Synthesis, <i>In Vitro</i> 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 and Upasana B. Sinha*   Pages 2211 - 2222 ( 12 )

Abstract:

<P>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. </P><P> 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. </P><P> 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. </P><P> 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.</P>

Keywords:

Synthesis, isothiocyanates, anticancer, <i>in vitro</i>, in silico, band gap energy.

Affiliation:

Department of Chemistry, Nagaland University, Lumami-798627, Nagaland, Department of Chemistry, Nagaland University, Lumami-798627, Nagaland, Department of Chemistry, Nagaland University, Lumami-798627, Nagaland, Biological Sciences and Technology Division, Biotechnology Group, CSIR-North East Institute of Science and Technology (NEIST), Academy of Scientific and Innovative Research, Jorhat, Assam-785006, Chemical Sciences and Technology Division, CSIR- North East Institute of Science and Technology (NEIST), Jorhat, Assam-785006, Biological Sciences and Technology Division, Biotechnology Group, CSIR-North East Institute of Science and Technology (NEIST), Academy of Scientific and Innovative Research, Jorhat, Assam-785006, Department of Chemistry, Nagaland University, Lumami-798627, Nagaland

Graphical Abstract:

Read Full-Text article