Pharmaceutical Sciences and Natural Products - Research Publications

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Author: search.filters.author.Kumar, PradeepHas files: Yes

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    Knoevenagel/tandem knoevenagel and michael adducts of cyclohexane-1,3-dione and aryl aldehydes: Synthesis, DFT studies, xanthine oxidase inhibitory potential, and molecular modeling
    (American Chemical Society, 2019) Arora, S; Joshi, G; Kalra, S; Wani, A.A; Bharatam, P.V; Kumar, Pradeep; Kumar, Raj
    Xanthine oxidase (XO) plays a crucial role in the formation of uric acid by oxidative hydroxylation of purines. Herein, we report the design and synthesis of Knoevenagel/tandem Knoevenagel and Michael adducts of cyclohexane-1,3-dione and aryl aldehydes as nonpurine XO inhibitors derived from naturally occurring scaffolds. Density functional theory calculations highlighted the reaction pathways and reasoned the formation of tandem Knoevenagel and Michael adducts. The synthetics were assessed for their XO inhibitory potential, and among them, four compounds (1b, 1g, 2b, and 3a) were found to possess best IC 50 values in the range of 3.66-4.98 μM. Interestingly, Knoevenagel adducts exhibited a competitive-type inhibition, whereas tandem Knoevenagel and Michael adducts produced a noncompetitive mode of inhibition. The compounds were capable of reducing the H 2 O 2 levels induced by XO, both in normal and cancer cells with no significant cytotoxicity. Molecular modeling studies highlighted the role of interactions of compounds with residual amino acids of the XO active site and also corroborated with the observed structure-activity relationship. © 2019 American Chemical Society.
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    Computer-aided design of negative allosteric modulators of metabotropic glutamate receptor 5 (mGluR5): Comparative molecular field analysis of aryl ether derivatives
    (Elsevier Ltd, 2016) Selvam, Chelliah; Thilagavathi, Ramasamy; Narasimhan, Balasubramanian; Kumar, Pradeep; Jordan, Brian C.; Ranganna, Kasturi; Selvam, C.; Thilagavathi, R.; Narasimhan, B.; Kumar, P.; Jordan, B.C.; Ranganna, K.
    The metabotropic glutamate receptors (mGlu receptors) have emerged as attractive targets for number of neurological and psychiatric disorders. Recently, mGluR5 negative allosteric modulators (NAMs) have gained considerable attention in pharmacological research. Comparative molecular field analysis (CoMFA) was performed on 73 analogs of aryl ether which were reported as mGluR5 NAMs. The study produced a statistically significant model with high correlation coefficient and good predictive abilities. ? 2016