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Articles by N.S. Hari Narayana Moorthy
Total Records ( 7 ) for N.S. Hari Narayana Moorthy
  Ashutosh Jamloki , C. Karthikeyan , S.K. Sharma , N.S. Hari Narayana Moorthy and P. Trivedi
  A quantitative structure-activity relationship study on 6-aryl-pyrazolo (3,4-b) pyridines was performed to gain structural insight into the binding mode of the molecules to the glycogen synthase kinase -3α, an enzyme phosphorylate and inhibit Glycogen Synthase (GS) which is the rate limiting enzyme in the glycogen biosynthesis. The molecular modeling studies were performed using CS Chem. Office 2001 molecular modeling software version 6.0. Allinger`s MM2 force field by fixing Root Mean Square Gradient (RMS) to 0.1 Kcal mol-1 and semiemperical AM1 Hamiltonian method (MOPAC module) were used to minimize the energy and calculate descriptors. The thermodynamic and steric features of 6-aryl-pyrazolo (3,4-b) pyridines are highly correlated with GSK-3α inhibitory activity. The results of the study suggests that introduction of bulky groups at C-5 position of the pyrazolopyridine ring will increase the GSK-3α inhibitory potency as it may involve in hydrophobic interaction with the ATP binding site of the enzyme. The results of the study reveal that the conformational rigidity and orientation of molecule play significant role in the GSK-3α inhibitory activity. Additionally, electronic interactions between molecule and enzyme were found to be crucial for GSK-3α inhibitory activity.
  Vipin Saxena and N.S. Hari Narayana Moorthy
  The Insulin like Growth Factor-1 (IGF-1) receptors are members of the super family of Receptor Tyrosine Kinase (RTKs) implicated in human cancers due to amplification, overexpression or somatic mutation of the gene. The type-1 insulin like growth receptors (IGF-1R) is overexpressed by many tumors and mediates proliferation, motility and apoptosis protection. Tumor growth and metastasis can be blocked by agents that inhibit IGF-1R expression or function, suggesting that the IGF-1R is a promising treatment target. The strategies to block IGF-1R function employed anti-IGF-1R antibodies, small-molecule inhibitors of the IGF-1R tyrosine kinase, antisense oligodeoxynucleotides and antisense RNA, small inhibitory RNA, triple helix, dominant negative mutant and various compounds reducing ligand availability. Studies show that antisense IGF-1R expression in melanoma cells leads to enhanced radio sensitivity and impaired activation of ATM, required for DNA double strand break repair. Antisense and dominant negative strategies also enhance tumor cell chemosensitivity induced by tumor cells and killed in vivo by IGF-1R antisense. However, antisense agents cause only modest IGF-1R down regulation and can affect the insulin receptor. Specificity is an important issue for the development of both kinase inhibitors and molecular reagents. Using an array-based screen to identify accessible region of IGF-1R mRNA, are designed small interfering RNAs (siRNAs) that induce potent IGF-1R gene silencing without affecting the insulin receptor. These siRNAs block IGF-signaling, enhancing radio and chemosensitivity and show a genuine therapeutic potential. The clinical efficacy of IGF-1R targeting will be determined by key factors including the role of receptors in established tumors. The potency of inhibition achieved in vivo and the extent to which other signaling pathways compensate for IGF-1R loss.
  Garvita Chaudhary , C. Karthikeyan , N.S. Hari Narayana Moorthy and Piyush Trivedi
  Quantitative Structure Activity Relationship (QSAR) studies were performed on some tubulin-binding agents. The compounds in the selected series were characterized by topological and Approximate Surface Area descriptors calculated using QuaSAR module of Molecular Operating Environment (MOE). Significant equations were derived from regression analysis shows significance of different descriptors contributing towards the cytotoxic activity. The results of the study show that cytotoxic activity of diarylsulphonylurea can be successfully explained in terms of topology of the molecule. VSA_don contribution towards the activity indicates molecules capable of hydrogen bonding will be beneficial for tubulin polymerization inhibitory activity. Another descriptor contributing beneficially to the cytotoxic action of diarylsulphonylurea is SMR_VSA5. SMR deals with polarizibility; hence increasing polarizibility will increase cytotoxic activity. Negative contribution of a_nN descriptor to the biological activity, signifies that the introduction of nitrogen should be kept minimum while designing new cytotoxic diarylsulphonylurea compounds. The negative coefficient of the descriptor Wiener Path suggests that increased branching in the side chain and resultant decrease in its flexibility is conducive for cytotoxic activity.
  C. Karthikeyan , Dengale Santosh , N.S. Hari Narayana Moorthy and Piyush Trivedi
  Shailendra Mandge , Hemendra P. Singh , S. Dutta Gupta and N.S. Hari Narayana Moorthy
  Chalcones are the important constituent of many natural sources and have variety of biological activities. A series of chalcone derivatives were synthesized and their structure also confirmed. The compounds were synthesized by Claisen-Shimidt base catalyzed condensation of appropriate aromatic ketones or substituted aromatic ketones with benzaldehydes or substituted benzaldehydes. The structures of the synthesized compounds were confirmed by IR, mass spectroscopy and elemental analysis.
  Surya Prakash B.N. Gupta and N.S. Hari Narayana Moorthy
  Indomethacin, which causes gasterointestional side effect and that, may be minimized by design and development of mutual prodrugs. It involves combining two different pharmacophores with similar pharmacological activities to give synergistic action. The drug (indomethacin) was esterified with paracetamol to prepare mutual prodrug. The structure of the prodrug was confirmed on the basis of IR, 1[H] NMR, mass spectroscopy and elemental analysis. Various physicochemical properties such as solubility in water and organic solvents like chloroform, ether, acetone, methanol and ethanol and partition coefficient in octanol-water, octanol-hydrochloric acid buffer (pH 1.2) and in octanol phosphate buffer (pH 7.4) were determined. In acid pH, the mutual prodrug cannot undergo dissociation and only can undergo in intestinal pH. The mutual prodrug may have devoid of gastric irritation in GIT due to its unionized form in stomach and ionized form in intestine and may have synergic action due to two drugs are combined together. The results indicate that the prodrug dissociate in the intestinal pH because of less partition coefficient in octanol phosphate buffer.
  Richa Mishra , Brijeshkunvar Mishra and N.S. Hari Narayana Moorthy
  4-phenyl-5-carboxyethyl-6-methyl-1,2,3,4-tetrahydropyrimidin-2-ones have been synthesized using the principle of Biginelli condensation from easily available starting materials. The carboethoxy group at the C5 position of the pyrimidine ring is converted to corresponding hydrazide which in turn is condensed with cyclizing agents such as aromatic aldehyde, CS2 to give fused heterocycles. The fused heterocycles are then subjected to substitution to give N3-aryl/alkylpyrimido-heterocycles in excellent yields. The compounds were tested for antimicrobial action relative to Norfloxacin against Gram positive and Gram negative bacteria using serial dilution technique.
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