Karthik Dhananjayan

ABSTRACT Terpenoids and flavonoids were evaluated for Acetylcholinesterase inhibition using in-silico and in-vitro methods. Insilico docking method is carried out using AutoDock 4.2 tools and in-vitro AChE inhibition was based on Ellman method. The protein structure (amino acid sequence)of human AChE is similar to AChE from electric eelwas used for the evaluation. The crystal structure of AChE was downloaded from RCSB protein data bank. Terpenoids used for docking study were Ambrein, Geraniol, Limonene. Linalool, and ferulic acid whose lowest binding energy(kcal/mol) was found to be -9.54 kcal/mol, - 5.22 kcal/mol, -5.46 kcal/mol, -5.16 kcal/mol, -5.17 kcal/mol and their supporting IC50 values obtained through in-vitro enzyme inhibition studies were 91 µg/ml ± 0.12, 200 µg/ml ± 0.21, 195 µg/ml ± 0.43, 200 µg/ml ± 0.24, 185 µg/ml ± 0.56 respectively. Flavonoids used for the docking studies were Quercetin, Curcumin, Myricetin, Kaempferol, and Luteolin whoselowest binding energy was found to be -8.34kcal/mol, -8.21 kcal/mol, -8.28 kcal/mol,-7.16 kcal/mol and -8.56 kcal/mol respectively. Tacrine was used as a standard and its lowest binding energy was found to be -7.17 kcal/mol and its corresponding IC50 value was found to be 155 µg/ml ± 0.11. This study revealed the acetylcholine esterase inhibition potential of different commercially available terpenoids and flavonoids.

The ethanolic extracts of Pergularia daemia (Forsk.) was evaluated for its gastro-protective function on ethanol induced ulcer in albino rats. The leaves of Pergularia daemia was subjected to continuous hot percolation process. The acute toxicity studies revealed that LD50> 2000mg/kg for the extract. Pergularia daemia (Forsk) showed a dose dependent curative ratio compared to ulcer control groups. The values are statistically significant at two levels p<0.001, p<0.01. The EEPD exhibits antiulcer activity, which could be due to the presence of saponins or sugar-free polyphenols, and, thus, confirmed the traditional uses of Pergularia daemia (Forsk.) in the treatment of ulcers

Terpenoids and flavonoids were evaluated for Acetylcholinesterase inhibition using in-silico and in-vitro methods. Insilico docking method is carried out using AutoDock 4.2 tools and in-vitro AChE inhibition was based on Ellman method. The protein structure (amino acid sequence)of human AChE is similar to AChE from electric eelwas used for the evaluation. The crystal structure of AChE was downloaded from RCSB protein data bank. Terpenoids used for docking study were Ambrein, Geraniol, Limonene. Linalool, and ferulic acid whose lowest binding energy(kcal/mol) was found to be -9.54 kcal/mol, - 5.22 kcal/mol, -5.46 kcal/mol, -5.16 kcal/mol, -5.17 kcal/mol and their supporting IC50 values obtained through in-vitro enzyme inhibition studies were 91 µg/ml ± 0.12, 200 µg/ml ± 0.21, 195 µg/ml ± 0.43, 200 µg/ml ± 0.24, 185 µg/ml ± 0.56 respectively. Flavonoids used for the docking studies were Quercetin, Curcumin, Myricetin, Kaempferol, and Luteolin whoselowest binding energy was found to be...

The purpose of present study was to investigate the methanolic bark extract of Hymenodictyon excelsum (Roxb) Wall for its apoptosis, cytotoxic activities. Induction of apoptosis was carried out on L-929 cell line. The cytotoxic activity was evaluated by MTT assay against lung fibroblast (L-929) cell line and trypan blue dye exclusion assay on dalton’s lymphoma ascites (DLA) cells. Morphological changes and DNA fragmentation were found upon incubation with extract. The extract was found to be cytotoxic towards L-929 cells in 72 h MTT assay and concentration required for 50% cell death was 3.85µg/ml. Thus from the present investigation it can be concluded that the methanolic bark extract of Hymenodictyon excelsum (Roxb) exhibited apoptosis induction and cytotoxic activities

Docking evaluations and accuracy of results are based on the scoring function utilized by softwares. MoleGro Virtual Docker 6.0, utilizes MolDock scoring function, a modified piecewise linear potential scoring method. Some selective bio-flavonoids were investigated for its activity against BACE-1. The ligands were designed computationally and their geometry has been optimized using MOPAC. Those energy minimized ligands were docked against the crystal structure of BACE1. Mostof the polyphenolic compounds used for evaluation showed mol dock score range between -20.00 to -148.00 kj/mol. When comparing with the reference standard, these ligands showed better binding affinity. Binding site analysis also revealed the access of ligands on active site of the enzyme with high fidelity.

