Y. Pavan Kumar

Diffusion and Birefringence of Bioactive Dyes in a Supramolecular Guanosine Hydrogel

Transparent self-standing supramolecular hydrogels were readily prepared by the potassium-ion-mediated self-organization of guanosine and 8-bromoguanosine whilst the individual components precipitated within a few hours. VT-NMR spectroscopy showed that bromoguanosine was a superior gelator compared to guanosine. XRD analysis showed that gel formation was caused by stacked G-quartets. AFM analysis revealed dendritic architectures of the nanofibers in the two-component hydrogel network. DSC profiles showed that the hybrid hydrogels underwent sol-gel transition at lower temperature than the pure guanosine and bromoguanosine hydrogels. Interestingly, bioactive dyes, such as rose bengal, rhodamine-6-G, and fluorescein, could be diffused and released in a controlled manner. UV/Vis absorption and fluorescence spectroscopy and CLSM were used to investigate the diffusion behavior of dyes in the hydrogel network. These dyes exhibited strong birefringence in the gel network (0.07-0.1) as a result of the anisotropic organization.

A DNA-Inspired Synthetic Ion Channel Based on G–C Base Pairing

A dinucleoside containing guanosine and cytidine at the end groups has been prepared using a modular one-pot azide-alkyne cycloaddition. Single channel analysis showed that this dinucleoside predominantly forms large channels with 2.9 nS conductance for the transport of potassium ions across a phospholipid bilayer. Transmission electron microscopy, atomic force microscopy, and circular dichroism spectroscopy studies reveal that this dinucleoside can spontaneously associate through Watson-Crick canonical H-bonding and π-π stacking to form stable supramolecular nanostructures. Most importantly, the ion channel activity of this G-C dinucleoside can be inhibited using the nucleobase cytosine.

A Fluorescent Guanosine Dinucleoside as a Selective Switch‐On Sensor for c‐myc G‐Quadruplex DNA with Potent Anticancer Activities

Like likes like! A novel fluorescent C2 -symmetric guanosine-based dinucleoside has been engineered by chemical ligation of two guanosine units with a biocompatible dansyl tag. The nucleoside exhibits high selectivity for c-myc G-quadruplex DNA through fluorescence enhancement over duplex DNA and other promoter G-quadruplexes (see scheme). It stains the nucleus preferentially, arrests the cell cycle at the G2/M phase, inhibits cell growth, and induces apoptosis in A375 cancer cells.

Fluorescent Dansyl-Guanosine Conjugates that Bind c-MYC Promoter G-Quadruplex and Downregulate c-MYC Expression.

The four‐stranded G‐quadruplex present in the c‐MYC P1 promoter has been shown to play a pivotal role in the regulation of c‐MYC transcription. Small‐molecule compounds capable of inhibiting the c‐MYC promoter activity by stabilising the c‐MYC G‐quadruplex could potentially be used as anticancer agents. In this context, here we report the synthesis of dansyl‐guanosine conjugates through one‐pot modular click reactions. The dansyl‐guanosine conjugates can selectively detect c‐MYC G‐quadruplex over other biologically relevant quadruplexes and duplex DNA and can be useful as staining reagents for selective visualisation of c‐MYC G‐quadruplex over duplex DNA by gel electrophoresis. NMR spectroscopic titrations revealed the preferential binding sites of these dansyl ligands to the c‐MYC G‐quadruplex. A dual luciferase assay and qRT‐PCR revealed that a dansyl‐bisguanosine ligand represses the c‐MYC expression, possibly by stabilising the c‐MYC G‐quadruplex.

Self-Assembly of a Guanosine Derivative To Form Nanostructures and Transmembrane Channels

We herein report the self-assembly of a lipophilic bromoguanosine derivative (G1) in homogeneous solution, in the solid state and in planar bilayer membranes. The self-assembly of G1, driven by H-bonding and π-π stacking interactions can form different nano-structures depending on incubation time. The G1 nanostructure is able to bind a bioactive dye like Rose Bengal. In crystal state, it shows ribbon type H-bonding pattern and exhibits birefringence in polarized light. And further, the self-assembled nanostructure of G1 can form discrete transmembrane ion channels in lipid bilayer membranes, enabling passage of potassium ions.

In vitro s creening of known drugs identified by scaffold hopping techniques shows promising leishmanicidal activity for suramin and netilmicin

ObjectiveThe rapid emergence of drug resistant Leishmanial strains makes it imperative to continue the development of cheap and effective drugs against the parasite. Due to the absence of effective vaccines against leishmaniasis, current therapeutic measures exclusively rely on chemotherapy. Here we attempt, to identify novel antileishmanial from a list of known drugs determined from a previous bioinformatics study. Synergism between various drug combinations (involving netilmicin, suramin, paromomycin and curcumin) have been estimated to identify potent multidrug therapies to combat the disease.ResultsThe drugs were screened against Leishmania promastigotes by utilizing the MTT assay and against intracellular amastigotes using murine Macrophage like tumor cell, RAW 264.7 as a host. In vitro drug interactions were tested for several drug combinations with a modified fixed ratio isobologram method against both Leishmania major and Leishmania donovani. This work reports the in vitro antileishmanial activity for the aminoglycoside netilmicin (for some Leishmania parasites) and the anti-trypanosomatid suramin. Synergism was also observed between paromomycin–suramin and netilmicin–curcumin.