DNA binding and in vitro anticancer activity of 2‐((1H‐benzimidazol‐2‐yl)methylamino)acetic acid and its copper(II) mixed‐polypyridyl complexes: Synthesis and crystal structure

Abstract

New copper(II) ternary complexes formulated as [Cu(N‐N)BIG]ClO4, where BIG is deprotonated 2‐((1H‐benzimidazol‐2‐yl)methylamino)acetic acid and N‐N represents 2,2′‐bipyridine (1) or 4,4′‐dimethyl‐2,2′‐bipyridine (2) or 5,5′‐dimethyl‐2,2′‐bipyridine (3) or 1,10‐phenanthroline (4) or 4,5‐diazafluoren‐9‐one (5) or dipyridylamine (6), were synthesized and characterized using analytical and spectral methods. Complex 1 was characterized using single‐crystal X‐ray diffraction analysis and found to be monomeric in nature with distorted square pyramidal geometry. The binding interactions of 1–6 with calf thymus DNA were studied using UV–visible absorption and emission spectroscopy and viscosity measurements. The DNA cleavage ability of 1–6 with pUC19 DNA shows that the complexes can cleave DNA without any external agents. The ligand and complexes were investigated for their in vitro antibacterial activity against Bacillus subtilis and Staphylococcus aureus. The complexes showed enhanced antibacterial activities compared to the free ligand. Molecular docking studies of complexes 1–6 were made using Genetic Optimization of Ligand Docking (GOLD) software. The study indicated that LEU23, ASP25, ILE84, ASN144 and ARG87 of COX‐2 were important for strong hydrogen bonding interaction with the complexes. Among the complexes, 2 showed the best docking result with COX‐2. Cytotoxicity assay was performed using MTT reagent against human cervical cancer cells, human breast cancer cells and human lung cancer cells. The complexes were found to show moderate anticancer activity.

Synthesis, Characterization, and Antiproliferative Activity Studies of Novel Benzimidazole‐Imidazopyridine Hybrids as DNA Groove Binders

“…The value of the intrinsic binding constant K b for compounds 1 and 2 were derived to be 0.4 (± 0.06) × 10 5 M −1 and 1.5 (± 0.3) × 10 5 M −1 , respectively. These values are weaker or comparable to those of the other benzimidazole compounds …”

“…have created indispensable examples for development of new therapeutic agents . A great number of 2‐substituted benzimidazoles have been synthesized and their biological activities reported (Figure ) . A number of these studies has also focused on symmetrical and unsymmetrically substituted bis‐benzimidazoles .…”

Benzimidazole based derivatives as anticancer agents: Structure activity relationship analysis for various targets

“…Sabithakala et al [90] synthesized copper (II) complexes with general representation [Cu(N‐N)BIG]ClO 4 where BIG represents deprotonated 2‐((1 H ‐benzimidazol‐2‐yl)methyl amino)acetic acid and N ‐ N represents different substituent groups. The synthesized complexes were screened for their anticancer properties and pro‐apoptotic potential against HeLa (cervical), MCF‐7 (breast), A549 (lung) human cancer cell lines, and normal HEK 293 (embryonic kidney) cell line by performing MTT assay with doxorubicin as the reference drug.…”

Copper Coordination Compounds as Biologically Active Agents

“…Development of novel copper coordination compounds with antitumor activity is a promising and relevant area of medical chemistry [24][25][26][27]. A number of copper/Disulfiram-based drug combinations are in recruiting clinical trials as inexpensive and highly effective antitumor agents for metastatic breast cancer therapy and as diagnostic tools [28].…”