Cytotoxicity, Pro-apoptotic Activity and in silico Studies of Dithiocarbamates and their Structure Based Design and SAR Studies

(E-pub Ahead of Print)

Author(s): Syeda Shamila Hamdani , Bilal Ahmad Khan* , Shahid Hameed , Faisal Rashid , Sumera Zaib , Khalil Ahmed , Ehsan Ullah Mughal , Jamshed Iqbal* .

Journal Name: Medicinal Chemistry

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Background: Cancer is a far reaching and lethal but cureable disease. Reasearchers have investigated numerous anticancer agents with only few commercialy available effective drugs which are very costly.

Objective: Herein we report the synthesis , characterization and anti cancer assays of a series of novel dithiocarbamates derivatives.

Method: All compounds were synthesized from different secondary amines and substituted benzyl chlorides in single step. The structures of newly synthesized dithiocarbamate derivatives were confirmed by spectroscopic techniques (IR, NMR and HR-MS).

Results: The synthesized compounds showed significant anti-proliferative effect in cancer cells (HeLa) with the maximum inhibitory activity of compound SHD-2 with an IC50 = 0.31 ± 0.09 µM. However, the same compound exhibited 19.2% inhibition towards Baby Hamster Kidney fibroblasts (BHK-21), normal cell lines. Moreover, quantification of cellular DNA by flow cytometry for the evaluation of pro-apoptotic activity in HeLa cells demonstrates that arrest in cell cycle along with apoptosis advance towards drug cytotoxicity. However, molecular docking studies of the potent compound suggested that it binds to the major groove of the DNA.

Conclusion: The cytotoxic and pro-apoptotic potential of the potent inhibitor may be further investigated in the animal models to advance their anti-cancer prospective.

Keywords: dithiocarbamate, flow cytometric assay, propidium iodide staining, anti-proliferative effect

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1573406415666190211162013
Price: $95

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