Activity of 2-aryl-2-(3-indolyl)acetohydroxamates against drug-resistant cancer cells.
Aksenov AV, Smirnov AN, Magedov IV, Reisenauer MR, Aksenov NA, Aksenova IV, Pendleton AL, Nguyen G, Johnston RK, Rubin M, De Carvalho A, Kiss R, Mathieu V, Lefranc F, Correa J, Cavazos DA, Brenner AJ, Bryan BA, Rogelj S, Kornienko A, Frolova LV.
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.