Synthesis and crystal structure elucidation of new copper(II)-based chemotherapeutic agent coupled with 1,2-DACH and orthovanillin: Validated by in vitro DNA/HSA binding profile and pBR322 cleavage pathway.
New copper(II)-based complex (1) was synthesized and characterized by analytical, spectroscopic and single crystal X-ray diffraction. The in vitro binding studies of complex 1 with CT DNA and HSA have been investigated by employing biophysical techniques to examine the binding propensity of 1 towards DNA and HSA. The results showed that 1 avidly binds to CT DNA via electrostatic mode along with the hydrogen bonding interaction of NH2 and CN groups of Schiff base ligand with the base pairs of DNA helix, leads to partial unwinding and destabilization of the DNA double helix. Moreover, the CD spectral studies revealed that complex 1 binds through groove binding interaction that stabilizes the right-handed B-form of DNA. Complex 1 showed an impressive photoinduced nuclease activity generating single-strand breaks in comparison with the DNA cleavage activity in presence of visible light. The mechanistic investigation revealed the efficiency of 1 to cleave DNA strands by involving the generation of reactive oxygen species. Furthermore, the time dependent DNA cleavage activity showed that there was gradual increase in the amount of NC DNA on increasing the photoexposure time. However, the interaction of 1 and HSA showed that the change of intrinsic fluorescence intensity of HSA was induced by the microenvironment of Trp residue.
Department of Chemistry, Aligarh Muslim University, Aligarh, UP 202002, India.
Mehvash
M
Zaki
Department of Chemistry, Aligarh Muslim University, Aligarh, UP 202002, India.
Mohd
M
Afzal
Department of Applied Chemistry, Aligarh Muslim University, Aligarh, UP 202002, India.
Musheer
M
Ahmad
Department of Chemistry, Aligarh Muslim University, Aligarh, UP 202002, India. Electronic address: tsartaj62@yahoo.com.
Sartaj
S
Tabassum
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism; D001547:Benzaldehydes / Q000737:chemistry; D002417:Cattle; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000378:metabolism; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003514:Cyclohexylamines / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053837:DNA Cleavage / Q000528:radiation effects; D006801:Humans; D008024:Ligands; D008027:Light; D008968:Molecular Conformation; D010957:Plasmids / Q000378:metabolism*; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism; D012545:Schiff Bases / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013055:Spectrophotometry, Infrared; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D001547:Benzaldehydes; D056831:Coordination Complexes; D003514:Cyclohexylamines; D008024:Ligands; D017382:Reactive Oxygen Species; D012545:Schiff Bases; D012709:Serum Albumin; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; C030435:1,2-cyclohexanediamine; C100058:vanillin
HSA binding; In vitro DNA binding; Photoinduced DNA cleavage; X-ray crystallography