Novel 1,2,3-Triazole Erlotinib Derivatives as Potent IDO1 Inhibitors: Design, Drug-Target Interactions Prediction, Synthesis, Biological Evaluation, Molecular Docking and ADME Properties Studies

Xu, Guiqing; Gong, Xiaoqing; Zhu, Yingying; Yao, Xiaojun; Peng, Lizeng; Yang, Juan; Mao, Longfei

doi:10.3389/fphar.2022.854965

Cited by 10 publications

(5 citation statements)

References 31 publications

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Section: Methodsmentioning

confidence: 99%

“…It also predicted molecular weight of the compounds, predicted octanol/water partition coefficient (QP log P o/w ), determine aqueous solubility of compounds (QP log S), Predicted brain/blood partition coefficient (QPlogBB), predicted apparent Caco-2 cell permeability in nm s −1 (QPPCaco), predicted IC50 value for blockage of HERG K+ channels (QPlogHERG) and predicted value of binding to human serum albumin (QP log K hsa ). 40 2.13. Extraction of RNA and quantitative gene analysis of QS genes in P. aeruginosa Total RNA of EMB25 culture was isolated from the stationary phase grown for 24 h in presence and absence of organic extract using RNeasy® Mini Kit (Qiagen) as per the protocol mentioned in the kit.…”

Section: Computational Studiesmentioning

confidence: 99%

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Inhibition and eradication of Pseudomonas aeruginosa biofilms by secondary metabolites of Nocardiopsis lucentensis EMB25

et al. 2023

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Section: Methodsmentioning

confidence: 99%

Section: Computational Studiesmentioning

confidence: 99%

Inhibition and eradication of Pseudomonas aeruginosa biofilms by secondary metabolites of Nocardiopsis lucentensis EMB25

et al. 2023

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“…2 , 1) or icotinib (Fig. 2 , 2), yielding derivatives with significant IDO1 inhibition activity 14 , 15 . These compounds possess two or more pharmacophores, enabling them to interact with multiple targets in tumor cells simultaneously.…”

Section: Introductionmentioning

confidence: 99%

Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation

Gao,

Wang,

Fan

et al. 2024

Sci Rep

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A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC50 value of 3.94 ± 0.17 µmol L−1 (NCI-H1299), 3.16 ± 0.11 µmol L−1 (A549), and 1.83 ± 0.13 µmol L−1 (NCI-H1437) for 7a, and an IC50 value of 3.84 ± 0.22 µmol L−1 (NCI-H1299), 3.86 ± 0.38 µmol L−1 (A549), and 1.69 ± 0.25 µmol L−1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer.

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“…For example, five erlotinib-conjugated 1,2,3-triazole derivatives were designed using a structure-based drug design strategy to explore novel IDO1 inhibitors. Among them, compound e with an o-bromobenzyl structure on the triazole ring showed the best IDO1 inhibitory activity (IC 50 = 0.32 ± 0.07 μM) [ 18 ]. In another study, the anti-HIV drug cabotegravir was modified by introducing a 1,2,3-triazole moiety to obtain compounds KJ1–KJ19.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives

Liu,

Gao

et al. 2024

Molecules

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In this study, 14 structurally novel gefitinib-1,2,3-triazole derivatives were synthesized using a click chemistry approach and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). Preliminary cell counting kit-8 results showed that most of the compounds exhibit excellent antitumor activity against epidermal growth factor receptor wild-type lung cancer cells NCI-H1299, A549 and NCI-H1437. Among them, 4b and 4c showed the most prominent inhibitory effects. The half maximal inhibitory concentration (IC50) values of 4b were 4.42 ± 0.24 μM (NCI-H1299), 3.94 ± 0.01 μM (A549) and 1.56 ± 0.06 μM (NCI-1437). The IC50 values of 4c were 4.60 ± 0.18 µM (NCI-H1299), 4.00 ± 0.08 μM (A549) and 3.51 ± 0.05 μM (NCI-H1437). Furthermore, our results showed that 4b and 4c could effectively inhibit proliferation, colony formation and cell migration in a concentration-dependent manner, as well as induce apoptosis in H1299 cells. In addition, 4b and 4c exerted its anti-tumor effects by inducing cell apoptosis, upregulating the expression of cleaved-caspase 3 and cleaved-PARP and downregulating the protein levels of Bcl-2. Based on these results, it is suggested that 4b and 4c be developed as potential new drugs for lung cancer treatment.

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Novel 1,2,3-Triazole Erlotinib Derivatives as Potent IDO1 Inhibitors: Design, Drug-Target Interactions Prediction, Synthesis, Biological Evaluation, Molecular Docking and ADME Properties Studies

Abstract: Graphical Abstract

Cited by 10 publications

References 31 publications

Inhibition and eradication of Pseudomonas aeruginosa biofilms by secondary metabolites of Nocardiopsis lucentensis EMB25

Inhibition and eradication of Pseudomonas aeruginosa biofilms by secondary metabolites of Nocardiopsis lucentensis EMB25

Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation

Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives

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