylpyrrolidine derivative via dual target inhibition

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