Search

A series of C 5 -tethered Indolyl-3-glyoxylamide derivatives were synthesized and evaluated for their in vitro cytotoxic activity against DU145 (prostate), PC-3 (prostate), A549 (lung) and HCT-15 (colon) cancer cell lines by employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized compounds, compound 7f displayed cytotoxicity of IC 50  = 140 nM towards DU145 cancer cell line. The treatment of DU145 cells with 7f led to inhibition of cell migration ability. Futher, the detailed studies such as acridine orange/ethidium Bromide (AO/EB), DAPI, annexin V-FITC/propidium iodide staining assay suggested that the compound 7f induced apoptosis in DU145 cells. The influence of the cytotoxic compound 7f on the cell cycle distribution was assessed on the DU145 cell line, exhibiting a cell cycle arrest at the G2/M phase (hallmark of tubulin polymerization) and next inhibited tubulin polymerization with IC 50 0.40 μM. Furthermore, the treatment with compound 7f caused collapse of mitochondrial membrane potential and elevated intracellular superoxide ROS levels in DU145 cells. Western blotting was performed to examine the levels of apoptotic proteins (Bcl-2 and Bax); the study confirmed that compound 7f induced apoptosis through apoptosis-related protein expression. Thus, these studies provided a new molecular scaffold for the further development of anticancer agents that target tubulin., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

In furtherance of our endeavour towards the synthesis of novel bioactive agents, a panel of (E)-3-((7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)methylene)indolin-2-one derivatives were synthesized using diverse 5-substituted oxindoles and 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde (3a). These synthesized analogues were further evaluated for their in vitro cytotoxic activity against MDA-MB-231 (breast), MCF-7 (breast), DU145 (prostate), PC-3 (prostate) and A549 (lung) cancer cell lines by employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized compounds, compounds 7q (IC50 = 9.52 and 9.9 μM) and 7r (IC50 = 15.3 and 11.7 μM) showed the most significant cytotoxicity towards DU145 and PC-3 cancer cell lines respectively. Compounds 7q and 7r were found to be comparatively safe towards normal human prostate epithelial (RWPE-1) cells. The apoptosis inducing effect of compounds 7q and 7r on PC-3 and DU145 cancer cells was further investigated using the annexin V-FITC/propidium iodide staining assay, which confirmed the increase in the percentage of early apoptotic cells. Moreover, the cell cycle analysis revealed cell cycle arrest particularly at the G0/G1 phase in the PC-3 and DU145 cells. In addition, the treatment with compounds 7q and 7r led to collapse of the mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) in the PC-3 and DU145 cells. Western blotting was performed to examine the appearance of active forms of cytochrome c and cleaved PARP (Poly ADP ribose polymerase), indicator proteins of apoptosis in PC-3 cells; the study confirmed the triggering of the mitochondrial mediated apoptotic pathway upon exposure to compounds 7q and 7r. [ABSTRACT FROM AUTHOR]

In our endeavor towards the development of effective cytotoxic agents, a series of oxindole linked indolyl-pyrimidine derivatives were synthesized and characterized by IR, 1 H NMR, 13 C NMR and Mass spectral analysis. All the newly synthesized target compounds were assessed against PA-1 (ovarian), U-87MG (glioblastoma), LnCaP (prostate), and MCF-7 (Breast) cancer cell lines for their cytotoxic potential, with majority of them showing inhibitory activity at low micro-molar concentrations. Significantly, compound 8e was found to be most potent amongst all the tested compounds with an IC 50 value of (2.43 ± 0.29 μM) on PA-1 cells. The influence of the most active cytotoxic compound 8e on the cell cycle distribution was assessed on the PA-1 cell line, exhibiting a cell cycle arrest at the G2/M phase. Moreover, acridine orange/ethidium bromide staining and annexin V binding assay confirmed that compound 8e can induce cell apoptosis in PA-1 cells. These preliminary results persuade further investigation on the synthesized compounds aiming to the development of potential cytotoxic agents. [ABSTRACT FROM AUTHOR]