Synthesis and biological evaluation of bisspirooxindole-hexahydroindolizines as potential anticancer agent.

IF 4.3 2区化学 Q2 CHEMISTRY, APPLIED

Molecular Diversity Pub Date : 2026-07-13 DOI:10.1007/s11030-026-11657-5

Fereshteh Ahmadi, Mohammad Javadi, Naeimeh Shahrestani, Roshan Baharinia, Yasaman Tamaddon-Abibigloo, Hooman Aghamirza Moghim Aliabadi, Amir Kashtiaray, Behrouz Notash

引用次数: 0

Abstract

In this study, we report an efficient three-component domino reaction of isatin, pipecolic acid, and alkyl 2-(1-methyl-2-oxoindolin-3-ylidene) acetate that provided a simple and convenient route to synthesis of novel methyl-2,2″-dioxo-1',5',6',7',8',8a'-hexahydrodispiro[indoline-3,2'-indolizine-3',3″-indoline]-1'-carboxylate derivatives. This regio- and diastereoselective transformation presumably proceeds through a domino sequence involving azomethine ylide formation followed by a [3 + 2] cycloaddition reaction, leading to the construction of the bisspirooxindole scaffold in a one-pot operation. Preliminary biological evaluation revealed that the synthesized compounds exhibited significant cytotoxic activity against MCF-7 breast cancer cells. The docking study suggested that compound 3d can act as an estrogen receptor alpha (ER-α) modulator, and can be considered a promising lead compound.

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潜在抗癌剂双螺环吲哚-六氢吲哚嗪的合成及生物学评价。

在这项研究中，我们报道了一种高效的三组分多米诺反应，由isatin， pipecolic酸和烷基2-（1-甲基-2-吲哚啉-3-吡啶）醋酸酯，为合成新的甲基-2,2″-二氧基-1',5',6',7',8',8a'-hexahydrodispiro[吲哚-3,2'-吲哚嗪-3‘，3″-吲哚啉]-1’-羧酸衍生物提供了简单方便的途径。这种区域选择性和非对映选择性转化可能是通过一个多米诺骨牌序列进行的，其中包括偶亚甲基酰基形成，然后是[3 + 2]环加成反应，导致双螺环吲哚支架在一锅操作中构建。初步生物学评价表明，合成的化合物对MCF-7乳腺癌细胞具有显著的细胞毒活性。对接研究表明，化合物3d可作为雌激素受体α (ER-α)调节剂，是一种很有前景的先导化合物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;