title: Enantiomeric fluoro-substituted benzothiazole Schiff base-valine Cu(II)/Zn(II) complexes as chemotherapeutic agents: DNA binding profile, cleavage activity, MTT assay and cell imaging studies.
abstract: To evaluate the biological preference of chiral drugs toward DNA target, new metal-based chemotherapeutic agents of Cu(II) and Zn(II), l-/d-fluorobenzothiazole Schiff base-valine complexes 1 &2 (a and b), respectively were synthesized and thoroughly characterized. Preliminary in vitro DNA binding studies of ligand L and complexes 1 &2 (a and b) were carried out in Tris-HCl buffer at pH 7.2 to demonstrate the chiral preference of l-enantiomeric complexes over the d-analogues. The extent of DNA binding propensity was ascertained quantitatively by Kb, K and Ksv values which revealed greater binding propensity by l-enantiomeric Cu(II) complex 1a and its potency to act as a chemotherapeutic agent. The cleavage studies with pBR322 plasmid DNA revealed higher nuclease activity of 1a as compared to 2avia hydrolytic cleavage mechanism. The complexes 1 &2 (a and b) were also screened for antimicrobial activity which demonstrated significantly good activity for l-enantiomeric complexes. Furthermore, cytotoxicity of the complexes 1a and 1b was evaluated by the MTT assay on human HeLa cancer cell line which implicated that more than 50% cells were viable at 15μM. These results were further validated by cell imaging studies which demonstrated the nuclear blebbing.
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Rahman
authors.initials: R
authors.lastname: Alizadeh
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Imtiyaz
authors.initials: I
authors.lastname: Yousuf
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Afzal
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, Aligarh Muslim University, Aligarh 202002, India. Electronic address: farukh_arjmand@yahoo.co.in.
authors.forename: Farukh
authors.initials: F
authors.lastname: Arjmand
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D052160:Benzothiazoles / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects; D002417:Cattle; D003124:Colorimetry; D003300:Copper / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004996:Ethidium / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D062105:Molecular Docking Simulation; D057054:Molecular Imaging; D009690:Nucleic Acid Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012545:Schiff Bases / Q000737:chemistry; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D012545:Schiff Bases; D003300:Copper; D004247:DNA; D004996:Ethidium; C005465:benzothiazole; D015032:Zinc