Syntheses and Cytotoxicities of Quinazolinone-Based Conjugates

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL

Chemical & pharmaceutical bulletin Pub Date : 2024-01-12 DOI:10.1248/cpb.c23-00674

Hieu Trong Le, Kiep Minh Do, Quy Phu Nguyen, Chau Nguyen Minh Doan, Nhi Ai Nguyen, Tai Thi Phan, Xuyen Thi Cam Tran, Quy Thi Kim Ha, De Quang Tran, Hiroyuki Morita, Hue Thi Buu Bui

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Abstract

Two novel series of quinazolinone-based hybrids, including quinazolinone-1,3,4-oxadiazoles (10a–l) and quinazolinone-1,3,4-oxadiazole-benzimidazoles (8a–e), were designed and synthesized and their cytotoxic activities against three human cancer cell lines, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7), were evaluated. The cytotoxic assays revealed that 10i with a lipophilic 4-fluoro-phenyl moiety at the C-2 position of the quinazolinone ring displayed good cytotoxicities against the A549 and MCF-7 cell lines, while 8b–d with the thioether-linked benzimidazole moiety incorporated on the right side of the oxadiazole ring induced comparable stronger activities toward the MCF-7 cell line, relative to the simple two-heterocycle-containing hybrid 10i. These novel quinazolinone-based hybrids could be considered as lead compounds that merit further optimization and development as anti-cancer agents.

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喹唑啉酮类共轭物的合成与细胞毒性

本研究设计并合成了两个新系列的喹唑啉酮基杂交化合物，包括喹唑啉酮-1,3,4-恶二唑（10a-l）和喹唑啉酮-1,3,4-恶二唑-苯并咪唑（8a-e），并评估了它们对肺癌（A549）、宫颈癌（HeLa）和乳腺癌（MCF-7）三种人类癌细胞系的细胞毒性活性。细胞毒性试验结果表明，喹唑啉酮环 C-2 位上含有亲脂性 4-氟苯基分子的 10i 对 A549 和 MCF-7 细胞株具有良好的细胞毒性，而在草酰二唑环右侧加入硫醚连接的苯并咪唑分子的 8b-d 对 MCF-7 细胞株的活性比简单的含两个杂环的混合物 10i 更强。这些基于喹唑啉酮的新型杂交化合物可被视为先导化合物，值得进一步优化并开发为抗癌药物。

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来源期刊

Chemical & pharmaceutical bulletin 医学-化学综合

CiteScore

3.20

自引率

5.90%

发文量

132

审稿时长

1.7 months

期刊介绍： The CPB covers various chemical topics in the pharmaceutical and health sciences fields dealing with biologically active compounds, natural products, and medicines, while BPB deals with a wide range of biological topics in the pharmaceutical and health sciences fields including scientific research from basic to clinical studies. For details of their respective scopes, please refer to the submission topic categories below. Topics: Organic chemistry In silico science Inorganic chemistry Pharmacognosy Health statistics Forensic science Biochemistry Pharmacology Pharmaceutical care and science Medicinal chemistry Analytical chemistry Physical pharmacy Natural product chemistry Toxicology Environmental science Molecular and cellular biology Biopharmacy and pharmacokinetics Pharmaceutical education Chemical biology Physical chemistry Pharmaceutical engineering Epidemiology Hygiene Regulatory science Immunology and microbiology Clinical pharmacy Miscellaneous.