Lingaraju Gejjalagere S, Balaji Kyathegowdanadoddi S, Jayarama Shankar, Anil Seegehalli M, Kiran Kuppalli R, Sadashiva Maralinganadoddi P
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India.
P.G. Department of Biotechnology, Teresian College, Mysore 570 011, India.
Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3606-3612. doi: 10.1016/j.bmcl.2018.10.046. Epub 2018 Oct 29.
A series of new coumarin tethered isoxazolines (7a-l) were synthesized and evaluated for their cytotoxic potency against human melanoma cancer cell line (UACC 903) as well as fibroblast normal cell line (FF2441). Preliminary results revealed that some of these coumarin tethered isoxazolines 7b, 7c, 7f and 7j exhibited significant antiproliferative effect against human melanoma cancer (UACC 903) with IC values of 8.8, 10.5, 9.2 and 4.5 μM respectively. However, compound 7c was non-toxic to normal human cells at the tested concentration. Further, we have chosen compound 7c to check its efficacy in Ehrlich Ascites Carcinoma animal model in-vivo for its antitumor and antiangiogenic properties. Our lead compound significantly reduced the cell viability, body weight, ascites volume and downregulated the formation of neovasculature such as regression of tumor volume. The present study indicates the scope of developing into potent anticancer drug in near future.
合成了一系列新型香豆素连接的异恶唑啉（7a - l），并评估了它们对人黑色素瘤癌细胞系（UACC 903）和成纤维细胞正常细胞系（FF2441）的细胞毒性。初步结果显示，其中一些香豆素连接的异恶唑啉7b、7c、7f和7j对人黑色素瘤癌（UACC 903）表现出显著的抗增殖作用，IC值分别为8.8、10.5、9.2和4.5 μM。然而，化合物7c在测试浓度下对正常人体细胞无毒。此外，我们选择化合物7c在艾氏腹水癌动物模型中体内检查其抗肿瘤和抗血管生成特性的功效。我们的先导化合物显著降低了细胞活力、体重、腹水体积，并下调了新血管的形成，如肿瘤体积的缩小。本研究表明在不久的将来开发成有效抗癌药物的可能性。
