Department Of Pharmaceutical Sciences and Natural Products

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Author: search.filters.author.Kalra, SHas 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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    Relay tricyclic Pd (ii)/Ag (i) catalysis: design of a four-component reaction driven by nitrene-transfer on isocyanide yields inhibitors of EGFR.
    (Royal Society of Chemistry, 2018) Sawant, D.M.; Sharma, S; Pathare, R.S; Joshi, G; Kalra, S; Sukanya, S; Maurya, A.K.; Metre, R.K; Agnihotri, V.K.; Khan, S.; Kumar, Raj; Pardasania, R. T.
    Synthesis of pyrazolo[1,5-c]quinazolines from four easily available precursors is presented through a one-pot tricyclic Pd(II)/Ag(I) relay catalysis. The bimetallic relay cascade forges five new chemical bonds by concatenating six discrete chemical steps. The relay catalysis enables four-component assembly of pyrazolo[1,5-c]quinazolines that selectively inhibit EGFR, exhibit apoptosis through the ROS-induced mitochondrial-mediated pathway, and arrest the cell cycle at the G1 phase.
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    Novel 2-(substituted phenyl Imino)-5-benzylidene-4-thiazolidinones as possible non-ulcerogenic tri-action drug candidates: synthesis, characterization, biological evaluation And docking studies.
    (Springer, 2019) Chawla, P.; Kalra, S; Kumar, R; Ranjit, S; Saraf, S.
    The present research was aimed at the synthesis and screening of 35 novel 2-(substituted phenyl imino)-5-benzylidene-4-thiazolidinones having different substitutions at imino phenyl and arylidene groups. The title compounds were synthesized by Knoevenagel condensation at the 5th position of the 4-thiazolidinone ring, in the presence of sodium acetate. The structures were assigned on the basis of spectral data. The compounds were screened for in vivo anti-inflammatory, antinociceptive and in vitro free-radical scavenging activities. The compounds exhibited significant activities when compared with standard drugs. The distinctive property of the derivatives was that none of them had an acidic group, like conventional NSAIDs, but exhibited significant in vivo activity in acute inflammation models. Further, the active compounds of each series were docked against cyclooxygeanase (COX)-2 enzyme using Glide module of Maestro 11.1 program. It was evident from the docking results that 3-chlorophenylimino and 2-chloro moiety on 5-benzylidene nucleus of the 4-thiazolidinone derivative (30) could easily fit into the COX-2-binding pocket, considered as critical interaction for COX-2 inhibition. Interestingly, some of the compounds exhibited the potential of becoming dual action or even triple action drug candidates, which could target degenerative disorders associated with excessive free-radical generation.