Synthesis, characterization of some substituted Quinolines derivatives: DFT, computational, in silico ADME, molecular docking and biological activities

Golea, Lynda; Chebaki, Rachid; Laabassi, Mohammed; Mosset, Paul

doi:10.1016/j.cdc.2022.100977

Cited by 11 publications

(4 citation statements)

References 36 publications

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“…ADME (absorption, distribution, metabolism, and elimination) calculations are essential for improving the pharmacokinetic characteristics of novel drugs [30] . The pharmacokinetic properties of the most active compounds ( 4 b , 4 c , and 4 e ) were determined using the QikProp module of Schrödinger Maestro 13.5.…”

Section: Resultsmentioning

confidence: 99%

“…In silico ADME studies ADME (absorption, distribution, metabolism, and elimination) calculations are essential for improving the pharmacokinetic characteristics of novel drugs. [30] The pharmacokinetic properties of the most active compounds (4 b, 4 c, and 4 e) were determined using the QikProp module of Schrödinger Maestro 13.5. The ADME molecular descriptors, including molecular weight, number of hydrogen bond donors and acceptors, octanol/water partition coefficient, aqueous solubility, Caco-2 cell permeability, brain/blood partition coefficient, MDCK cell permeability, and human oral absorption values, are presented in Table 3.…”

Section: Molecular Docking Analysis On Pi3k Protein Targetmentioning

confidence: 99%

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Synthesis and Anticancer Activity of Novel Derivatives of α,β‐Unsaturated Ketones Based on Oleanolic Acid: in Vitro and in Silico Studies against Prostate Cancer Cells

Şenol,

Ghaffari‐Moghaddam,

Bulut

et al. 2023

Chemistry & Biodiversity

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Herein, new derivatives of α,β‐unsaturated ketones based on oleanolic acid (4a‐i) were designed, synthesized, characterized, and tested against human prostate cancer (PC3). According to the in vitro cytotoxic study, title compounds (4a‐i) showed significantly lower toxicity toward healthy cells (HUVEC) in comparison with the reference drug doxorubicin. The compounds with the lowest IC50 values on PC3 cell lines were 4b (7.785 µM), 4c (8.869 µM), and 4e (8.765 µM). The results of the ADME calculations showed that the drug‐likeness parameters were within the defined ranges according to Lipinski’s and Jorgensen's rules. For the most potent compounds 4b, 4c, and 4e, a molecular docking analysis using the induced fit docking (IFD) protocol was performed against three protein targets (PARP, PI3K, and mTOR). Based on the IFD scores, compound 4b had the highest calculated affinity for PARP1, while compound 4c had higher affinities for mTOR and PI3K. The MM‐GBSA calculations showed that the most potent compounds had high binding affinities and formed stable complexes with the protein targets. Finally, a 50 ns molecular dynamics simulation was performed to study the behavior of protein target complexes under in silico physiological conditions.

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Section: Resultsmentioning

confidence: 99%

Section: Molecular Docking Analysis On Pi3k Protein Targetmentioning

confidence: 99%

Synthesis and Anticancer Activity of Novel Derivatives of α,β‐Unsaturated Ketones Based on Oleanolic Acid: in Vitro and in Silico Studies against Prostate Cancer Cells

Şenol,

Ghaffari‐Moghaddam,

Bulut

et al. 2023

Chemistry & Biodiversity

View full text Add to dashboard Cite

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“…Additionally, their bioavailability score of 0.55 indicated that they were more drug-like in nature. 35 In contrast, the lipophilicity behaviour was demonstrated by a consensual Log Po/w in the range of 5.44 to 3.59. Although the 4c and 4d compounds had good drug-likeness, they showed less potency.…”

Section: Predicting the Compounds' Absorption Distribution Metabolism...mentioning

confidence: 97%

Synthesis, Biological Activity, and Computational Examination of New 3-Cyano-2-oxa-pyridine Derivatives

