Pharmaceutical Sciences and Natural Products - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/56

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Author: search.filters.author.Dwivedi, Ashish RanjanHas files: Yes

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    Synthesis, Biological Evaluation and Molecular Modeling Studies of Propargyl‐Containing 2,4,6‐Trisubstituted Pyrimidine Derivatives as Potential Anti‐Parkinson Agents
    (Wiley, 2018) Kumar, Bhupinder; Kumar, Mohit; Dwivedi, Ashish Ranjan; Kumar, Vinod
    Monoamine oxidase B (MAO‐B) inhibitors are potential drug candidates for the treatment of various neurological disorders including Parkinson's disease. A total of 20 new propargyl‐containing 2,4,6‐trisubstituted pyrimidine derivatives were synthesized and screened for MAO inhibition using Amplex Red assays. All the synthesized compounds were found to be reversible and selective inhibitors of the MAO‐B isoform at sub‐micromolar concentrations. MVB3 was the most potent MAO‐B inhibitor with an IC50 value of 0.38±0.02 μμ, whereas MVB6 (IC50=0.51±0.04 μμ) and MVB16 (IC50=0.48±0.06 μμ) were the most selective for MAO‐B with a selectivity index of more than 100‐fold. In cytotoxic studies, these compounds were found to be nontoxic to human neuroblastoma SH‐SY5Y cells at concentrations of 25 μm. MVB6 was found to decrease the intracellular level of reactive oxygen species to 68 % at 10 μm concentration, whereas other compounds did not produce significant changes in reactive oxygen species levels. In molecular modeling studies, MVB3 displayed strong binding affinity for the MAO‐B isoform with a dock score of −10.45, in agreement with the observed activity. All the compounds fitted well in the hydrophobic cavity of MAO‐B. Thus, propargyl‐substituted pyrimidine derivatives can be promising leads in the development of potent, selective and reversible MAO‐B inhibitors for the treatment of Parkinson's disease.
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    Regioselective alkylation of 1,2,4-triazole using ionic liquids under microwave conditions
    (Walter de Gruyter GmbH, 2016) Kaur,Ramandeep; Kumar, Bhupinder; Dwivedi, Ashish Ranjan; Kumar, Vinod
    1-Substituted 1,2,4-triazole derivatives present in a large number of compounds and display a variety of bioactivities such as antibiotic, anti-inflammatory, anti-diabetic, antipsychotic, and anticancer. A regioselective protocol has been developed for the alkylation of 1,2,4- triazole using mild conditions. The 1-alkyl-1,2,4-triazole derivatives were synthesized under microwave conditions using potassium carbonate as a base and ionic liquid (hexylpyridinium bromide) as a solvent. The products were obtained in excellent yield, and the base-ionic liquid combination was recycled for a number of times. ? 2016 by De Gruyter 2016.
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    Recent developments on 1,2,4-triazole nucleus in anticancer compounds: A review
    (Bentham Science Publishers B.V., 2016) Kaur, Ramandeep; Dwivedi, Ashish Ranjan; Kumar, Bhupinder; Kumar, Vinod
    1,2,4 triazole is an important nucleus present in a large number of compounds. More than thirty-five compounds containing this nucleus are introduced into the market. 1,2,4-triazole nucleus is stable to metabolism and acts as an important pharmacophore by interacting at the active site of a receptor as hydrogen bond acceptor and as a donor. Due to its polar nature, the triazole nucleus can increase the solubility of the ligand and it can significantly improve the pharmacological profile of the drug. A large number of 1,2,4-triazole derivatives are reported to possess a wide range of bioactivities including anti-cancer activity. This review article describes the role of 1,2,4-triazole nucleus in different types of anti-cancer agents such as nucleoside based anti-cancer agents, kinase inhibitors, tubulin modulators, aromatase and steroid sulfatase inhibitors, methionine aminopeptidase inhibitors, tankyrase inhibitors and metal complex based anti-cancer agents. It is expected that the current review article will provide insight into various ligand-receptor interactions and help in the rational design and development of novel 1,2,4-triazole based anti-cancer drugs with improved selectivity for cancer cells. ? 2016 Bentham Science Publishers.