Synthesis and biological evaluation of [4-(2-phenylethenesulfonylmethyl)phenyl]-quinazolin-4-yl-amines as orally active anti-cancer agents

Sharma, Vedula M.; Seshu, K.V. Adi; Sekhar, V. Chandra; Madan, Sachin; Vishnu, B.; Babu, P. Aravind; Krishna, C. Vamsee; Sreenu, J.; Krishna, V. Ravi; Venkateswarlu, A.; Rajagopal, Sriram; Ajaykumar, R.; Kumar, Terrence

doi:10.1016/j.bmcl.2003.10.020

Cited by 20 publications

(5 citation statements)

References 11 publications

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“…It has been reported that the members of the spiroquinazolinone family are cytotoxic to several types of cancer cells (Shenoy et al, 2007;Sharma et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Spiroquinazolinone-induced cytotoxicity and apoptosis in K562 human leukemia cells: alteration in expression levels of Bcl-2 and Bax

et al. 2015

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-Spiroquinazolinone compounds have been considered as a new series of potent apoptosis-inducing agents. In this study, anti-proliferative and apoptotic effects of the derivatives from the spiroquinazolinone family were investigated in the human chronic myeloid leukemia K562 cells. The K562 cells were treated with various concentrations of the spiroquinazolinone (10-300 μM) for 3 days and cell viability was determined by MTT growth inhibition assay. 4t-QTC was more active among these compounds with IC50 of 50 ± 3.6 μM and was selected for further studies. Apoptosis, as the mechanism of cell death was investigated morphologically by acridine orange/ethidium bromide (AO/EtBr) double staining, cell surface expression assay of phosphatidyl serine by Annexin V/PI technique, as well as the formation of DNA ladder. The K562 cells underwent apoptosis upon a single dose (at IC50 value) of the 4t-QTC compound, and over-expressed caspase-3 expression by more than 1.7-fold, following a 72 hr treatment. Furthermore, RT-PCR and Western blot analysis revealed that treatment of the K562 cells with 4t-QTC down-regulates and up-regulates the expression of Bcl-2 (anti-apoptotic) and Bax (pro-apoptotic), respectively. Based on the present data, it seems that these compounds from the spiroquinazolinone family are good candidates for further evaluation as an effective chemotherapeutic family acting through induction of apoptosis in chronic myeloid leukemia.

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“…It has been reported that the members of the spiroquinazolinone family are cytotoxic to several types of cancer cells (Shenoy et al, 2007;Sharma et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Spiroquinazolinone-induced cytotoxicity and apoptosis in K562 human leukemia cells: alteration in expression levels of Bcl-2 and Bax

et al. 2015

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“…Alkyl ( E )-vinyl sulfides and their oxidized derivatives are used in a wide range of synthetic transformations, including cross-coupling, Heck reactions, sigmatropic rearrangements, Diels−Alder reactions, and Pauson−Khand reactions and as ligands for a number of transformations, including C−H activation and allylic alkylation . Moreover, benzyl ( E )-vinyl sulfones, which are readily accessible from alkyl ( E )-vinyl sulfides, are inhibitors of polo-like kinase 1 (PLK1), MAP kinase, and cysteine protease . Indeed, the PLK1 inhibitor ON01910 is currently in clinical trials for anticancer activity 10c…”

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confidence: 99%

Catalytic Alkyne Hydrothiolation with Alkanethiols using Wilkinson's Catalyst

et al. 2007

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We recently discovered that Wilkinson's catalyst (ClRh(PPh3)3) is an excellent catalyst for alkyne hydrothiolation with alkanethiols to provide linear alkyl (E)-vinyl sulfides, which are valuable synthetic intermediates and precursors to bioactive molecules. Deuterium-labeling studies indicate that the reaction proceeds by thiol oxidative addition, alkyne migratory insertion, and subsequent reductive elimination.

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“…General procedure for the synthesis of (Sharma et al, 2004). To a solution of the crude product 2-((3-methylbenzyl) thio) acetic acid in dichloromethane (20 mL) was added dropwise in oxalyl chloride (0.48 g, 3.80 mmol, 1.2 eqv) at 0 • C. The reaction was stirred for 0.5 h at 0 • C, then was stirred for 1 h at room temperature, after which excessive oxalyl chloride and dichloromethane was removed to get the crude compound 3.…”

Section: Synthetic Proceduresmentioning

confidence: 99%

Design, Synthesis, and Action Mechanism of 1,3-Benzodioxole Derivatives as Potent Auxin Receptor Agonists and Root Growth Promoters

Yang

Xu²,

Li³

et al. 2022

Front. Plant Sci.

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Deeper and longer roots allow crops to survive and flourish, but our understanding of the plant growth regulators promoting root system establishment is limited. Here, we report that, a novel auxin receptor agonist, named K-10, had a remarkable promotive effect on root growth in both Arabidopsis thaliana and Oryza sativa through the enhancement of root-related signaling responses. Using computer-aided drug discovery approaches, we developed potent lead compound by screening artificial chemicals on the basis of the auxin receptor TIR1 (Transport Inhibitor Response 1), and a series of N-(benzo[d] [1,3] dioxol-5-yl)-2-(one-benzylthio) acetamides, K-1 to K-22, were designed and synthesized. The results of bioassay showed that K-10 exhibited an excellent root growth-promoting activity far exceeding that of NAA (1-naphthylacetic acid). A further morphological investigation of the auxin related mutants (yucQ, tir1) revealed that K-10 had auxin-like physiological functions and was recognized by TIR1, and K-10 significantly enhanced auxin response reporter’s (DR5:GUS) transcriptional activity. Consistently, transcriptome analysis showed that K-10 induced a common transcriptional response with auxin and down-regulated the expression of root growth-inhibiting genes. Further molecular docking analysis revealed that K-10 had a stronger binding ability with TIR1 than NAA. These results indicated that this class of derivatives could be a promising scaffold for the discovery and development of novel auxin receptor agonists, and the employment of K-10 may be effective for enhancing root growth and crop production.

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Synthesis and biological evaluation of [4-(2-phenylethenesulfonylmethyl)phenyl]-quinazolin-4-yl-amines as orally active anti-cancer agents

Cited by 20 publications

References 11 publications

Spiroquinazolinone-induced cytotoxicity and apoptosis in K562 human leukemia cells: alteration in expression levels of Bcl-2 and Bax

Spiroquinazolinone-induced cytotoxicity and apoptosis in K562 human leukemia cells: alteration in expression levels of Bcl-2 and Bax

Catalytic Alkyne Hydrothiolation with Alkanethiols using Wilkinson's Catalyst

Design, Synthesis, and Action Mechanism of 1,3-Benzodioxole Derivatives as Potent Auxin Receptor Agonists and Root Growth Promoters

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