WITHDRAWN: New picolinic acid derivatives: Synthesis, docking study and anti-EGFR kinase inhibitory effect

Abbas, Ali H.; Mahmood, Ammar A. Razzak; Tahtamouni, Lubna H.; Al-Mazaydeh, Zainab A.; Rammaha, Majdoleen S.; Alsoubani, Fatima; Al-bayati, Rheda I.

doi:10.1016/j.matpr.2021.05.354

Cited by 3 publications

(2 citation statements)

References 28 publications

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“…It has been reported that the accuracy of docking studies can vary between 0-92% (Chen 2014). Our recently published work (Abbas et al 2021) showed that compound (4C) that gave a low ΔG score (when compared to the other tested compounds including erlotinib) in EGFR kinase molecular docking studies was the most potent cytotoxic compound and its cytotoxicity was mediated via inhibition of EGFR kinase when studied in vitro.…”

Section: A) B)mentioning

confidence: 99%

A novel derivative of picolinic acid induces endoplasmic reticulum stress-mediated apoptosis in human non-small cell lung cancer cells: synthesis, docking study, and anticancer activity

Abbas¹,

Mahmood²,

Tahtamouni³

et al. 2021

PHAR

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Thirteen new derivatives of picolinic acid (4–7) were designed and synthesized from the starting parent molecule, picolinic acid. The new compounds were characterized by ATR-FTIR, 1HNMR, and CHNS analysis. A molecular docking study was performed to evaluate the binding affinity of the synthesized compounds toward EGFR kinase domain that indicated occupation of the critical site of EGFR kinase pocket and excellent positioning of the compounds in the pocket. The cytotoxic activity of the compounds against two human cancer cell lines (A549 and MCF-7), the non-tumorigenic MCF10A cell line, and white blood cells (WBC) was evaluated using the MTT assay. Compound 5 showed anticancer activity against A549 lung cancer cells (IC50 = 99.93 µM) but not against MCF-7 breast cancer cells or normal cells. Compound 5 mediated cytotoxicity in A549 lung cancer cells by inducing apoptotic cell death, as suggested by fragmented nuclei after DAPI staining, and agarose gel electrophoresis. Moreover, compound 5 triggered the activation of caspases 3, 4 and 9. However, compound 5 treatment did not affect the release of cytochrome c from the mitochondria to the cytosol, as compared to the vehicle-treated control cells. Nevertheless, compound 5-treated cells reported greater release of smac/DIABLO to the cytosol. In the same context, both compound 5 and thapsigargin (specific inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA)) enhanced eIF2 phosphorylation, reflecting the activation of the atypical ER stress pathway and the potential applicability of compound 5 in lung cancer treatment.

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Section: A) B)mentioning

confidence: 99%

A novel derivative of picolinic acid induces endoplasmic reticulum stress-mediated apoptosis in human non-small cell lung cancer cells: synthesis, docking study, and anticancer activity

Abbas¹,

Mahmood²,

Tahtamouni³

et al. 2021

PHAR

Self Cite

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“…synthesised new compounds and evaluated their anti-tumour activity against MCF-7, A549 and their cytotoxicity against normal cells (MCF10A and WBC). Compound 41 ( Figure 3 ) exhibited anti-tumour activity against MCF-7 cells (GI 50 = 86.8 µg/mL), but not against A549, MCF10A and WBC cells 48 .…”

Section: Oxadiazolementioning

confidence: 99%

Research progress on the synthesis and pharmacology of 1,3,4-oxadiazole and 1,2,4-oxadiazole derivatives: a mini review

Wang

Sun

Jia

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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Oxadiazole is a five-membered heterocyclic compound containing two nitrogen atoms and one oxygen atom. The 1,3,4-oxadiazole and 1,2,4-oxadiazole have favourable physical, chemical, and pharmacokinetic properties, which significantly increase their pharmacological activity via hydrogen bond interactions with biomacromolecules. In recent years, oxadiazole has been demonstrated to be the biologically active unit in a number of compounds. Oxadiazole derivatives exhibit antibacterial, anti-inflammatory, anti-tuberculous, anti-fungal, anti-diabetic and anticancer activities. In this paper, we report a series of compounds containing oxadiazole rings that have been published in the last three years only (2020–2022) as there was no report or their activities described in any article in 2019, which will be useful to scientists in research fields of organic synthesis, medicinal chemistry, and pharmacology.

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Virtual screening, XGBoost based QSAR modelling, Molecular Docking and Molecular Dynamics Simulation approach to discover a new inhibitor targeting ErbB1 Protein

Bouchama,

Kraim,

Brahimi

et al. 2024

Preprint

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ErbB1 is a protein found on certain types of human cells that binds to a substance called epidermal growth factor (EGFR). The ErbB1 protein is involved in cell signalling pathways that control cell division, proliferation, and survival. Sometimes, mutations in the EGFR gene cause ErbB1 proteins to be made in higher-than-normal amounts on some types of cancer cells. The aim of this study is using the virtual screening based on ligand and structure drug design using respectively QSAR, molecular docking & molecular dynamics simulations approaches to identify novel antitumor small molecules. Therefore, the QSAR model was developed and validated using XGBOOST as a learning algorithm classifier trained on 5215 compounds. The validated model is used for screening of more than 80k natural products downloaded and prepared from the ZINC database to offer us only 36 as potent predicted inhibitors against ErbB1. The selected active compounds were docked against the target represented by the PDB ID: 3POZ. The obtained top five scoring compounds were compared to the reference ligand TAK285, to the Lapatinib and the Erlotinib drugs, after this phase their stability into the ErbB1 protein binding site has been validated using the molecular dynamics simulation.

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WITHDRAWN: New picolinic acid derivatives: Synthesis, docking study and anti-EGFR kinase inhibitory effect

Cited by 3 publications

References 28 publications

A novel derivative of picolinic acid induces endoplasmic reticulum stress-mediated apoptosis in human non-small cell lung cancer cells: synthesis, docking study, and anticancer activity

A novel derivative of picolinic acid induces endoplasmic reticulum stress-mediated apoptosis in human non-small cell lung cancer cells: synthesis, docking study, and anticancer activity

Research progress on the synthesis and pharmacology of 1,3,4-oxadiazole and 1,2,4-oxadiazole derivatives: a mini review

Virtual screening, XGBoost based QSAR modelling, Molecular Docking and Molecular Dynamics Simulation approach to discover a new inhibitor targeting ErbB1 Protein

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