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.Kumar, R

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    Exploration of Pd-catalysed four-component tandem reaction for one-pot assembly of pyrazolo[1,5-c]quinazolines as potential EGFR inhibitors
    (Academic Press Inc., 2019) Ansari, A.J; Joshi, G; Yadav, U.P; Maurya, A.K; Agnihotri, V.K; Kalra, S; Kumar, R; Singh, S; Sawant, D.M.
    A series of pyrazolo[1,5-c]quinazolines as EGFR inhibitors was designed and synthesized by highly efficient and novel multicomponent route involving Pd-catalyzed tandem one-pot four-component reaction. The reaction proceeds with good functional group tolerance under a simple condition with excellent regioselectivity and high efficiency. Target compounds were screened against cancer cell lines MDA-MB-231, A549 and H1299. Of these, 9b and 10b exhibited superior anticancer activity (IC50 < 2.5 ?M) to erlotinib and gefitinib. Synthetics were able to inhibit EGFR mediated kinase activity, induced ROS in cancer cells promoting mitochondrial mediated apoptosis via halting cell cycle progression at G1 phase.
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    Cyclocondensation reactions of an electron deactivated 2-aminophenyl tethered imidazole with mono/1, 2-biselectrophiles: synthesis and DFT studies on the rationalisation of imidazo [1, 2-a] quinoxaline versus benzo [f] imidazo [1, 5-a][1, 3, 5] triazepine selectivity switches.
    (Royal Society of Chemistry, 2018) Joshi, G.; Chauhan, M; Kumar, R; Thakur, A; Sharma, S; Singh, R.; Wani, A.A.; Sharon, A.; Bharatam, P.V; Kumar, R.
    Microwave-promoted ring-closure reactions of 5-amino-1-(2-aminophenyl)-1H-imidazole-4-carbonitrile (7) with various mono/1,2-biselectrophiles are presented. The reaction of 7 with aldehydes, ketones and isocyanates produced the corresponding Pictet–Spengler (PS) products i.e. the imidazo[1,2-a]quinoxaline ring system via 6-endo-trig cyclisation. On the other hand, the reaction of 7 with CH(OEt)3, and CDI resulted in the formation of benzo[f]imidazo[1,5-a][1,3,5]triazepine scaffolds via a 7-exo-trig cyclisation process. The mechanistic aspects of these ring cyclisation processes have been analysed and studied to rationalise 6- versus 7-membered ring formation using density functional theory (DFT). DFT calculations revealed the involvement of N-Heterocyclic Carbene (NHC) in the PS reaction mechanism.
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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.