Inhibitory growth evaluation and apoptosis induction in MCF-7 cancer cells by new 5-aryl-2-butylthio-1,3,4-oxadiazole derivatives
Cancer has become one of the global health issues and it is the life-threatening disease characterized by unrestrained growth of cells. Despite various advances being adopted by chemotherapeutic management, the use of the current anticancer drugs such as Doxorubicin, Asparginase, Methotrexate, Vincristine remains limited due to high toxicity, side effects and developing drug resistance. Apoptosis is a crucial cellular process and improper regulation of apoptotic signaling pathways may lead to cancer formation. Subsequently, the synthesis of effective chemotherapeutic agents that can induce apoptosis in tumor cell has emerged as a significant approach in cancer drug discovery.
The goal of this work is to develop a potential antitumor agent exerting significant inhibitory effects on cancer cell and low cytotoxicity, for which we focused on the structural features of 1,3,4-oxadiazoles as it a privileged scaffold in modern medicinal chemistry and have the ability to inhibit growth factors, enzymes and kinases potentially involved in the attainment of cellular immortality and carcinogenesis.
In vitro MTT screening assay showed the compound 5-aminophenyl-2-butylthio-1,3,4-oxadiazole (5e) showing the highest inhibitory effect against MCF-7 cancer cell with IC50 value 10.05 ± 1.08 µM while it is much safer and less toxic on normal cell line (HEK-293). The dose-dependent treatment of MCF-7 cells with 5e resulted in inhibition of cell migration in the wound healing assay. The flow-cytometry analysis showed the cells arrested in G0/G1 phase of the cell cycle. Compound 5e induced apoptosis of MCF-7 cells was characterized using DAPI staining and Annexin V-PE/7-AAD dual binding assay. Reduction of NBT by compound 5e showed a reduced generation of ROS. Western blotting studies showed high activation of apoptotic protein Caspase3 and decrease in expression of anti-apoptotic protein BCL-2.
Based on the results of in vitro studies, it could be concluded that compound 5e showed a significant inhibitory growth effect on MCF-7 cells and have the potential to be developed as lead molecule and further structural modifications may result in promising new anticancer agents.
Keywords1,3,4-Oxadiazole derivatives Apoptosis Inhibition growth assay Drug-like properties
This research work had supported by UGC (F no-43-172/2014 (SR). Author Rashmin Khanam is grateful to UGC for providing NON-Net fellowship for financial support and Dr. Syed Shahabuddin for great help.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human or animal participants
This article does not contain any studies with human participants or animals performed by any of the authors.
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