2023

TJNPR

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3-Cyano-2-pyridones are analogous to the alkaloid ricinine, the first known alkaloid that contains a cyano group. The anticancer activity of 3-cyano-2-pyridone derivatives is exciting due to the numerous biological targets they may interact with, including phosphodiesterase 3 and the provirus integration site for the Moloney murine leukaemia virus-1 kinase and survival. 18,19 Encouraged by recent literature observations, some new pyridine derivatives were synthesised in this study, resulting in fascinating heterocyclic frameworks that are most beneficial for the construction of various chemical libraries of compounds with a variety of functional groups for examining unique biological agents. This study was aimed at synthesising new 3-cyano-2-oxa-pyridine derivatives (4a-e) using substituted acetophenone, ethyl cyanoacetate, and aryl aldehydes in the presence of ammonium acetate. Moreover, they demonstrated anticancer efficacy against two cancer cell lines, namely cerebral glioblastoma multiforme and cervical carcinoma. The variations in biological activity induced by changes in the positions of substituted groups like H, Br, NH2, and OCH3 were explored as an outcome of this research. The synthesised compounds were subjected to theoretical calculations using the density-functional theory (DFT), an adverse medical device event (AMDE) assay, and by making comparisons with experimental data. These studies will provide insight into the molecular properties of novel pyridine derivatives. Materials and Methods Sources for cell lines and maintenance of cell culturesTwo cancer cell lines, namely cerebral glioblastoma multiforme (AMGM5) and cervical carcinoma (HeLa), were purchased from the IRAQ Biotechnology Cell Banking Centre in Basrah and grown in RPMI-1640 treated with 10% foetal bovine serum, 100 units/mL of the antibiotic penicillin, and 100 g/mL of minocycline. The cells were

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“…The integration of advanced computational tools for predicting ADME properties, alongside traditional assessments like in-vivo and in-vitro evaluations, plays a crucial role in the early stages of drug development. [37,38] This study seeks to contribute to the ongoing endeavors in TB drug discovery by exploring the development, characterization, and bioefficacy assessment of ester derivatives of 6-substituted-2-chloroquinoline-3carbaldehyde hydrazide analogs. The ADME characteristics of the synthesized molecules were predicted by employing SwissADME, a web-based platform.…”

Section: Abstract a R T I C L E I N F Omentioning

confidence: 99%

Innovative Hybrid Compounds Targeting Tuberculosis: Development, Characterization and Bioefficacy analysis of 6-substituted-2-Chloroquinoline-3-Carbaldehyde Hydrazide Ester derivatives

Potdar,

Joshi

2024

Int. J. Pharm. Sci. Drug Res.

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This study delves into the biological activity of ester compounds obtained from analogues of 6-substituted-2-chloroquinoline-3-carbaldehyde hydrazide, aiming to exploit the combined antitubercular properties of quinoline and hydrazide to create innovative hybrid compounds. The molecules underwent a meticulous multi-step synthesis process, followed by purification through recrystallization. Methodologies such as 1H NMR, 13C NMR, FTIR and Mass Spectrometry was used to confirm the molecular structures of developed derivatives. SWISSADME, an online tool, was utilized to predict the ADME properties, shedding light on their pharmacokinetic profiles. Evaluation of in vitro antitubercular activity employing the Alamar blue method highlighted compounds 4a and 4f, exhibiting noteworthy efficacy achieving threshold concentrations of 6.25 µg/ml for M. tuberculosis inhibition. These findings suggest the possibility of novel quinoline Scaffold as potential molecule for TB treatment, contributing to ongoing endeavors in TB drug discovery and potentially laying the groundwork to develop effective antitubercular therapies.

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Synthesis, characterization of some substituted Quinolines derivatives: DFT, computational, in silico ADME, molecular docking and biological activities

Cited by 11 publications

References 36 publications

Synthesis and Anticancer Activity of Novel Derivatives of α,β‐Unsaturated Ketones Based on Oleanolic Acid: in Vitro and in Silico Studies against Prostate Cancer Cells

Synthesis and Anticancer Activity of Novel Derivatives of α,β‐Unsaturated Ketones Based on Oleanolic Acid: in Vitro and in Silico Studies against Prostate Cancer Cells

Synthesis, Biological Activity, and Computational Examination of New 3-Cyano-2-oxa-pyridine Derivatives

Innovative Hybrid Compounds Targeting Tuberculosis: Development, Characterization and Bioefficacy analysis of 6-substituted-2-Chloroquinoline-3-Carbaldehyde Hydrazide Ester derivatives

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