Design, synthesis and molecular docking studies of some novel spiro[indoline-3, 4′-piperidine]-2-ones as potential c-Met inhibitors

Ye, Lianbao; Tian, Yuanxin; Li, Zhonghuang; Jin, Hong; Zhu, Zuo-Nong; Wan, Shanhe; Zhang, Junyan; Yu, P.Y.; Zhang, Jiajie; Wu, Shuai

doi:10.1016/j.ejmech.2012.02.016

Cited by 33 publications

(14 citation statements)

References 16 publications

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“…Molecular docking was performed according to related reference [25]. The docking experiment was carried out with CDocker program which was connected with Accelrys Discovery Studio 2.5.5.…”

Section: Methodsmentioning

confidence: 99%

Germacrone derivatives: synthesis, biological activity, molecular docking studies and molecular dynamics simulations

Feng

Han

et al. 2017

Oncotarget

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Germacrone is one of the major bioactive components in the Curcuma zedoaria oil product, which is extracted from Curcuma zedoaria Roscoe, known as zedoary. The present study designed some novel germacrone derivatives based on combination principles, synthesized these compounds, and investigated their inhibitions on Bel-7402, HepG2, A549 and HeLa cells. Meanwhile, the study evaluated inhibitions of these derivatives on c-Met kinase, which has been detected in a number of cancers. The results suggested that the majority of the compounds showed stronger inhibitory effect on cancers and c-Met kinase than germacrone. Furthermore, our docking experiments analyzed the results and explained the molecular mechanism. Molecular dynamics simulations were then applied to perform further evaluation of the binding stabilities between compounds and their receptors.

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“…Molecular docking was performed according to related reference [25]. The docking experiment was carried out with CDocker program which was connected with Accelrys Discovery Studio 2.5.5.…”

Section: Methodsmentioning

confidence: 99%

Germacrone derivatives: synthesis, biological activity, molecular docking studies and molecular dynamics simulations

Feng

Han

et al. 2017

Oncotarget

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“…The deregulation of kinase activity is oncogenic and results in the spread of cancer cells 17,18 . The overexpression of aurora Kinase, c‐MeT kinase, polo like kinase 4 and tumour suppressor protein (p53) results in cancer 19‐22 . Computational biology and cytotoxic assay play a major role in designing drug molecules.…”

Section: Introductionmentioning

confidence: 99%

Vibrational, spectroscopic, chemical reactivity, molecular docking and in vitro anticancer activity studies against A549 lung cancer cell lines of 5‐Bromo‐indole‐3‐carboxaldehyde

S¹,

A²,

Kaviyarasu

2020

J of Molecular Recognition

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Spectroscopic investigations are performed for 5‐Bromo‐1H‐indole‐carboxaldehyde by using experimental (FT‐IR, FT‐Raman) and theoretical (DFT) calculations. Vibrational assignments of the fundamental modes were assigned on the basis of Potential energy distribution (PED) calculations. Electron Localization Function (ELF) and Local Orbital Localizer (LOL) studies were performed to visualize the electron delocalization in the molecule. Frontier molecular orbitals (FMOs) and related molecular properties were computed. The electron‐hole distribution of the molecule was also computed using Multiwfn 3.3.9 software to predict the charge transfer within the molecule. The total and partial density of states (TDOS and PDOS) and also the overlap population density of states (OPDOS) spectra were simulated. UV‐Vis spectrum of the compound was also recorded. The reactive sites of the compound were studied from the MEP and Fukui function analysis. The charge delocalization and stability of the title molecule were investigated using natural bond orbital (NBO) analysis. The lung cancer activity of the title compound against p53 tumor suppressor proteins was studied using molecular docking analysis. The in‐vitro cytotoxic activity of the molecule against human pulmonary lung cancer cell lines (A549) was determined by MTT assay.

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“…In previous study, we reported spiro [indoline-3, 4′-piperidine]-2-ones as anticancer agents and several compounds showed stronger inhibition on tyrosine kinase 16 . In this study, we designed aminopyridine-containing spiro [indoline-3, 4′-piperidine] derivatives A1-A4 using neratinib and spiro [indoline-3, 4′-piperidine]-2-one compound ( a ) patented as lead structure, then replaced piperidine with cyclopropane to obtained B1-B7 and replaced indoline with benzmorpholine to get C1-C4 (Figure 1 and Tables 1–3).…”

Section: Introductionmentioning

confidence: 99%

Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors

Zhao

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Neratinib is an oral pan HER inhibitor, that irreversibly inhibits EGFR and HER2 and was proven to be effective against multiple EGFR mutations. In previous study, we reported spiro [indoline-3, 4′-piperidine]-2-ones as anticancer agents. In this study, we designed aminopyridine-containing spiro [indoline-3,4′-piperidine] derivatives A1-A4 using Neratinib and spiro [indoline-3, 4′-piperidine]-2-one compound patented as lead structure, then replaced piperidine with cyclopropane to obtain B1-B7 and replaced indoline with benzmorpholine to get C1-C4 and D1-D2 . We synthesized these compounds and evaluated their residual activities under 0.5 M drug concentration on EGFR and ERBB2. Most of compounds showed stronger inhibition on EGFR-wt and ERBB2, in which A1-A4 showed excellent inhibitory activity with inhibition percentage on EGFR-wt kinase of 7%, 6%, 19%, 27%, respectively and 9%, 5%, 12%, 34% on ERBB2 kinase compared with 2% and 6% of Neratinib.

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Design, synthesis and molecular docking studies of some novel spiro[indoline-3, 4′-piperidine]-2-ones as potential c-Met inhibitors

Cited by 33 publications

References 16 publications

Germacrone derivatives: synthesis, biological activity, molecular docking studies and molecular dynamics simulations

Germacrone derivatives: synthesis, biological activity, molecular docking studies and molecular dynamics simulations

Vibrational, spectroscopic, chemical reactivity, molecular docking and in vitro anticancer activity studies against A549 lung cancer cell lines of 5‐Bromo‐indole‐3‐carboxaldehyde

Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors

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