Kinase suppressor of Ras-1 (KSR1) is a conserved component of the Ras pathway that acts as a molecularscaffold to promote signal transmission from Raf-1 to MEK and MAPK. All KSR-1 proteins contain a conserved cysteinerich C1 domain, and studies have implicated this domain in the regulation of KSR-1 sub cellular localization and function. In this study an evaluation on binding affinity of coumarin and anthraquinone derivatives on crystal structure of C1 domain of kinase suppressor of RAS was carried out using docking studies. Study showed the occupancy and importance of certain functional groups at the anthraquinone and coumarin nucleus responsible for its potential affinity in binding. These ligands can serve as a lead moiety in developing a targeted drug against the kinase suppressor of ras-1 to interrupt MAPK signaling in neoplasia

Some selective polyphenolics was designed computationally and screened through insilico docking studies against crystal structure of Dipeptidylpeptidase-IV (DPP-IV) as a projected target for Type 2 Diabetes Mellitus. Insilico docking (rigid and flexible) methodology using Auto Dock 4.2 comprising a search method Genetic Lamarckian algorithm was used. Genetic Lamarckian algorithm performs an Automated Docking and has an advantage of empirical binding free energy force field that allows the prediction of binding free energies, and hence binding constants, for docked ligands. In-silico evaluationshows satisfactory docking results, when compared with standard using rigid and as well as flexible docking It is concluded that investigational ligands has the potential of inhibiting DPP-IV and there by further screening (invitro and invivo) studies can be carried out in order to findout optimized bioflavonoids for treating type2diabetes mellitus.

Polyphenolic compounds posses vast number of biological activities and they are the inclusions of phytoconstituents of plant kingdom. Synthetic drugs usedin the treatment of neurodegenerative disorders like Alzheimer’s disease is of only symptomatic and for not permanent cure over the progression of the disease. Beta secretase-1(BACE1) is aspartic protease makes improper cleavage of amyloid precursor protein (APP) found on the membrane of the neuronal cells and produces the accumulation of beta amyloid proteins of insoluble fractions. Polyphenolic compounds like catechin3gallate, hesperidin, hesperitin etc., were found to possess lowest binding energy with best conformation, when comparing with the standard reference ligands. In this insilico docking studies, it revealed that targeting BACE1 inhibition, through Polyphenolic compounds can create number of lead molecules for better therapeutic concern in future

Kinase Suppressor of Ras (KSR) is a molecular scaffold that interacts with the core kinase components of the ERK cascade, Raf, MEK, ERK to provide spatial and temporal regulation of Ras-dependent ERK cascade signaling. Interruption of this mechanism can have a high influence in inhibiting the downstream signaling of the mutated tyrosine kinase receptor kinase upon ligand binding. Still none of the studies targeted to prevent the binding of Raf, MEK binding on kinase suppressor of RAS. In that perspective the cysteine rich C1 domain of scaffold proteins kinase suppressor of Ras-1 was targeted rather than its ATP binding site with small ligand molecules like flavones and anthocyanidins and analyzed through insilico docking studies. The binding energy evaluation shows the importance of hydroxyl groups at various positions on the flavone and anthocyanidin nucleus. Over all binding interaction shows these ligands occupied the potential sites of cysteine rich C1 domain of scaffold protein...

Rho Kinases regulate a wide range of biological
processes, including reorganization of the actin cytoskeleton,
transcriptional regulation, vesicle trafficking, morphogenesis,
neutrophil activation, phagocytosis and activation of the
NADPH oxidase, mitogenesis, apoptosis and tumorigenesis.
Rho associated coiled coil kinase-II (ROCK-II) is one of the
isoform of Rho associated coiled coil kinase. ROCK-II is
distributed mostly in the brain and heart.Insilico docking
studies was carried out in targeting the crystal structure of
ROCK-II with some rare selective flavonoids. Fasudil, well
known ROCK-II inhibitor was used as a reference ligand.
Amentoflavone and some selective flavonoids were showed
lowest binding energy with corresponding dissociation constant (kd) values on comparing with reference ligands. It has
been found out that these compounds possess inhibitory activity against ROCK-II through computational analysis.