Biophysical binding profile with ct-DNA and cytotoxic studies of a modulated nanoconjugate of umbelliferone cobalt oxide loaded on graphene oxide (GO) as drug carrier.

In an attempt to identify suitable nano-carriers for drug delivery, natural drug umbelliferone was chosen to synthesize new modulated nanoconjugate of umbelliferone cobalt oxide with cobalt (II) nitrate in one pot assembly in the presence of tannic acid. The synthesized nanoconjugate drug (NCD) was then loaded on graphene oxide (GO) as drug carrier by simple ultrasonication method and thoroughly characterized by various spectroscopic techniques (FT-IR, SEM, TEM, XRD, EPR and thermogravimetric analysis) which revealed the successful loading of the nanoconjugate drug on GO. The UV-visible, fluorescence and electrochemical studies suggested that strong π-π stacking interactions exist between nanoconjugate drug and GO. The binding studies of NCD-GO with ct-DNA were performed by various optical and biophysical methods viz., UV-visible, fluorescence, circular dichroism (CD) and cyclic voltammetry (CV) which indicated electrostatic mode of binding towards the ct-DNA. Furthermore, condensate of nanoconjugate drug-loaded GO (NCD-GO) with ct-DNA was prepared and analyzed by scanning electron microscopy (SEM) which revealed that the interaction of NCD-GO with ct-DNA had occurred. Cleavage activity of NCD-GO with pBR322 was evaluated by gel electrophoresis and it was found that NCD-GO cleave DNA through hydrolytic pathway involving hydroxyl radical (OH). The cytotoxicity of NCD-GO was evaluated against human liver carcinoma (Huh-7), prostate cancer (Du-145) cell lines along with normal cell line (PNT 2). The results obtained showed selective cytotoxic activity of NCD-GO against Du-145 cell lines. The intracellular uptake was visualized by confocal microscopy which revealed the significant cellular uptake and internalization of nanoparticles by cells. Moreover, the adsorption of cobalt oxide umbelliferone on GO was studied by density functional theory. The process of adsorption was found exothermic in nature and the optimized geometry structure is quite stable. Communicated by Ramaswamy H. Sarma.

New Tailored RNA-Targeted Organometallic Drug Candidates against Huh7 (Liver) and Du145 (Prostate) Cancer Cell Lines.

New organometallic drug candidates [Ph2Sn(HL)], 1, and [Ru(η6--p-cymene)(HL)Cl], 2, were designed and synthesized by in situ reaction of a Schiff base ligand (HL) and diphenyltin dichloride and [RuCl2(p-cymene)]2, respectively. The drug candidates 1 and 2 have been characterized by spectroscopic methods (Fourier-transform infrared spectroscopy, UV-vis, and 1H/13C NMR), elemental analysis, and single X-ray crystallographic studies (in case of 1). The ground-state geometry optimization of 1 and 2 was performed by density functional theory calculations. The interaction of 1 and 2 with tRNA was assessed by absorption spectroscopy, cyclic voltammetry, circular dichroism, and ethidium bromide displacement assay using fluorescence emission spectroscopy to determine their potential to act as antitumor agents. The cytotoxicity of 1 and 2 was screened against human liver carcinoma (Huh7), prostate cancer (Du145), and the normal prostate cell line (PNT 2). The results implicated a dose-dependent growth inhibition of the two cancer cells at concentrations (2.5-15 µM) of 1 and 2 with the treatment after 48 h. Interestingly, 1 revealed good selective activity toward the liver cancer cell line (Huh7). Furthermore, both the drug candidates 1 and 2 were found to be nontoxic toward the PNT 2 normal cell line. These studies lay a paradigm for rational efficacious drug design for chemotherapeutic intervention in cancers using new tailored organometallic drug entities; organotin(IV) and organoruthenium(II) have been demonstrated to be viable for the safe administration and specific targeted drug uptake by the resistant cancerous cell lines at low intracellular concentrations.