Abstract
Background: Cancer is a far-reaching and lethal but curable disease. Researchers have
investigated numerous anticancer agents with only a few commercially 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.
Methods: All compounds were synthesized from different secondary amines and substituted benzyl
chlorides in a single step. The structures of newly synthesized dithiocarbamate derivatives
were confirmed by spectroscopic techniques (IR, NMR and HR-MS).
Results: The synthesized compounds showed a 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, cancer, flow cytometric assay, propidium iodide staining, anti-proliferative effect, cancer.
Graphical Abstract
[18]
Tripathi, R.P. Khan, A. R.; Srinivasan Setty, B.; Bhaduri, A. P., Syntheses and spermicidal activities of dithiocarbamates. Acta Pharm., 1996, 46(3), 169-176.
[25]
(a)Zahran, M.A-H.; Salem, T.A-R.; Samaka, R.M.; Agwa, H.S.; Awad, A.R. Design, synthesis and antitumor evaluation of novel thalidomide dithiocarbamate and dithioate analogs against Ehrlich ascites carcinoma-induced solid tumor in Swiss albino mice.
Bioorg. Med. Chem., 2008,
16(22), 9708-9718.
[
http://dx.doi.org/10.1016/j.bmc.2008.09.071] [PMID:
18951804]
(b)Huang, W.; Ding, Y.; Miao, Y.; Liu, M-Z.; Li, Y.; Yang, G-F. Synthesis and antitumor activity of novel dithiocarbamate substituted chromones.
Eur. J. Med. Chem., 2009,
44(9), 3687-3696.
[
http://dx.doi.org/10.1016/j.ejmech.2009.04.004] [PMID:
19410339]
(c)Cao, S-L.; Feng, Y-P.; Jiang, Y-Y.; Liu, S-Y.; Ding, G-Y.; Li, R-T. Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives with dithiocarbamate side chains.
Bioorg. Med. Chem. Lett., 2005,
15(7), 1915-1917.
[
http://dx.doi.org/10.1016/j.bmcl.2005.01.083] [PMID:
15780632]
(d)Cao, S.L.; Feng, Y.P.; Zheng, X.L.; Jiang, Y.Y.; Zhang, M.; Wang, Y.; Xu, M. Synthesis of substituted benzylamino- and heterocyclylmethylamino carbodithioate derivatives of 4-(3H)-quinazolinone and their cytotoxic activity.
Arch. Pharm. (Weinheim), 2006,
339(5), 250-254. PMID: 15780632
[
http://dx.doi.org/10.1002/ardp.200500264] [PMID:
16619282]
(e)Wang, X-J.; Xu, H-W.; Guo, L-L.; Zheng, J-X.; Xu, B.; Guo, X.; Zheng, C-X.; Liu, H-M. Synthesis and in vitro antitumor activity of new butenolide-containing dithiocarbamates.
Bioorg. Med. Chem. Lett., 2011,
21(10), 3074-3077.
[
http://dx.doi.org/10.1016/j.bmcl.2011.03.029] [PMID:
21486694]
(f)Duan, Y-C.; Zheng, Y-C.; Li, X-C.; Wang, M-M.; Ye, X-W.; Guan, Y-Y.; Liu, G-Z.; Zheng, J-X.; Liu, H-M. Design, synthesis and antiproliferative activity studies of novel 1,2,3-triazole-dithiocarbamate-urea hybrids.
Eur. J. Med. Chem., 2013,
64, 99-110.
[
http://dx.doi.org/10.1016/j.ejmech.2013.03.058] [PMID:
23644193]
(g)Aly, A.A.; Brown, A.B.; Bedair, T.M.; Ishak, E.A. Dithiocarbamate salts: biological activity, preparation, and utility in organic synthesis.
J. Sulfur Chem., 2012,
33(5), 605-617.
[
http://dx.doi.org/10.1080/17415993.2012.718349]
Download PDF Flyer