Synthesis, molecular structure exploration and in vitro cytotoxicity screening of five novel N, N′- disubstituted thiocarbamide derivatives

GRAPHICAL ABSTRACT

ABSTRACT

The synthesis of five N,N″-substituted thiocarbamides, namely N-(naphthyl)-N″-(pentoxycarbonyl) thiocarbamide (H₂L1), N-(2-Chloro-4-nitrophenyl)-N″-(pentoxycarbonyl) thiocarbamide(H₂L2), N-(2-methoxy-4-nitrophenyl)-N″-(pentoxycarbonyl) thiocarbamide (H₂L3), N-(3-nitrophenyl)-N″-(pentoxycarbonyl) thiocarbamide (H₂L4) and N-(naphthyl)-N″-(2, 2, 2-trichloroethoxycarbonyl) thiocarbamide (H₂L5) was performed by the reaction of pentoxycarbonyl chloroformate with naphthyl amine, 2-chloro-4-nitroaniline, 2-methoxy-4-nitroaniline, 3-nitroaniline, respectively, for the first four and by the reaction of 2, 2, 2-trichloroethoxycarbonyl chloroformate with naphthyl amine for the last compound. These compounds were fully characterized by using various spectroscopic (FT-IR, ¹H and ¹³C NMR) and single crystal X-ray studies of H₂L1 and H₂L5. In the crystal structure of both the compounds the (C˭S) and (C˭O) groups are trans to each other across the C−N bond. The crystal packing of H₂L1 shows that the molecules form centrosymmetric dimers connected by N2−H····S hydrogen bonds. In H₂L5 an offset face-to-face π–π stacking is observed between two naphthalene rings of two molecules. In vitro cytotoxicity of synthesized compounds was evaluated using five human carcinoma cell lines 2008, C13* (cervical carcinoma), A2780, A2780/CP and IGROV-1 (ovarian carcinoma). The IC₅₀ values of compounds H₂L2 ─ H₂L4 demonstrated them to be very promising anticancer agents.

KEYWORDS:

• Thiocarbamide
• X-ray crystallography
• cytotoxicity
• spectroscopic techniques
• π─π stacking

Acknowledgements

The author, SKP is grateful to Banaras Hindu University, Varanasi, India for the financial assistance. I am thankful to Prof. G. Marverti, Department of Biomedical Sciences, Metabolic and neurosciences, University of Modena, Italy for cytotoxicity studies. I am also very thankful to Prof. R. J. Butcher, Department of Chemistry, Howard University, 525 College Street NW, Washington, DC 20059, USA for the X-ray studies.

Supplementary Information

X-ray crystallographic hydrogen bonding Table S 1 of compounds (H₂L1) and (H₂L5), Cytotoxicity Table S 2 of compounds (H₂L1−H₂L5) and Figures (S 1, S 2 and S 3) have been provided in Supporting Information.

CCDC 999080 and 999081 contain the supplementary crystallographic data for compounds (H₂L1) and (H₂L5). These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif, by e-mailing [email protected] or by contacting the Cambridge Crystallographic Data.