ABSTRACT
On account of their significance as apoptosis inducing agents, merging indole and 3-hydrazinoindolin-2-one scaffolds is a logic tactic for designing pro-apoptotic agents. Consequently, 27 hybrids (6a-r, 9a-f and 11a-c) were synthesised and evaluated for their cytotoxicity against MCF-7, HepG-2 and HCT-116 cancer cell lines. SAR studies unravelled that N-propylindole derivatives were the most active compounds such as 6n (MCF-7; IC50=1.04 µM), which displayed a significant decrease of cell population in the G2/M phase and significant increase in the early and late apoptosis by 19-folds in Annexin-V-FTIC assay. Also, 6n increased the expression of caspase-3, caspase-9, cytochrome C and Bax and decreased the expression of Bcl-2. Moreover, compounds 6i, 6j, 6n and 6q generated ROS by significant increase in the level of SOD and depletion of the levels of CAT and GSH-Px in MCF-7.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Drug Design , Hydrazones/pharmacology , Indoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HCT116 Cells , Hep G2 Cells , Humans , Hydrazones/chemical synthesis , Hydrazones/chemistry , Indoles/chemical synthesis , Indoles/chemistry , MCF-7 Cells , Molecular Structure , Oxidative Stress/drug effects , Structure-Activity RelationshipABSTRACT
In this work, we studied simultaneous effect of gamma irradiation and SrO substitution for Na2 O on bioactivity, cytotoxicity and antimicrobial properties of 45S5 glass. Gamma irradiation was mainly introduced in this work as an effective sterilizing technique, improvement of bulk properties and surface modification of glass. Where, gamma irradiation is considered a modifier for glass network due to generation of defects resulted from this irradiation. Furthermore, SrO was introduced into the glass structure in place of Na2 O in order to reduce a probable toxic effect of Na2 O for surrounding tissue by decreasing its percentage. Where, Sr2+ is characterized by its antibacterial properties, as well as, it induces formation of bone tissue and inhibits its resorption. The cell viability was studied for selected samples using Vero cells. As well as, antimicrobial activity was evaluated against Bacillus subtilis, Staphylococcus pneumonia, and Escherichia coli and Pseudomonas aeruginosa bacteria. The results showed that substitution of Na2 O by SrO in glass composition decreased the glass dissolution in SBF. However, the glass dissolution increased after irradiation of such glass due to generation of nonbridgingoxygens (NBOs) throughout glass network by gamma irradiation, and this effect was more obvious for Sr-contained glass. On the other hand, two selected Sr-containing glasses (gamma irradiated at 0 and 25 kGy) showed a good ability to stimulate cell proliferation of normal fibroblast cells, as well as, they represented a potential ability to inhibit the growth of or kill bacteria, which is considered an important issue commonly found in a clinical situation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1646-1655, 2017.
