Tentu Shilpa, Nandarapu Kumarswamyreddy, Muthuraj Prakash, Venkitasamy Kesavan, Venkatraman Ganesh, Rayala Suresh K
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras (IITM), Chennai, India.
Department of Human Genetics, College of Biomedical Sciences, Technology and Research, Sri Ramachandra University, Porur, Chennai, India.
J Cell Physiol. 2018 Mar;233(3):2613-2628. doi: 10.1002/jcp.26139. Epub 2017 Sep 7.
A series of 2, 3-dihydroquinazolinone derivatives were synthesized, characterized and their anticancer activity was determined. Among the compounds synthesized and screened, one compound (17) showed potent anticancer activity against human head and neck squamous cell carcinoma cell line, SCC131 and was non-toxic to normal cells. The compound inhibited the growth of SCC131 cells, with an IC of 1.75 μM, triggered apoptotic mode of cell death and caused tumor regression of SCC131 tumor xenografts in athymic mice. To decipher the target for the lead compound, a high throughput qPCR array was performed. Results showed that the compound 17, inhibited the expression of a vital transcription factor HNF4A, involved in regulation of metabolic pathways. Thus, the present work has identified a lead compound 17, with potent anticancer activity, minimal normal cell toxicity and a plausible target and hence definitely holds future prospects as an anticancer agent.
合成了一系列2,3-二氢喹唑啉酮衍生物，对其进行了表征并测定了它们的抗癌活性。在合成和筛选的化合物中，一种化合物（17）对人头颈鳞状细胞癌细胞系SCC131显示出强效抗癌活性，且对正常细胞无毒。该化合物抑制SCC131细胞的生长，IC50为1.75 μM，引发细胞凋亡的死亡模式，并导致无胸腺小鼠体内SCC131肿瘤异种移植瘤消退。为了解析先导化合物的靶点，进行了高通量qPCR阵列分析。结果表明，化合物17抑制了一种参与代谢途径调节的重要转录因子HNF4A的表达。因此，本研究确定了一种先导化合物17，它具有强效抗癌活性、对正常细胞毒性极小且有一个合理的靶点，因此作为一种抗癌剂肯定具有未来前景。
