575451-29-5

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• 59-48-3 2-oxoindole 
• 620-23-5 m-tolyl aldehyde 

Relevant academic research and scientific papers

Solvent-free synthesis of novel spirocyclic oxindole derivatives via a Michael-aldol cascade by grinding

A simple and novel synthesis of spirocyclic oxindole derivatives by the reaction of (E)-3-arylideneindole-2-ones and 1,4-dithiane-2,5-diol via a Michael-aldol cascade under solvent-free reaction conditions is reported. This method provides a new practical and facile approach to 4′-hydroxy-2′-aryl-4′,5′-dihydro-2′H-spiro[oxindole-3,3′-thiophen]-2-ones in moderate to good yields. The structures of all the products were characterised by NMR, infrared spectroscopy and HRMS.

Natural α-methylenelactam analogues: Design, synthesis and evaluation of α-alkenyl-γ and δ-lactams as potential antifungal agents against Colletotrichum orbiculare

In our continued efforts to improve the potential utility of the α-methylene-γ-lactone scaffold, 62 new and 59 known natural α-methylenelactam analogues including α-methylene-γ-lactams, α-arylidene-γ and δ-lactams, and 3-arylideneindolin-2-ones were synthesized as the bioisosteric analogues of the α-methylenelactone scaffold. The results of antifungal and cytotoxic activity indicated that among these derivatives compound (E)-1-(2, 6-dichlorobenzyl)-3-(2-fluorobenzylidene) pyrrolidin-2-one (Py51) possessed good selectivity with the highest antifungal activity against Colletotrichum orbiculare with IC50?=?10.4?μM but less cytotoxic activity with IC50?=?141.2?μM (against HepG2 cell line) and 161.2?μM (against human hepatic L02?cell line). Ultrastructural change studies performed by transmission electron microscope showed that Py51 could cause important cell morphological changes in C.?orbiculare, such as plasma membrane detached from cell wall, cell wall thickening, mitochondria disruption, a dramatic increase in vacuolation, and eventually a complete loss in the integrity of organelles. Significantly, mitochondria appeared one of the primary targets, as confirmed by their remarkably aberrant morphological changes. Analysis of structure–activity relationships revealed that incorporation of the aryl group into the α-exo-methylene and the N-benzyl substitution increased the activity. Meanwhile, the α-arylidene-γ-lactams have superiority in selectivity over the 3-arylideneindolin-2-ones. Based on the results, the N-benzyl substituted α-(2-fluorophenyl)-γ-lactam was identified as the most promising natural-based scaffold for further discovering and developing improved crop-protection agents.

Functionalized 3-benzylidene-indolin-2-ones: Inducers of NAD(P)H-quinone oxidoreductase 1 (NQO1) with antiproliferative activity

Functionalized benzylidene-indolin-2-ones are widely associated with antiproliferative activity. The scaffold is not normally associated with chemoprevention in spite of the presence of a nitrogen-linked Michael acceptor moiety that may predispose members to induction of NQO1, a widely used biomarker of chemopreventive potential. To investigate this possibility, we have synthesized and evaluated a series of functionalized 3-benzylidene-indolin-2-ones for induction of NQO1 in murine Hepa1c1c7 cells as well as antiproliferative activity against two human cancer cell lines (MCF-7, HCT116). The benzylideneindolinones were found to be good inducers of NQO1 activity, with 85% of test compounds able to increase basal NQO1 activity by more than twofold at concentrations of ≤10 μM. By contrast, fewer compounds (11%) tested at the same concentration were able to reduce cell viability by more than 50%. Structure activity relationships showed that the nitrogen linked Michael acceptor moiety was an essential requirement for both activities. This common feature notwithstanding, substitution of the 3-benzylidene-indolin-2-one core structure affected NQO1 induction and antiproliferative activities in dissimilar ways, underscoring different structural requirements for these two activities. Nonetheless, promising compounds (10, 42, 45-48) were identified that combine selective induction of NQO1 with potent antiproliferative activity. A potential advantage of such agents would be the ability to provide added protection to normal cells by the up-regulation of NQO1 and other phase II enzymes while simultaneously targeting neoplastic cells.