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含苯磺酰胺咪唑衍生物在三阴性乳腺癌和黑色素瘤二维及三维细胞培养中的活性探究

Exploration of Benzenesulfonamide-Bearing Imidazole Derivatives Activity in Triple-Negative Breast Cancer and Melanoma 2D and 3D Cell Cultures.

作者信息

Balandis Benas, Mickevičius Vytautas, Petrikaitė Vilma

机构信息

Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, LT-50254 Kaunas, Lithuania.

Laboratory of Drug Targets Histopathology, Institute of Cardiology, Lithuanian University of Health Sciences, Sukilėlių pr. 13, LT-50162 Kaunas, Lithuania.

出版信息

Pharmaceuticals (Basel). 2021 Nov 13;14(11):1158. doi: 10.3390/ph14111158.

Abstract

Heterocyclic compounds are one of the main groups of organic compounds possessing wide range of applications in various areas of science and their derivatives are present in many bioactive structures. They display a wide variety of biological activities. Recently, more and more attention has been focused to such heterocyclic compounds as azoles. In this work, we have synthesized a series of new imidazole derivatives incorporating a benzenesulfonamide moiety in their structure, which then were evaluated for their cytotoxicity against human triple-negative breast cancer MDA-MB-231 and human malignant melanoma IGR39 cell lines by MTT assay. Benzenesulfonamide-bearing imidazole derivatives containing 4-chloro and 3,4-dichlorosubstituents in benzene ring, and 2-ethylthio and 3-ethyl groups in imidazole ring have been determined as the most active compounds. Half-maximal effective concentration (EC) of the most cytotoxic compound was 27.8 ± 2.8 µM against IGR39 cell line and 20.5 ± 3.6 µM against MDA-MB-231 cell line. Compounds reduced cell colony formation of both cell lines and inhibited the growth and viability of IGR39 cell spheroids more efficiently compared to triple-negative breast cancer spheroids.

摘要

杂环化合物是有机化合物的主要类别之一,在各个科学领域都有广泛应用,其衍生物存在于许多生物活性结构中。它们具有多种多样的生物活性。最近,越来越多的注意力集中在诸如唑类的杂环化合物上。在这项工作中,我们合成了一系列结构中含有苯磺酰胺部分的新型咪唑衍生物,然后通过MTT法评估了它们对人三阴性乳腺癌MDA-MB-231和人恶性黑色素瘤IGR39细胞系的细胞毒性。已确定在苯环中含有4-氯和3,4-二氯取代基以及在咪唑环中含有2-乙硫基和3-乙基的含苯磺酰胺咪唑衍生物为活性最强的化合物。最具细胞毒性的化合物对IGR39细胞系的半数最大有效浓度(EC)为27.8±2.8μM,对MDA-MB-231细胞系为20.5±3.6μM。这些化合物减少了两种细胞系的细胞集落形成,并且与三阴性乳腺癌球体相比,更有效地抑制了IGR39细胞球体的生长和活力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8892/8625351/4a31ac589440/pharmaceuticals-14-01158-g001.jpg

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