title: Structure dependent selective efficacy of pyridine and pyrrole based Cu(II) Schiff base complexes towards in vitro cytotoxicity, apoptosis and DNA-bases binding in ground and excited state.
abstract: This work highlights a systematic and comparative study of the structure-dependent influence of a series of biologically active Cu(II) Schiff base complexes (CSCs) on their in vitro cytotoxicity, apoptosis and binding with polymeric DNA-bases in ground and photo-excited states. The structure-activity relationship of the closely resembled CSCs towards in vitro cytotoxicity and apoptosis against cervical cancerous HeLa and normal human diploid WI-38 cell lines has been investigated by MTT assay and FACS techniques respectively. The steady-state and time-resolved spectroscopic studies have also been carried out to explore the selective binding affinities of the potential complexes towards different polymeric nucleic acid bases (poly d(A), poly d(T), poly d(G), poly d(C), Poly d(G)-Poly d(C)), which enlighten the knowledge regarding their ability in controlling the structure and medium dependent interactions in 'ground' and 'excited' states. The pyridine containing water soluble complexes (CuL(1) and CuL(3)) are much more cytotoxic than the corresponding pyrrole counterparts (CuL(2) and CuL(4)). Moreover the acidic hydrogens in CuL(1) increase its cytotoxicity much more than methyl substitution as in CuL(3). The results of MTT assay and double staining FACS experiments indicate selective inhibition of cell growth (cell viability 39% (HeLa) versus 85% (WI-38)) and occurrence of apoptosis rather than necrosis. The ground state binding of CuL(1) with polymeric DNA bases, especially with guanine rich DNA (Kb=6.41±0.122×10(5)), that enhances its cytotoxic activity, is further confirmed from its binding isotherms. On the other hand the pyrrole substituted CuL(4) complex exhibits the structure and medium dependent selective electron-transfer in triplet state as observed in laser flash photolysis studies followed by magnetic field (MF) effect.
authors.affiliation: Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
authors.forename: Banabithi
authors.initials: B
authors.lastname: Koley Seth
authors.affiliation: Crystallography and Molecular Biology, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
authors.forename: Arpita
authors.initials: A
authors.lastname: Saha
authors.affiliation: Biophysics and Structural Genomics, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
authors.forename: Srijan
authors.initials: S
authors.lastname: Haldar
authors.affiliation: Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
authors.forename: Partha Pratim
authors.initials: PP
authors.lastname: Chakraborty
authors.affiliation: Crystallography and Molecular Biology, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
authors.forename: Partha
authors.initials: P
authors.lastname: Saha
authors.affiliation: Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India. Electronic address: samita.basu@saha.ac.in.
authors.forename: Samita
authors.initials: S
authors.lastname: Basu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010782:Photolysis; D011725:Pyridines / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D012545:Schiff Bases / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011725:Pyridines; D011758:Pyrroles; D012545:Schiff Bases; D003300:Copper; D004247:DNA
keywords: Binding isotherm; FACS; Laser flash photolysis; MTT assay; Magnetic field effect; UV–Vis