N-substitution in isatin thiosemicarbazones decides nuclearity of Cu(II) complexes - Spectroscopic, molecular docking and cytotoxic studies

Jebiti Haribabu; Othman I Alajrawy; Kumaramangalam Jeyalakshmi; Chandrasekar Balachandran; Dhanabalan Anantha Krishnan; Nattamai Bhuvanesh; Shin Aoki; Karuppannan Natarajan; Ramasamy Karvembu

doi:10.1016/j.saa.2020.118963

N-substitution in isatin thiosemicarbazones decides nuclearity of Cu(II) complexes - Spectroscopic, molecular docking and cytotoxic studies

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Feb 5:246:118963. doi: 10.1016/j.saa.2020.118963. Epub 2020 Sep 18.

Authors

Jebiti Haribabu¹, Othman I Alajrawy², Kumaramangalam Jeyalakshmi³, Chandrasekar Balachandran⁴, Dhanabalan Anantha Krishnan⁵, Nattamai Bhuvanesh⁶, Shin Aoki⁷, Karuppannan Natarajan⁸, Ramasamy Karvembu⁹

Affiliations

¹ Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India; Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan.
² College of Applied Science, Department of Applied Chemistry, University of Fallujah, Fallujah 00964, Iraq.
³ Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India; Department of Chemistry, M. Kumarasamy College of Engineering, Karur 639113, India.
⁴ Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan.
⁵ Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, India.
⁶ Department of Chemistry, Texas A & M University, College Station, TX 77842, USA.
⁷ Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan; Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan.
⁸ Department of Chemistry, Sri Ramakrishna Mission Vidyalaya College of Arts and Science, Coimbatore 641 020, India.
⁹ Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India. Electronic address: kar@nitt.edu.

PMID: 33017789
DOI: 10.1016/j.saa.2020.118963

Abstract

The mono- (1) and bi-nuclear (2) copper(II) complexes containing N-substituted isatin thiosemicarbazone(s) were synthesized, and characterized by analytical and spectroscopic (UV-Visible, FT-IR and EPR) techniques. Bimetallic nature of complex 2 was confirmed by single crystal X-ray crystallography. The structures predicted by spectroscopic and crystallographic methods were validated by computational studies. From the spectroscopic, crystallographic and computational data, the structures were found to be distorted square planar for 1 and distorted square pyramidal for 2. Molecular docking studies showed hydrogen bonding and hydrophobic interactions of the complexes with tyrosinase kinase receptors. Complex 1 exhibited promising cytotoxic activity against Jurkat (leukemia) cell line, and complex 2 displayed more activity against HeLa S3 (cervical) and Jurkat cell lines with the IC₅₀ values of 3.53 and 3.70 μM, respectively. Cytotoxicity of 1 (Jurkat) and 2 (Jurkat and HeLa S3) was better than that of cisplatin. Morphological changes in A549 (lung), HeLa S3 and Jurkat cell lines were examined in presence of the active complexes with the co-staining of Hoechst, AO (acridine orange) and EB (ethidium bromide) by fluorescence microscope.

Keywords: Cu(II) complexes; Cytotoxicity; Molecular docking; Spectroscopy; Theoretical calculations; Thiosemicarbazones.

MeSH terms

Antineoplastic Agents* / pharmacology
Coordination Complexes* / pharmacology
Copper
Crystallography, X-Ray
Isatin* / pharmacology
Molecular Docking Simulation
Spectroscopy, Fourier Transform Infrared
Thiosemicarbazones* / pharmacology

Substances

Antineoplastic Agents
Coordination Complexes
Thiosemicarbazones
Copper
Isatin