Vandana Rathore

Synthesis and evaluation of 3-amino/guanidine substituted phenyl oxazoles as a novel class of LSD1 inhibitors with anti-proliferative properties

A series of functionalized phenyl oxazole derivatives was designed, synthesized and screened in vitro for their activities against LSD1 and for effects on viability of cervical and breast cancer cells, and in vivo for effects using zebrafish embryos. These compounds are likely to act via multiple epigenetic mechanisms specific to cancer cells including LSD1 inhibition.

Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents.

A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 4l showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory-antibacterial agent in the present study.

Design, synthesis and molecular modelling studies of novel 3-acetamido-4-methyl benzoic acid derivatives as inhibitors of protein tyrosine phosphatase 1B.

A novel series of 3-acetamido-4-methyl benzoic acid derivatives designed on the basis of vHTS hit ZINC02765569 were synthesized and screened for PTP1B inhibitory activity. The most potent compounds 3-(1-(5-methoxy-1H-benzo[d]imidazol-2-ylthio)acetamido)-4-methyl benzoic acid (10c, IC₅₀ 8.2 μM) and 3-(2-(benzo[d]thiazol-2-ylthio)acetamido)-4-methyl benzoic acid (10e, IC₅₀ 8.3 μM) showed maximum PTP1B inhibitory activity. Docking studies were also performed to understand the nature of interactions governing the binding mode of the designed molecules within the active site of the PTP1B enzyme.

Design, synthesis and biological evaluation of novel arylidine-malononitrile derivatives as non-carboxylic inhibitors of protein tyrosine phosphatase 1B

In this study, we describe the design, synthesis, biological evaluation and molecular modelling studies of novel non-carboxylic arylidine malononitrile-based molecules as Protein Tyrosine Phosphatase 1B (PTP1B) inhibitors. The synthesized derivatives were evaluated in vitro for glucose reuptake using L6 muscle cell lines and enzymatic assay against PTP1B. The biological activity results showed that the 2-methoxy substituted (14b) compound exhibited significant activity in both the assays. The unsubstituted compound (14a) also possessed comparable activity on glucose reuptake in L6 muscle cell lines and better inhibitory activity on PTP1B enzyme assays. Docking analysis was performed on the most potent compound of the series to understand the nature of interactions governing the binding of the designed molecule with the PTP1B enzyme.

Construction of phenoxazine rings containing nitro and sulfonic acid groups leading to phenoxazine-3-sulfonamide derivatives: their evaluation as novel and potential insulin secretagogues

A series of N-(alkyl/aryl/heteroaryl)-1-nitro-10H-phenoxazine-3-sulfonamides was designed, synthesized and evaluated for its hypoglycemic, hyperglycemic and oral anti-diabetic activities. These compounds were prepared via the construction of a phenoxazine ring containing nitro and sulfonic acid groups in a single step followed by further transformations. One of these compounds exhibited promising anti-diabetic activities comparable to glibenclamide and increased serum insulin levels indicating its potential as a novel insulin secretagogue.

In vitro screening of dry fruit extracts of Piper attenuatum for antioxidant and anticancer activity

Indian traditional medicinal plant Piper attenuatum (Buch-Ham) has been investigated for its antioxidant and anticancer activity. Three extracts were prepared using ethyl acetate, ethanol and methanol. In vitro antioxidant activity was performed by ABTS {2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)} free radical scavenging method. All three extracts reduced the free radicals produced by ABTS in a concentration-dependent manner which could be compared to the standard (gallic acid). Invitro anticancer activity of all extracts was carried out by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay method against MCF7 (Michigan Cancer Foundation-7) cell lines. None of the extract showed anticancer activity when compared with the standard (mitomycin C) indicating that P. attenuatum is deprived of antiproliferative or cytotoxic components.

2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents

In this study we examined the suitability of the 3H-imidazo[4,5-b]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives retrieved from our in-house database were evaluated for their cytotoxic activity against nine cancer cell lines. The results indicated that the compounds showed moderate cytotoxic activity against MCF-7, MDA-MB-468, K562 and SaOS2 cells, with K562 being the most sensitive among the four cancer cell lines. The eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity in vitro. The results showed that compound 3f exhibited 2-fold selectivity with IC50 values of 9.2 and 21.8 µmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compound 3f revealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme.

Self-assembled horseshoe type shape transitions in morphology of Cu substituted ZnO

Cu doped ZnO thin films are prepared by the Spray Pyrolysis Technique (SPT) on glass substrate. XRD analysis shows that the films are polycrystalline with hexagonal structure. Intensity of (002) peak is highest indicating a c-axis oriented grains in pure ZnO film. The crystallite size reduces and strain increases with Cu incorporation in the direction of c-axis. AFM images indicate that the grains are self-assembled in the horseshoe type ring shape. At higher doping these rings are totally converted into small grains. Optical band gap decreases from 3.28 eV (pure ZnO film) to 3.25 eV (3% Cu doped ZnO film) and increases further with Cu incorporation. This may be attributed to the presence of excitons in the system.Cu doped ZnO thin films are prepared by the Spray Pyrolysis Technique (SPT) on glass substrate. XRD analysis shows that the films are polycrystalline with hexagonal structure. Intensity of (002) peak is highest indicating a c-axis oriented grains in pure ZnO film. The crystallite size reduces and strain increases with Cu incorporation in the direction of c-axis. AFM images indicate that the grains are self-assembled in the horseshoe type ring shape. At higher doping these rings are totally converted into small grains. Optical band gap decreases from 3.28 eV (pure ZnO film) to 3.25 eV (3% Cu doped ZnO film) and increases further with Cu incorporation. This may be attributed to the presence of excitons in the system.

Flow rate effect on surface morphology of Cu doped CdS thin film by spray pyrolysis technique

Cadmium sulfide (CdS) is a potential material whose functional properties can be tuned by introducing nano-structuring. Here we report the results of flow rate variation in spray technique where in Cu (1%) doped thin film was prepared with varying flow rate of deposited precursor solution. CdS thin film sets in many nano features like grains, nano-rods etc. XRD and AFM techniques are used for the analysis of film morphology. There is a systematic change is morphology which can be explained in the light of models pertaining to the Ostwald ripening.