Design and synthesis of new Zn(II) nalidixic acid-DACH based Topo-II inhibiting molecular entity: Chemotherapeutic potential validated by its in vitro binding profile, pBR322 cleavage activity and molecular docking studies with \DNA\ and \RNA\ molecular targets

Farukh Arjmand (1) , Imtiyaz Yousuf (1) , Mohd. Afzal (1) , Loic Toupet (2)

1 Department of Chemistry
2 GMCM - Groupe matière condensée et matériaux

Nalidixic acid-DACH based Zn(II) molecular entity (1) was synthesized and thoroughly characterized by spectroscopic techniques (FT-IR, 1H and 13C NMR, ESI-MS) and single crystal X-ray crystallography as a potential chemotherapeutic drug candidate. The comparative in vitro binding studies of complex 1 with targets like CT-DNA and yeast tRNA were carried out by employing UV-vis, emission spectroscopy, circular dichorism and viscosity which revealed higher binding affinity of 1 towards yeast tRNA as compared to CT-DNA. Complex 1 cleaves pBR322 plasmid via hydrolytic pathway (validated by \T4\ religation assay); in addition, 1 also exhibited significant inhibitory effects on the catalytic activity of Topo-II at a concentration of 30 μM. Further, validation of the interaction studies was accompolished by carrying out molecular docking studies with DNA, \RNA\ and Topo-II targets. This work also advances our knowledge for the development and design of small \RNA\ targeted therapeutic molecules which were relatively under exploited drug targets.

Mots clés: Molecular docking

Domaines: Chimie inorganique

Farukh Arjmand, Imtiyaz Yousuf, Mohd. Afzal, Loic Toupet. Design and synthesis of new Zn(II) nalidixic acid-DACH based Topo-II inhibiting molecular entity: Chemotherapeutic potential validated by its in vitro binding profile, pBR322 cleavage activity and molecular docking studies with \DNA\ and \RNA\ molecular targets. Inorganica Chimica Acta, 2014, 421, pp.26-37. ⟨10.1016/j.ica.2014.05.015⟩. ⟨hal-01004611⟩