1-Styryl-1,3-diketones in the synthesis of spiro[oxindole-3,2'-pyrrolidines] with notable anticancer activity.

IF 3.9 2区化学 Q2 CHEMISTRY, APPLIED

Molecular Diversity Pub Date : 2025-02-04 DOI:10.1007/s11030-024-11099-x

Nikolay S Zimnitskiy, Vladislav Y Korotaev, Maria V Ulitko, Vyacheslav Y Sosnovskikh

引用次数: 0

Abstract

A regio- and stereoselective method for the synthesis of spiro[indolin-3,2'-pyrrolidine]-2-ones based on the [3 + 2] cycloaddition of azomethine ylides, generated in situ from isatins and proteinogenic α-amino acids, and (E)-5-arylpent-4-ene-1,3-diones under reflux in methanol within 12 h in 28-91% yields has been developed. A number of representative examples of spiro[indolin-3,2'-pyrrolidine]-2-ones have been studied for cytotoxic activity against HeLa cervical cancer cell line and human dermal fibroblasts (HDF) by the MTT assay. Every investigated compound has shown cytotoxic activity against HeLa cells (IC₅₀ 0.24-38.43 μM), while some of them have also shown low cytotoxicity against HDF cells (IC₅₀ 100.08-7821.27 μM). A preliminary structure-activity relationship (SAR) correlations have been made.

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具有显著抗癌活性的螺[3,2'-吡咯烷]合成中的1-苯乙烯-1,3-二酮。

建立了一种区域选择性和立体选择性合成螺旋[吲哚-3,2'-吡咯烷]-2-酮的方法，该方法是基于[3 + 2]环加成的，由isatins和蛋白源性α-氨基酸原位生成的亚甲基酰基化合物和(E)-5-芳基戊-4-烯-1,3-二酮，在甲醇回流12 h内，收率为28-91%。用MTT法研究了螺[吲哚-3,2'-吡咯烷]-2- 1对HeLa宫颈癌细胞系和人真皮成纤维细胞（HDF）的细胞毒活性。化合物对HeLa细胞的IC50均为0.24 ~ 38.43 μM，部分化合物对HDF细胞的IC50为100.08 ~ 7821.27 μM，具有较低的细胞毒性。初步建立了构效关系（SAR）。

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;