Synthesis, In Vitro Evaluation, Molecular Docking and DFT Studies of Some Phenyl Isothiocyanates as Anticancer Agents

Author(s): Kikoleho Richa, Rituparna Karmaker, Naruti Longkumer, Vishal Das, Pulak J. Bhuyan, Mintu Pal, Upasana B. Sinha*.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 19 , Issue 18 , 2019

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Graphical Abstract:


Abstract:

Background: Isothiocyanates (ITCs) are small molecules that are important in synthetic organic chemistry, but their actual importance lies in their potential as anti-carcinogens. Through this piece of work, an effort was made to assess the anti-cancer activity of some simple ITCs which can be synthesized through easy greener pathways.

Methods: Cell proliferation assay was performed on ovarian cancer cells (PA-1) and non-tumorigenic ovarian epithelial cells (IOSE-364). Furthermore, qRT-PCR for transcript expression levels of Spindlin1 and caspases in ovarian cancer cells and cell cycle analysis was performed. In silico studies were incorporated to understand the mode of ligand-protein interaction, ADME/Toxicity and drug-likeliness parameters. Density functional theory studies have been also been employed on the ITCs to assess their efficiency in anticancer activity.

Results: An inexpensive, environmentally benign pathway has been developed for synthesizing a series of ITCs. Among the synthesized ITCs, NC6 showed better cytotoxic effects as compared to its counterparts. Novel findings revealed that NC6 had 5-folds lower transcript expression levels of Spindlin1 and induced caspases 3 and 7 expressions assessed by qRT-PCR in ovarian cancer cells. Furthermore, flow cytometry assay showed the cell cycle arrest at G1/S phase of cell cycle. The molecular docking studies revealed favorable binding affinities and the physiochemical parameters were predicted to be compatible with drug-likeliness.

Conclusion: The results demonstrated the possibility that small isothiocyanate molecules which can be synthesized by a simple green methodology, can pose as promising candidates for their application as anticancer agents.

Keywords: Synthesis, isothiocyanates, anticancer, in vitro, in silico, band gap energy.

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VOLUME: 19
ISSUE: 18
Year: 2019
Page: [2211 - 2222]
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DOI: 10.2174/1871520619666190930122137
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