Chitosan functionalized thiophene-2-thiosemicarbazones, and their copper(II) complexes: synthesis, characterization, and anticancer activity

Abstract

Chitosan is a polyfunctional biomaterial that is subjected to chemical modification through functionalization to give the derivatives of remarkable anticancer activity. In this study, functionalization of low molecular weight commercial chitosan (CS) (Mw < 3000 Da, 87% DDA) and high molecular weight crab shell chitosan (CCS) (viscosity average Mw 350 kDa, 67% DDA) as chitosan thiophene-2-thiosemicarbazones (DS 63.48–64.14%) and the formation of their copper(II) complexes were established by FT-IR, ¹³C NMR, EPR spectroscopy, powder X ray diffraction, elemental microanalysis and magnetic susceptibility measurements. The thermal study of the compounds showed a substantial stability up to 200°C until the commencement of chitosan chain degradation. The MTT assay revealed higher activity of CS (IC₅₀ 370 μgmL⁻¹ in MCF-7 and >400 μgmL⁻¹ in MDCK cell line) than CCS (IC₅₀ > 400 μgmL⁻¹ in both cell lines), higher activity of CSTHPTSC (IC₅₀ 364 μgmL⁻¹ in MDCK and 369 μgmL⁻¹ in MCF-7 cell line) than CCSTHPTSC (IC₅₀ > 400 μgmL⁻¹ in both cell lines), higher activity of the complexes Cu-CSTHPTSC (IC₅₀ 338 μgmL⁻¹ in MDCK and 318 μgmL⁻¹ in MCF-7 cell line) and Cu-CCSTHPTSC (IC₅₀ 293 μgmL⁻¹ in MDCK and >400 μgmL⁻¹ in MCF-7 cell line) than their corresponding ligands.

Graphical Abstract

Keywords:

• Anticancer activity
• characterization
• chitosan
• chitosan thiophene-2-thiosemicarbazones
• copper(II) chitosan thiophene-2-thiosemicarbazones
• thiophene-2-carboxaldehyde

Acknowledgments

We acknowledge Nepal Academy of Science and Technology (NAST) for Ph. D. fellowship-2017 to the first author (HSA). Our acknowledgements are further extended to NAST, Indian National Science Academy (INSA) and Professor A. R. Chakravarty, Department of Inorganic and Physical Chemistry, IISc, Bangalore, India for research exchange fellowship to the first author. We are thankful to Dr Agni Koirala, Sogang University, Department of Chemistry, Korea Center for Artificial Photosynthesis (KCAP), Centre for Nanomaterial, Shinsu-dong, Mapogo, South Korea for providing with EPR spectroscopic and thermal data. We acknowledge Central Department of Biotechnology, Tribhuvan University, Kathmandu, Nepal and Head of the Department, Professor Dr Krishna Das Manandhar for the arrangement of anticancer screening.

Disclosure statement

The authors declare that there is no conflict of interest regarding the publication of this article.

Additional information

Funding

We acknowledge Nepal Academy of Science and Technology (NAST) for Ph. D. fellowship-2017 to the first author (HSA). Our acknowledgements are further extended to NAST, Indian National Science Academy (INSA) and Professor A. R. Chakravarty, Department of Inorganic and Physical Chemistry, IISc, Bangalore, India for research exchange fellowship to the first author. We are thankful to Dr Agni Koirala, Sogang University, Department of Chemistry, Korea Center for Artificial Photosynthesis (KCAP), Centre for Nanomaterial, Shinsu-dong, Mapogo, South Korea for providing with EPR spectroscopic and thermal data. We acknowledge Central Department of Biotechnology, Tribhuvan University, Kathmandu, Nepal and Head of the Department, Professor Dr Krishna Das Manandhar for the arrangement of anticancer screening.