Department of Chemistry, School of Science, GITAM (Deemed to be University), Hyderabad, Telangana, 502 329, India.
School of Chemistry & Physics, College of Agriculture, Engineering & Science, Westville Campus, University of KwaZulu-Natal, P Bag X 54001, Durban 4000, South Africa.
Anticancer Agents Med Chem. 2019;19(16):2001-2009. doi: 10.2174/1871520619666190723151909.
Compounds containing the quinazoline-4(3H)-one framework constitute an important class of fused N-heterocycles that are found in more than 200 naturally occurring alkaloids. These compounds also show a diverse range of pharmacological activities including antitumor properties. This prompted us to explore a series of quinazolin-4-(3H)-one derivatives having no substituent at C-2 as potential cytotoxic agents.
The objective of this study was to synthesize and evaluate 3-substituted quinazolin-4(3H)-one derivatives for their potential cytotoxic properties.
A convenient method has been developed for the rapid synthesis of this class of compounds under a mild and non-hazardous reaction condition in good yields. The methodology involved a three-component reaction employing isatoic anhydride, amines and glyoxylic acid as reactants in the presence of lemon juice in PEG- 400 at room temperature (25-30ºC) under ultrasound irradiation. All the synthesized compounds were screened via an MTT assay for their potential cytotoxic properties in vitro using the cancerous cell lines e.g. A549, A2780, HepG2, K562, MCF-7 and HCT-116 and a non-cancerous HEK293 cell line.
Several compounds such as 3a, 3b, 3d, 3e and 3f showed promising growth inhibition against these cancer cell lines but no significant effects on HEK293 cell line. The IC50 values of these compounds were comparable to doxorubicin whereas 3f significantly induced apoptosis in MCF-7 cells that also was comparable to doxorubicin.
An ultrasound-assisted MCR facilitated by lemon juice has been developed to synthesize 3- substituted quinazolin-4(3H)-one derivatives that could act as potential anticancer agents.
含有喹唑啉-4(3H)-酮骨架的化合物构成了一类重要的稠合 N-杂环，存在于 200 多种天然存在的生物碱中。这些化合物还表现出多种药理活性，包括抗肿瘤特性。这促使我们探索一系列无 C-2 取代基的喹唑啉-4-(3H)-酮衍生物作为潜在的细胞毒性剂。
本研究的目的是合成和评估 3-取代的喹唑啉-4(3H)-酮衍生物的潜在细胞毒性。
开发了一种简便的方法，在温和且无危险的反应条件下，在柠檬酸钠存在下，PEG-400 中以良好的产率快速合成这类化合物。该方法涉及使用异吲哚-1,3-二酮、胺和乙醛酸作为反应物，在室温（25-30°C）下在超声辐射下进行三组分反应。所有合成的化合物均通过 MTT 测定法在体外进行筛选，以评估其在癌细胞系（如 A549、A2780、HepG2、K562、MCF-7 和 HCT-116）和非癌细胞系 HEK293 中的潜在细胞毒性。
几种化合物，如 3a、3b、3d、3e 和 3f，对这些癌细胞系表现出有希望的生长抑制作用，但对 HEK293 细胞系没有显著影响。这些化合物的 IC50 值与多柔比星相当，而 3f 显著诱导 MCF-7 细胞凋亡，与多柔比星相当。
开发了一种由柠檬汁辅助的超声辅助 MCR，用于合成可能作为潜在抗癌剂的 3-取代喹唑啉-4(3H)-酮衍生物。
