Response of Ancillary Azide Ligand in Designing a 1D Copper(II) Polymeric Complex along with the Introduction of High DNA- and HAS-Binding Efficacy, Leading to Impressive Anticancer Activity: A Compact Experimental and Theoretical Approach

Abstract

A new versatile azide-bridged polymeric Cu(II) complex, namely, [Cu(L)(μ 1,3 -N 3 )] ∞ ( 1 ), was synthesized utilizing an N,N,O-donor piperidine-based Schiff base ligand ( E )-4-bromo-2-((2-(-1-yl)imino)methyl)phenol ( HL ), obtained via the condensation reaction of 1-(2-aminoethyl) piperidine and 5-bromo salicylaldehyde. The single-crystal X-ray diffraction analysis reveals that complex 1 consists of an end-to-end azido-bridged polymeric network, which is further rationalized with the help of a density functional theory (DFT) study. After routine characterization with a range of physicochemical studies, complex 1 is exploited to evaluate its biomedical potential. Initially, theoretical inspection with the help of a molecular docking study indicated the ability of complex 1 to effectively bind with macromolecules such as DNA and the human serum albumin (HSA) protein. The theoretical aspect was further verified by adopting several spectroscopic techniques. The electronic absorption spectroscopic analysis indicates a remarkable binding efficiency of Complex 1 with both DNA and HSA. The notable fluorescence intensity reduction of the ethidium bromide (EtBr)–DNA adduct, 4′,6-diamidino-2-phenylindole (DAPI)–DNA adduct, and HSA after the gradual addition of complex 1 authenticates its promising binding potential with the macromolecules. The retention of the canonical B form of DNA and α form of HSA during the association of complex 1 was confirmed by implementing a circular dichroism spectral study. The association ability of complex 1 with macromolecules further inspired us to inspect its impact on different cell lines such as HeLa (cervical cancer cell), PA1 (ovarian cancer cell), and HEK (normal cell). The dose-dependent and time-dependent in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay suggests an effective antiproliferative property of complex 1 with low toxicity toward the normal cell line. Finally, the anticancer activity of complex 1 toward carcinoma cell lines was analyzed by nuclear and cellular staining techniques, unveiling the cell death mechanism.

A multi-spectroscopic and molecular docking approach for DNA/protein binding study and cell viability assay of first-time reported pendent azide bearing Cu(II)-quercetin and dicyanamide bearing Zn(II)-quercetin complexes

“…It's interesting to note that it is a well-known anticancer agent and that its mechanism of cell death is also disclosed [ 24 , 25 ]. The use of cisplatin as an effective anticancer drug, inspires the scientific community to develop several metal-based compounds with effective biological applications [ [26] , [27] , [28] , [29] , [30] , [31] , [32] ]. At the same time, many quercetin-metal complexes are synthesized and inspected with respect to their DNA and HSA binding efficacy [ [33] , [34] , [35] , [36] ].…”

“…At the same time, many quercetin-metal complexes are synthesized and inspected with respect to their DNA and HSA binding efficacy [ [33] , [34] , [35] , [36] ]. But no literature report is obtained where the quercetin-metal complex with one ancillary ligand has been developed, although it is well established that the presence of ancillary ligands like azide, thiocyanate, and dicyanamide in the metal center enhances the DNA/HSA binding efficacy [ [37] , [38] , [39] , [40] ], Therefore, it is reasonable to anticipate that the addition of an ancillary ligand will improve the ability of quercetin metal complexes to bind with macromolecules (see Scheme 1 ).

Scheme 1 Synthesis of complex 1 and 2 .

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DNA/Protein Binding and Apoptotic-Induced Anticancer Property of a First Time Reported Quercetin–Iron(III) Complex Having a Secondary Anionic Residue: A Combined Experimental and Theoretical Approach

“…Among cancer-preventive medications, flavonoids have received the most research attention. It is undeniably true that these substances can impede some particular stages of the carcinogenic process by reducing cell growth and inducing apoptosis in a variety of cancer cell types. − The anticancer effects of flavonoids may be explained by their antioxidant capacity, which typically occurs via suppression of reactive oxygen species production. − Apples, red grapes, onions, raspberries, honey, cherries, citrus fruits, and green leafy vegetables are all sources of the well-known flavonoid quercetin (3,3′,4′,5,7 pentahydroxyflavone), which has a well-established efficacy against cancer-related diseases via several targeted pathways. − Chemists began to believe that a metal–organic complex might demonstrate efficient anticancer properties like other organic anticancer medication molecules after the successful development of cisplatin as an anticancer medicine. The widespread usage of this great medicine is somewhat constrained by the numerous negative effects of cisplatin.…”

“…10 − 12 Apples, red grapes, onions, raspberries, honey, cherries, citrus fruits, and green leafy vegetables are all sources of the well-known flavonoid quercetin (3,3′,4′,5,7 pentahydroxyflavone), which has a well-established efficacy against cancer-related diseases via several targeted pathways. 13 − 15 Chemists began to believe that a metal–organic complex might demonstrate efficient anticancer properties like other organic anticancer medication molecules after the successful development of cisplatin as an anticancer medicine. The widespread usage of this great medicine is somewhat constrained by the numerous negative effects of cisplatin.…”