Synthesis and biological evaluation of spiro[cyclopropane-1,3′-indolin]-2′-ones as potential anticancer agents

Reddy, Chada Narsimha; Nayak, Vijayashree; Mani, Ganesh Kumar; Kapure, Jeevak Sopanrao; Adiyala, Praveen Reddy; Maurya, Ram Awatar; Kamal, Ähmed

doi:10.1016/j.bmcl.2015.08.056

Cited by 65 publications

(15 citation statements)

References 32 publications

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“…While synthetic efforts have focused on constructing C3‐spirofused five‐ and six‐membered rings, only recently has the spirooxindole cyclopropane emerged as a scaffold for guided drug design . In contrast to the rich history of 2‐oxindoles, reports of spirooxindole cyclopropanes as architectural templates for therapeutic exploitation are limited . Based on parallels drawn to known spirooxindole leads, as well as our initial compound screening, we targeted a series of derivatives around a central cyclopropane with 1) the 2‐oxindole motif, 2) an aromatic substituent, and 3) geminal donor/acceptor functionality as three main points of variability (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Combined Scaffold Evaluation and Systems‐Level Transcriptome‐Based Analysis for Accelerated Lead Optimization Reveals Ribosomal Targeting Spirooxindole Cyclopropanes

et al. 2019

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With evolutionary drug resistance impacting efforts to treat disease, the need for small molecules that exhibit novel molecular mechanisms of action is paramount. In this study, we combined scaffold‐directed synthesis with a hybrid experimental and transcriptome analysis to identify bis‐spirooxindole cyclopropanes that inhibit cancer cell proliferation through disruption of ribosomal function. These findings demonstrate the value of an integrated, biologically inspired synthesis and assay strategy for the accelerated identification of first‐in‐class cancer therapeutic candidates.

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Section: Resultsmentioning

confidence: 99%

Combined Scaffold Evaluation and Systems‐Level Transcriptome‐Based Analysis for Accelerated Lead Optimization Reveals Ribosomal Targeting Spirooxindole Cyclopropanes

et al. 2019

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“…[38][39] Such spiro cyclopropyloxindoles constitute an important group of heterocycles with potential application in medical research, including the use as potent HIV inhibitor [40][41][42] and antitumor agent. [43][44][45][46] Despite their high activity and selectivity, the unsatisfactory catalyst recovery and recycling of the costly manufactured chiral dirhodium catalysts is the primary limiting factor for their application in chemical industry. Thus, several approaches have been proposed to handle the catalyst recovery as reviewed by Gois and co-workers.…”

Section: Introductionmentioning

confidence: 99%

Dirhodium Coordination Polymers for Asymmetric Cyclopropanation of Diazooxindoles with Olefins: Synthesis and Spectroscopic Analysis

Rösler

Herr

et al. 2020

ChemPlusChem

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A facile approach is reported for the preparation of dirhodium coordination polymers [Rh2(L1)2]n (Rh2‐L1) and [Rh2(L2)2]n (Rh2‐L2; L1=N,N’‐(pyromellitoyl)‐bis‐L‐phenylalanine diacid anion, L2=bis‐N,N’‐(L‐phenylalanyl) naphthalene‐1,4,5,8‐tetracarboxylate diimide) from chiral dicarboxylic acids by ligand exchange. Multiple techniques including FTIR, XPS, and 1H→13C CP MAS NMR spectroscopy reveal the formation of the coordination polymers. 19F MAS NMR was utilized to investigate the remaining TFA groups in the obtained coordination polymers, and demonstrated near‐quantitative ligand exchange. DR‐UV‐vis and XPS confirm the oxidation state of the Rh center and that the Rh‐single bond in the dirhodium node is maintained in the synthesis of Rh2‐L1 and Rh2‐L2. Both coordination polymers exhibit excellent catalytic performance in the asymmetric cyclopropanation reaction between styrene and diazooxindole. The catalysts can be easily recycled and reused without significant reduction in their catalytic efficiency.

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“…Inflammation, encompassing the innate and adaptive immune systems, is a typical reaction to infection. Even though it seems non‐harm, it has the capability to induce or develop many opposing effects in autoimmune diseases, hypersensitivity, and undesirable reactions of transplanted organs .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Molecular Drug Efficacy of Indoline‐based Dihydroxy‐thiocarbamides: Inflammation Regulatory Property Unveiled over COX‐2 Inhibition, Molecular Docking, and Cytotoxicity Prospects

M¹,

Dhayabaran²

2018

Journal of Heterocyclic Chem

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in Wiley Online Library (wileyonlinelibrary.com).In this study, substituted indoline-based dihydroxy-carbamides (5a-i) were synthesized and evaluated as the cyclooxygenase-2 (COX-2) inhibitors to testify their inflammatory regulations through COX-2 inhibition. Enzyme-linked immunosorbent assay-based competitive (COX-2) inhibition (in vitro) followed by a molecular docking study (in silico) was executed to ensure the mode of interaction between 5a-i and COX-2. Apart from COX-2 inhibition studies, free-radical scavenging ability (H 2 O 2 estimation method) and the human red blood cell membrane protection (in vitro anti-inflammatory) capability of the compounds 5a-i assessment were also evaluated. Excellent antimicrobial and anticancer activity exhibited by thiocarbamide substituted compounds (5a-d) than carbamide (5e-i). In molecular docking studies, the obtained binding affinity values of 5a-i indicated the therapeutic selectivity on COX-2 (PDB ID: 1CX2) over COX-1 (PDB ID: 1EQG). Established inhibitory constant (ki) values were found as low as in nanomolar/picomolar against COX-2. Reliable COX-2 inhibition of 78-92% and IC 50 0.002-1.28 μM were obtained. Human red blood cell membrane was found to be effectively stabilized/protected by 5a-i up to 98%. Excellent antioxidant property (average radical scavenging 92%) and structure-activity relationship predictions confirmed the druggability potentials of 5a-i as effective, future anti-inflammatory drugs. The cytotoxicity of the compounds was also unveiled by MTT assay using MCF-7 (human breast cancer), SW620 (human colon cancer), G361 (human skin cancer), human breast normal cell lines (MCF-10), and cell lines.

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Synthesis and biological evaluation of spiro[cyclopropane-1,3′-indolin]-2′-ones as potential anticancer agents

Cited by 65 publications

References 32 publications

Combined Scaffold Evaluation and Systems‐Level Transcriptome‐Based Analysis for Accelerated Lead Optimization Reveals Ribosomal Targeting Spirooxindole Cyclopropanes

Combined Scaffold Evaluation and Systems‐Level Transcriptome‐Based Analysis for Accelerated Lead Optimization Reveals Ribosomal Targeting Spirooxindole Cyclopropanes

Dirhodium Coordination Polymers for Asymmetric Cyclopropanation of Diazooxindoles with Olefins: Synthesis and Spectroscopic Analysis

Synthesis and Molecular Drug Efficacy of Indoline‐based Dihydroxy‐thiocarbamides: Inflammation Regulatory Property Unveiled over COX‐2 Inhibition, Molecular Docking, and Cytotoxicity Prospects

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