Design, synthesis, and cytotoxicity of ibuprofen-appended benzoxazole analogues against human breast adenocarcinoma†

IF 3.597 Q2 Pharmacology, Toxicology and Pharmaceutics

MedChemComm Pub Date : 2024-01-02 DOI:10.1039/D3MD00479A

Vishnu Thumma, Veerabhadraiah Mallikanti, Raghavender Matta, Ravinder Dharavath and Pochampally Jalapathi

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Abstract

A library of novel ibuprofen-appended benzoxazole analogues (7a–l) was synthesized via a series of nitration, reduction, and condensation–cyclization reactions and screened for their in vitro anticancer activity against human breast cancer MCF-7 and MDA-MB-231 cell lines using doxorubicin as a standard reference. Compounds 7h and 7j displayed outstanding activity against the MCF-7 cell line with an IC₅₀ value of 8.92 ± 0.91 μM and 9.14 ± 8.22 μM, respectively, compared to the doxorubicin IC₅₀ value of 9.29 ± 1.02 μM. Compound 7h also exhibited outstanding activity against the MDA-MB-231 cell line with an IC₅₀ value of 7.54 ± 0.95 μM compared to the doxorubicin IC₅₀ value of 7.68 ± 5.36 μM. Compounds 7h, 7i, 7j, and 7g showed identical morphological changes to those showed by doxorubicin. The molecular docking study against ERα unveiled their best docking scores and binding interactions in agreement to experimental results. Pharmacokinetics prediction envisaged their drug-like properties suitable for therapeutic applications.

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布洛芬修饰的苯并恶唑类似物对人类乳腺癌的设计、合成和细胞毒性

通过一系列硝化、还原和缩合-环化反应合成了新型布洛芬修饰苯并恶唑类似物（7a-l），并以多柔比星为标准参照物筛选了它们对人类乳腺癌 MCF-7 和 MDA-MB-231 细胞系的体外抗癌活性。与多柔比星的 IC50 值 9.29 ± 1.02 μM 相比，化合物 7h 和 7j 对 MCF-7 细胞株的 IC50 值分别为 8.92 ± 0.91 μM 和 9.14 ± 8.22 μM，表现出了突出的活性。化合物 7h 对 MDA-MB-231 细胞株也表现出卓越的活性，其 IC50 值为 7.54 ± 0.95 μM，而多柔比星的 IC50 值为 7.68 ± 5.36 μM。化合物 7h、7i、7j 和 7g 显示出与多柔比星相同的形态变化。针对ERα的分子对接研究显示，这些化合物的对接得分和结合相互作用与实验结果一致。药代动力学预测认为它们具有类似药物的特性，适合用于治疗。

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来源期刊

MedChemComm BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL

CiteScore

4.70

自引率

0.00%

发文量

审稿时长

2.2 months

期刊介绍： Research and review articles in medicinal chemistry and related drug discovery science; the official journal of the European Federation for Medicinal Chemistry. In 2020, MedChemComm will change its name to RSC Medicinal Chemistry. Issue 12, 2019 will be the last issue as MedChemComm.