Discovery and optimization of novel 4-phenoxy-6,7-disubstituted quinolines possessing semicarbazones as c-Met kinase inhibitors

Qi, Baohui; Mi, Bin; Zhai, Xin; Xu, Ziyi; Zhang, Xiaolong; Tian, Zeru; Gong, Ping

doi:10.1016/j.bmc.2013.06.026

Cited by 48 publications

(13 citation statements)

References 29 publications

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“…Thiosemicarbazide analogues possess a wide range of biological activities including anticonvulsant (Tripathi et al, 2012), antimicrobial (Zhong et al, 2011), antiviral (Garcial et al, 2003), antitrypanosomal (Moreira et al, 2014), and mushroom tyrosinase inhibitors (Yi et al, 2011). On the other hand, Semicarbazide analogues exhibit anticonvulsant (Rajak et al, 2013), antitubercular (Sriram et al, 2004), antitrypanosomal (Cerecetto et al, 2000), anti inflammatory (Vieira et al, 2012), anti amnesic, cognition enhancing and anticholinesterase (Sinha and Shrivastava, 2013) and anticancer activity (Qi et al, 2013 …”

Section: Introductionmentioning

confidence: 98%

Design, synthesis of novel N prenylated indole-3-carbazones and evaluation of in vitro cytotoxicity and 5-LOX inhibition activities

Choppara

Prasad

Rao

et al. 2019

Arabian Journal of Chemistry

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A series of novel N-1 and C-3 substituted indole derivatives (5a-f) were designed, synthesized and evaluated for their cytotoxic properties, viz Brine Shrimp Lethality Bioassay (BSLB) besides 5-Lipoxygenase (5-LOX) inhibitory activities through in vitro assays. Structure Activity Relation (SAR) studies showed that compound 5d with an LC 50 of 6.49 lM and 5c with an IC 50 of 33.69 lM were found to be interesting for cytotoxicity and 5-LOX inhibitory activity respectively. ª 2015 Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Section: Introductionmentioning

confidence: 98%

Design, synthesis of novel N prenylated indole-3-carbazones and evaluation of in vitro cytotoxicity and 5-LOX inhibition activities

Choppara

Prasad

Rao

et al. 2019

Arabian Journal of Chemistry

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“…In the present work, we planned to produce intermediate semicarbazide 6 [25] in one pot, and then in the same pot, incorporate it to the several different aliphatic, alicyclic, and aromatic ketones and aldehydes 4 to produce semicarbazone 1 (route 2) (Scheme 1). Key intermediate semicarbazides 6 [26,27] prepared via route 1 involved the reaction of amines with phenyl chloroformate 2 to create the corresponding carbamates 3, consequently under hydrazinolysis by hydrazine hydrate to 6 [26][27][28] (Scheme 1). The newly synthesized 1 were screened for their antibacterial activity against five bacteria strains, including Bacillus cereus (B. cereus) ATCC 11778, Enterococcus fecalis (E. fecalis) ATCC 29212, Escherichia coli (E. coli) ATCC 25922, Pseudomonas aeruginosa (P. aeruginosa) ATCC 27853, and Staphylococcus aureus (S. aureus) ATCC 25923.…”

Section: Introductionmentioning

confidence: 99%

Practical one-pot synthesis of semicarbazone derivatives via semicarbazide, and evaluation of their antibacterial activity

et al. 2015

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New series of 2-(aryl or alkyl)-N-phenylhydrazine-1-carboxamides 1a-j were synthesized through one-pot reactions of aldehyde or ketones, hydrazine hydrate, and phenylisocyanate in MeOH. The structure of products was confirmed by Fourier transform infrared (FT-IR), proton nuclear magnetic resonance ( 1 H NMR), and 13 C NMR spectra. Minimum inhibitory concentration (MIC) of antibacterial activity of 1a-j was screened against five bacterial strains. Compound 1f showed antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus.

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“…And the structureactivity relationships of the c-Met type II inhibitors to c-Met were systematically investigated based on the computationally determined binding modes. The large number of c-Met inhibitors with reported activities [9,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] as well as the six c-Met crystal structures (pdb code: 2WGJ, 2WKM, 3ZXZ, 3ZZE, 3LQ8 and 3U6I) [11,12,14,32] in complex with some of these inhibitors gave rise to the possibility to test our methods.…”

Section: Introductionmentioning

confidence: 99%

Development of efficient docking strategies and structure-activity relationship study of the c-Met type II inhibitors

Kaas

et al. 2017

Journal of Molecular Graphics and Modelling

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Graphical AbstractTOC c-Met is a tyrosine kinase and an important therapeutic target for anticancer drugs. In present study, we systematically investigated the influence of a range of parameters on the correlation between experimental and calculated binding energies of type II c-Met inhibitors. Results from this study will form the basis for establishing an efficient computational docking approach for c-Met type II inhibitors design. Highlights• Testing a set of influences to the ranking ability of the docking program in MOE.• Structure-activity relationship study of c-Met type II inhibitors.• Establishing an efficient computational docking approach for c-Met type II inhibitors design.ABSTRACT： c-Met is a transmembrane receptor tyrosine kinase and an important therapeutic target for anticancer drugs. In the present study, we systematically investigated the influence of a range of parameters on the correlation between experimental and calculated binding free energies of type II c-Met inhibitors. We especially focused on evaluating the impact of different force fields, binding energy calculation methods, docking protocols, conformation sampling strategies, and conformations of the binding site captured in several crystallographic structures. Our results suggest that the force fields, the protein flexibility, and the selected conformation of the binding site substantially influence the correlation coefficient, while the sampling strategies and ensemble docking only mildly affect the prediction accuracy. Structure-activity relationship study suggests that the structural determinants to the high binding affinity of the type II inhibitors originate from its overall linear shape, hydrophobicity, and two conserved hydrogen bonds. Results from this study will form the basis for establishing an efficient computational docking approach for c-Met type II inhibitors design.

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Discovery and optimization of novel 4-phenoxy-6,7-disubstituted quinolines possessing semicarbazones as c-Met kinase inhibitors

Cited by 48 publications

References 29 publications

Design, synthesis of novel N prenylated indole-3-carbazones and evaluation of in vitro cytotoxicity and 5-LOX inhibition activities

Design, synthesis of novel N prenylated indole-3-carbazones and evaluation of in vitro cytotoxicity and 5-LOX inhibition activities

Practical one-pot synthesis of semicarbazone derivatives via semicarbazide, and evaluation of their antibacterial activity

Development of efficient docking strategies and structure-activity relationship study of the c-Met type II inhibitors

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