Synthesis and biological evaluation of certain hydrazonoindolin-2-one derivatives as new potent anti-proliferative agents. (1st January 2018)

• Record Type: Journal Article
• Authors: Eldehna, Wagdy M.; Al-Wabli, Reem I.; Almutairi, Maha S.; Keeton, Adam B.; Piazza, Gary A.; Abdel-Aziz, Hatem A.; Attia, Mohamed I.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 33:Number 1(2018)
• Page Start: 867
• Page End: 878
• Publication Date: 2018-01-01
• Subjects: Synthesis -- indolin-2-one -- retinoblastoma (Rb) protein -- multidrug resistant cancer cell lines -- cell cycle progression; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2018.1462802
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: In connection with our research program on the development of novel indolin-2-one-based anticancer candidates, herein we report the design and synthesis of different series of hydrazonoindolin-2-ones3a-e, 5a-e, 7a-c, and10a-l . The synthesised derivatives were in vitro evaluated for their anti-proliferative activity towards lung A-549, colon HT-29, and breast ZR-75 human cancer cell lines. Compounds5b, 5c, 7b, and10e emerged as the most potent derivatives with average IC50 values of 4.37, 2.53, 2.14, and 4.66 µM, respectively, which are superior to Sunitinib (average IC50 = 8.11 µM). Furthermore, compounds7b and10e were evaluated for their effects on cell cycle progression and levels of phosphorylated retinoblastoma (Rb) protein in the A-549 cancer cell line. Moreover, 7b and10e inhibited the cell growth of the multidrug-resistant lung cancer NCI-H69AR cell line with IC50 = 16 µM. In addition, the cytotoxic activities of7b and10e were assessed towards three non-tumorigenic cell lines (Intestine IEC-6, Breast MCF-10A, and Fibroblast Swiss-3t3) where both compounds displayed mean tumor selectivity index (1.6 and 1.8) higher than that of Sunitinib (1.4). Graphical Abstract: