Investigation of triazole-linked indole and oxindole glycoconjugates as potential anticancer agents: novel Akt/PKB signaling pathway inhibitors

MedChemComm
2016.0

Abstract

In continuation of our venture towards the synthesis of novel bioactive agents, the two sets of triazole linked glycoconjugates were synthesized respectively from indole/oxindole (29 compounds) and were further characterized by IR (infrared spectroscopy), 1 H NMR (nuclear magnetic resonance), 13C NMR and mass spectral analysis. The newly synthesized target compounds were evaluated for their preliminary in vitro anticancer activity against DU145 (prostate cancer), HeLa (cervical cancer), A549 (lung cancer) and MCF-7 (breast cancer) cell lines. In the sulforhodamine B (SRB) assay, the results indicated that the compounds 5f (indole derivative) and E-9b (oxindole derivative) displayed remarkable cytotoxic activity against the DU145 cells. Moreover, the colony formation assay (soft agar assay) revealed that the compounds 5f and E-9b can inhibit the growth and proliferation of DU145 cells. The impact of the most active cytotoxic compounds 5f and E-9b on the cell cycle distribution was assessed in DU145 cells, which displayed a cell cycle arrest at the sub-G1 phase. Next, the compounds 5f and E-9b were tested for caspase activation in the DU145 cells, and the results specified that the these compounds have capability to induce apoptosis in cells through an intrinsic pathway leading to subsequent cell death. Further studies also confirmed that the compounds 5f and E-9b act against protein kinase B (Akt/PKB) pathway to inhibit proliferation of cancer cells. Thus, the compounds 5f and E-9b could be the novel potential anticancer leads as the normal cell line NIH/3T3 (fibroblast) studies showed no significant cytotoxicity.

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