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基于间充质干细胞的新型吲哚和苯并咪唑并[1,2-c]喹唑啉在抗癌治疗中的应用潜力

Potential of Using New Indole- and Benzimidazo[1,2-C]quinazolines in Anticancer Therapy Based on Mesenchymal Stem Cells.

作者信息

Radzikowska-Bűchner Elżbieta, Radej Sebastian, Niezabitowska Ewa, Sitarz Robert, Szewc Monika

机构信息

Institute of Medical Sciences, The John Paul II Catholic University of Lublin, Lublin, Poland.

Radzikowska Clinic, Warszawa, Poland.

出版信息

Cancer Manag Res. 2025 Jun 11;17:1087-1097. doi: 10.2147/CMAR.S516593. eCollection 2025.

Abstract

PURPOSE

The study of the cytotoxic effect of variously substituted indole- and benzimidazo[1,2-c]quinazolines may prove particularly valuable in the context of developing new, effective anticancer therapies based on MSCs. The unique ability of MSCs to migrate and inhabit the tumor microenvironment makes them an ideal tool for transferring chemotherapeutic agents. The aim of this study was to evaluate the cytotoxic activity of 4-(6-indolo[1,2-c]quinazoline)2-methyl-benzene-1,3-diol (compound A) and 4-(6-benzimidazolo[1,2-c]quinazoline)2-methyl-benzene-1,3-diol (compound B) relative to the adipose-derived mesenchymal stem cells line (ASC52-telo) and the fibroblast line (HDFa).

MATERIALS AND METHODS

The test was performed on commercial cell lines: ASC52-telo and HDFa which were incubated with compounds A and B at four concentrations: 1 μg/mL, 2 μg/mL, 4 μg/mL, 8 μg/mL for 48 and 72 hours. The MTT test was performed to assess the cytotoxicity and determine the IC value of compounds A and B against both tested cell lines.

RESULTS

The results of the research indicate that both tested compounds showed stronger cytotoxic activity towards ASC52-telo than HDFa cells. In addition, compound A is characterized by greater cytotoxicity towards both tested cell lines compared to compound B.

CONCLUSION

The indole- and benzimidazo[1,2-c]quinazolines used in the study could potentially be used in MSCs-based therapy. There is a need to further investigate the safety of using MSCs as drug carriers, and to examine the anticancer activity of the tested compounds, as well as to perform additional and valuable assays, such as enzymatic and toxicity tests.

摘要

目的

在基于间充质干细胞(MSCs)开发新型有效抗癌疗法的背景下,研究各种取代的吲哚和苯并咪唑并[1,2 - c]喹唑啉的细胞毒性作用可能具有特别重要的价值。MSCs迁移并定位于肿瘤微环境的独特能力使其成为转运化疗药物的理想工具。本研究的目的是评估4 -(6 - 吲哚并[1,2 - c]喹唑啉)-2 - 甲基 - 苯 - 1,3 - 二醇(化合物A)和4 -(6 - 苯并咪唑并[1,2 - c]喹唑啉)-2 - 甲基 - 苯 - 1,3 - 二醇(化合物B)相对于脂肪来源的间充质干细胞系(ASC52 - telo)和成纤维细胞系(HDFa)的细胞毒性活性。

材料与方法

对商业细胞系ASC52 - telo和HDFa进行测试,将它们与化合物A和B在四种浓度下孵育:1μg/mL、2μg/mL、4μg/mL、8μg/mL,孵育48小时和72小时。进行MTT试验以评估细胞毒性并确定化合物A和B对两种受试细胞系的IC值。

结果

研究结果表明,两种受试化合物对ASC52 - telo细胞的细胞毒性活性均强于对HDFa细胞的活性。此外,与化合物B相比,化合物A对两种受试细胞系均具有更大的细胞毒性。

结论

本研究中使用的吲哚和苯并咪唑并[1,2 - c]喹唑啉可能潜在地用于基于MSCs的治疗。有必要进一步研究将MSCs用作药物载体的安全性,检查受试化合物的抗癌活性,并进行其他有价值的测定,如酶学和毒性试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6974/12168907/07ef65993723/CMAR-17-1087-g0001.jpg

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