Nuclear blebbing of biologically active organoselenium compound towards human cervical cancer cell (HeLa): In vitro DNA/HSA binding, cleavage and cell imaging studies

• New molecular drug candidate was synthesized and characterized.
• DNA/HSA binding studies revealed the electrostatic interaction into the minor groove.
• Compound 1 show single strand cleavage via hydrolytic pathway.
• Molecular docking studies revealed minor groove binding in the GC rich sequences.

New pharmacophore organoselenium compound (1) was designed, synthesized and characterized by various spectroscopic methods (IR, ESI–MS, 1H, 13C and 77Se NMR) and further confirmed by X–ray crystallography. Compound 1 consists of two 3,5–bis(trifluoromethyl)phenyl units which are connected to the selenium atom via the organometallic C–Se bond. In vitro DNA binding studies of 1 was investigated by absorption and emission titration methods which revealed that 1 recognizes the minor groove of DNA in accordance with molecular docking studies with the DNA duplex. Gel electrophoretic assay demonstrates the ability of 1 to cleave pBR322 DNA through hydrolytic process which was further validated by T4 religation assay. To understand the drug–protein interaction of which ultimate molecular target was DNA, the affinity of 1 towards HSA was also investigated by the spectroscopic and molecular modeling techniques which showed hydrophobic interaction in the subdomain IIA of HSA. Furthermore, the intracellular localization of 1 was evidenced by cell imaging studies using HeLa cells.

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