Aksenov Alexander V, Smirnov Alexander N, Magedov Igor V, Reisenauer Mary R, Aksenov Nicolai A, Aksenova Inna V, Pendleton Alexander L, Nguyen Gina, Johnston Robert K, Rubin Michael, De Carvalho Annelise, Kiss Robert, Mathieu Véronique, Lefranc Florence, Correa Jaime, Cavazos David A, Brenner Andrew J, Bryan Brad A, Rogelj Snezna, Kornienko Alexander, Frolova Liliya V
Department of Chemistry, North Caucasus Federal University , 1a Pushkin St., Stavropol 355009, Russian Federation.
J Med Chem. 2015 Mar 12;58(5):2206-20. doi: 10.1021/jm501518y. Epub 2015 Feb 20.
Many types of tumor, including glioma, melanoma, non-small cell lung, esophageal, and head and neck cancer, among others, are intrinsically resistant to apoptosis induction and poorly responsive to current therapies with proapoptotic agents. In addition, tumors often develop multidrug resistance based on the cellular efflux of chemotherapeutic agents. Thus, novel anticancer agents capable of overcoming these intrinsic or developed tumor resistance mechanisms are urgently needed. We describe a series of 2-aryl-2-(3-indolyl)acetohydroxamic acids that are active against apoptosis- and multidrug-resistant cancer cells as well as glioblastoma neurosphere stemlike cell cultures derived from patients. Thus, the described compounds serve as a novel chemical scaffold for the development of potentially highly effective clinical cancer drugs.
许多类型的肿瘤，包括神经胶质瘤、黑色素瘤、非小细胞肺癌、食管癌和头颈癌等，本质上对凋亡诱导具有抗性，并且对目前使用促凋亡药物的治疗反应不佳。此外，肿瘤常常基于化疗药物的细胞外排而产生多药耐药性。因此，迫切需要能够克服这些内在或产生的肿瘤耐药机制的新型抗癌药物。我们描述了一系列2-芳基-2-(3-吲哚基)乙酰氧肟酸，它们对凋亡和多药耐药癌细胞以及源自患者的胶质母细胞瘤神经球样干细胞培养物具有活性。因此，所描述的化合物作为一种新型化学支架，用于开发潜在高效的临床癌症药物。
