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L-脯氨酸催化合成新型α-氰基双（吲哚基）查耳酮及其作为潜在抗癌剂的研究

l-Proline catalysed synthesis and studies of novel α-cyano bis(indolyl)chalcones as potential anti-cancer agents.

作者信息

Malik Monika, Roy Nandini, Sakkarai Mohamed Asha Parveen, Lotana Humphrey, Shah Kavita, Kumar Dalip

机构信息

Department of Chemistry, Birla Institute of Technology and Science Pilani 333 031 India

Department of Chemistry, Purdue University Center for Cancer Research, Purdue University West Lafayette IN 47907 USA

出版信息

RSC Adv. 2025 Feb 10;15(6):4593-4606. doi: 10.1039/d4ra06796g. eCollection 2025 Feb 6.

DOI:10.1039/d4ra06796g
PMID:39931398
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11809490/
Abstract

A diverse range of α-cyano bis(indolyl)chalcones (21a-r) were synthesized in high yields (90-95%) through the l-proline catalysed reaction of appropriate aldehydes and 3-cyanoacetylindoles. Formation of α-cyano bis(indolyl)chalcones involves readily available starting materials, catalytic l-proline, environmentally benign and metal-free conditions. The prepared eighteen α-cyano bis(indolyl)chalcones 21a-r were screened against prostate, breast, epithelial cancer cells and found to be non-cytotoxic to normal HEK293 cells. The α-cyano bis(indolyl)chalcones 21a (3.9 μM), 21c (7.5 μM), 21i (2.2 μM) and 21o (5.9 μM) displayed good cytotoxicity against C4-2 cells, whereas, derivatives 21c (1.23 μM), 21h (5.23 μM), and 21l (2.5 μM) showed selective cytotoxicity against 22Rv1 cells. With broad spectrum of activity (0.98-5.6 μM), the compound 21j was found to increase the endogenous level of ROS, upregulate the level of p-53 and c-jun besides mitochondrial dysfunction, cause apoptosis.

摘要

通过L-脯氨酸催化合适的醛与3-氰基乙酰吲哚反应，以高产率（90 - 95%）合成了多种α-氰基双（吲哚基）查耳酮（21a - r）。α-氰基双（吲哚基）查耳酮的形成涉及容易获得的起始原料、催化量的L-脯氨酸、环境友好且无金属的条件。对制备的18种α-氰基双（吲哚基）查耳酮21a - r针对前列腺癌、乳腺癌、上皮癌细胞进行筛选，发现它们对正常的HEK293细胞无细胞毒性。α-氰基双（吲哚基）查耳酮21a（3.9 μM）、21c（7.5 μM）、21i（2.2 μM）和21o（5.9 μM）对C4 - 2细胞显示出良好的细胞毒性，而衍生物21c（1.23 μM）、21h（5.23 μM）和21l（2.5 μM）对22Rv1细胞表现出选择性细胞毒性。化合物21j具有广谱活性（0.98 - 5.6 μM），被发现除了导致线粒体功能障碍外，还能增加活性氧的内源性水平、上调p - 53和c - jun的水平，从而引起细胞凋亡。

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ChemMedChem. 2024 Jan 2;19(1):e202300562. doi: 10.1002/cmdc.202300562. Epub 2023 Dec 4.
3
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