Design, synthesis, pharmacological evaluation and DNA interaction studies of binuclear Pt(II) complexes with pyrazolo[1,5‐a]pyrimidine scaffold

Abstract

Substituted pyrazolo[1,5‐a]pyrimidine ligands were synthesized by cyclization, using 3‐(thiophen‐2‐yl)‐1H‐pyrazol‐5‐amine with substituted enones (3‐phenyl‐1‐(pyridin‐2‐yl)prop‐2‐en‐1‐one) in presence of KOH and DMF as solvent to form cyclic aromatic compounds. The substituted pyrazolo[1,5‐a] pyrimidine based binuclear PtII complexes containing neutral tetradentated ligands have general formula [Pt2(5a–5f)Cl4], (where, (5a ‐5f) = pyrazolo[1,5‐a] pyrimidine ligand). This compounds were characterized by physicochemical and spectroscopic method like elemental analyses, UV‐Visible, FT‐IR, EDX, TGA, molar conductivity, magnetic susceptibility measurements, mass spectroscopy, 1H and 13C NMR method. The square planar geometry was predicted by electronic spectral study. All PtII compounds were evaluated by antimicrobial assay, in vitro brine shrimp assay, in vivo cellular level bioassay using S. Pombe cells and anti‐tuberculosis study. LC50 (50% lethal concentration) values of compounds are observed between 6.450 ‐ 102.07 μg/mL. UV‐vis absorption titration, competitive displacement assay, molecular docking and viscosity measurement were carried out to examine the binding type and binding strength of complexes. The binding studies suggest partial intercalative binding mode of the complexes and the observed binding constant (Kb) values are found in the order of 6d > 6b > 6c > 6a > 6e > 6 f. The anti‐proliferative cytotoxicity of the synthesized PtII complexes (6a‐6f) were tested against the HCT‐116 (Human Colorectal Carcinoma) cancer cell line.