Anticancer properties, apoptosis and catecholase mimic activities of dinuclear cobalt(II) and copper(II) Schiff base complexes

M Naqi Ahamad; Khushboo Iman; Md Kausar Raza; Manjeet Kumar; Azaj Ansari; Musheer Ahmad; M Shahid

doi:10.1016/j.bioorg.2019.103561

Anticancer properties, apoptosis and catecholase mimic activities of dinuclear cobalt(II) and copper(II) Schiff base complexes

Bioorg Chem. 2020 Jan:95:103561. doi: 10.1016/j.bioorg.2019.103561. Epub 2019 Dec 29.

Authors

M Naqi Ahamad¹, Khushboo Iman¹, Md Kausar Raza², Manjeet Kumar³, Azaj Ansari³, Musheer Ahmad⁴, M Shahid⁵

Affiliations

¹ Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
² Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangaluru, India.
³ Department of Chemistry, Central University of Haryana, Mahendergarh 123031, Haryana, India.
⁴ Department of Applied Chemistry (ZHCET), Aligarh Muslim University, Aligarh 202002, India.
⁵ Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India. Electronic address: shahid81chem@gmail.com.

PMID: 31935603
DOI: 10.1016/j.bioorg.2019.103561

Abstract

The present work describes coordination chemistry and biological evaluation of two novel dinuclear complexes [Co₂(HL¹)₂(H₂O)₂]·8H₂O (1) and [Cu₂(L²)₂] (2) obtained from the Schiff base ligands, H₃L¹ and H₂L² (formed in situ). The two complexes are characterized by single crystal X-ray, spectral and variable temperature magnetic and theoretical (DFT/TDDFT) analysis. X-ray analysis confirms both the complexes to be dinuclear with distorted octahedral and square pyramidal geometry around Co(II) and Cu(II) ions, respectively. Magnetic studies reveal presence of moderate ferromagnetic interactions in both the complexes with J = 98 (1) and 32 (2) cm^-1. The magnetic interactions are further corroborated by DFT studies. Co(II) complex (1) exhibited enhanced catecholase activity with K_cat = 213.48 h^-1, which is attributed to the greater extent of charge contribution on Co²⁺ as compared to Cu²⁺ as determined by DFT calculations. Furthermore, both the complexes show potent anticancer activity toward HeLa (cervical) and A549 (lung) cancer cell lines with IC₅₀ = 6-7 µM at 48 h, which ascertains both the complexes as better anticancer drugs than cisplatin. Furthermore, 1 and 2 exhibit apoptosis of HeLa cells by demonstrating nuclear blebbings with shrinking morphology. Hence, the present complexes could be employed as a model for metalloenzymes as well as potential anticancer substituents of cisplatin in future course.

Keywords: Anticancer activity; Apoptosis; Catecholase activity; DFT; Schiff base complexes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Catechol Oxidase / metabolism*
Cell Line, Tumor
Cobalt / chemistry*
Coordination Complexes / chemistry
Coordination Complexes / pharmacology*
Copper / chemistry*
Crystallography, X-Ray
Density Functional Theory
Humans
Molecular Mimicry*
Molecular Structure
Schiff Bases / chemistry*
Spectrum Analysis / methods

Substances

Antineoplastic Agents
Coordination Complexes
Schiff Bases
Cobalt
Copper
Catechol Oxidase