title: Targeting protein kinase and DNA molecules by diimine-phthalate complexes in antiproliferative activity.
abstract: The serendipitous discovery of the anticancer drug cisplatin cemented medicinal inorganic chemistry as an independent discipline in 1960s. DNA and protein kinases are one of the major intracellular targets of many anticancer drugs. It is thus highly desirable to develop metal complexes, either by interacting with DNA or to target alternative cellular machinery such as protein kinases to provide a more effective means of monitoring disease progression. In this study we report the synthesis and characterization of few novel Cu(II) and Zn(II) Knoevenagel condensed metallointercalators incorporating phthalic acid. The intercalation behavior of the complexes with DNA is confirmed by spectral and analytical experiments. Due to the promising performance of DNA interaction efficacy of Cu(II) complexes 1-4, their in vitro and in vivo anticancer properties are explored on various cancerous cell lines which reveal that they exhibit substantial anticancer activity without affecting the normal cells. It is found that the complex 1 induces apoptosis in Hep G2 cells. Theoretically, DFT is used to optimize the Cu(II) complexes 1-4 to explore their quantum mechanical properties and to carry out affinity studies against cyclin dependant kinase 2 (CDK2) to understand atomic level interactions. Further, the complex-receptor stability is confirmed by molecular dynamics.
authors.affiliation: Research Department of Chemistry, VHNSN College, Virudhunagar 626001, India. Electronic address: pravinknp2012@gmail.com.
authors.forename: Narayanaperumal
authors.initials: N
authors.lastname: Pravin
authors.affiliation: College of Pharmacy, Madras Medical College, Chennai 600003, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Devaraji
authors.affiliation: Research Department of Chemistry, VHNSN College, Virudhunagar 626001, India. Electronic address: ramchem1964@gmail.com.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Raman
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004247:DNA / Q000187:drug effects; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010795:Phthalic Acids / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000187:drug effects; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D010795:Phthalic Acids; C032279:phthalic acid; D003300:Copper; D004247:DNA; D011494:Protein Kinases; D015032:Zinc
keywords: Anticancer activity; Metallointercalators; Molecular docking