Targeting protein kinase and DNA molecules by diimine–phthalate complexes in antiproliferative activity
2015
Pravin, Narayanaperumal | Devaraji, Vinod | Raman, Natarajan
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.
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