title: Nuclear blebbing of biologically active organoselenium compound towards human cervical cancer cell (HeLa): in vitro DNA/HSA binding, cleavage and cell imaging studies.
abstract: New pharmacophore organoselenium compound (1) was designed, synthesized and characterized by various spectroscopic methods (IR, ESI-MS, (1)H, (13)C and (77)Se 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.
authors.affiliation: Department of Chemistry, University of Kashmir, Hazratbal, Srinagar, 190006, J&K, India.
authors.forename: Masood Ahmad
authors.initials: MA
authors.lastname: Rizvi
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh, 202002, UP, India.
authors.forename: Mehvash
authors.initials: M
authors.lastname: Zaki
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh, 202002, UP, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Afzal
authors.affiliation: Centre for Material Characterization, CSIR National Chemical Laboratory (NCL), Pune, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Mane
authors.affiliation: Natural Product Microbes, CSIR-Indian Institute of Integrative Medicine (IIIM), Jammu Tawi, 180001, J&K, India.
authors.forename: Manjeet
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Natural Product Microbes, CSIR-Indian Institute of Integrative Medicine (IIIM), Jammu Tawi, 180001, J&K, India.
authors.forename: Bhahwal Ali
authors.initials: BA
authors.lastname: Shah
authors.affiliation: Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Srivastav
authors.affiliation: Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Saripella
authors.initials: S
authors.lastname: Srikrishna
authors.affiliation: Department of Chemistry, University of Kashmir, Hazratbal, Srinagar, 190006, J&K, India.
authors.forename: Ghulam Mustafa
authors.initials: GM
authors.lastname: Peerzada
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh, 202002, UP, India. Electronic address: tsartaj62@yahoo.com.
authors.forename: Sartaj
authors.initials: S
authors.lastname: Tabassum
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D018360:Crystallography, X-Ray; D053837:DNA Cleavage; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D012709:Serum Albumin / Q000737:chemistry*; D013329:Structure-Activity Relationship; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*
chemical_list: D004273:DNA, Neoplasm; D016566:Organoselenium Compounds; D012709:Serum Albumin
keywords: DFT studies; DNA binding; GPx activity; Organoselenium compound; X–ray crystallography; pBR322 hydrolytic cleavage