Benzotriazole-oxadiazole hybrid Compounds: Synthesis, anticancer Activity, molecular docking and ADME profiling studies

Mermer, Arif; Bülbül, Muhammet Volkan; Kalender, Semiha Mervenur; Keskin, İlknur; Tüzün, Burak; Eyüpoğlu, Ozan Emre

doi:10.1016/j.molliq.2022.119264

Cited by 28 publications

(11 citation statements)

References 51 publications

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“…Analyzing the physicochemical properties of the developed drug hits is a crucial step in analyzing and determining their drug-likeness potential ( Table S3 , from Supplementary Materials ). For this reason, we evaluated the drug-likeness potential of compounds 7 and 13 through computing various descriptors, such as molar mass of molecules (mol_MW), dipole moment (dipole), total solvent accessible surface area (SASA), volume, donorHB (given hydrogen bond), accptHB (accepted hydrogen bond), globularity descriptor (glob), predicted polarizability (QPpolrz), brain−blood (QPPMDCK) and intestinal−blood (QPPCaco) barriers of molecules, predicted skin permeability (QPlogKp), and number of likely metabolic reactions (#metab) ( Table 5 ) [ 43 , 44 , 45 ] according to the Lipinski’s rule of five [ 46 , 47 ] and Jorgensen’s rule of three [ 48 ]. Molecular weights of the title compounds ranged from 485.58 to 564.48 Da, with compounds 7 and 13 having molecular weights less than 500 Da and obeying the first Lipinski rule for effective and safe drug delivery.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives

et al. 2023

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In this work, a novel series of pyridazinone derivatives (3–17) were synthesized and characterized by NMR (1H and 13C), FT-IR spectroscopies, and ESI-MS methods. All synthesized compounds were screened for their antibacterial activities against Staphylococcus aureus (Methicillin-resistant), Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, and Acinetobacter baumannii. Among the series, compounds 7 and 13 were found to be active against S. aureus (MRSA), P. aeruginosa, and A. baumannii with the lowest MIC value range of 3.74–8.92 µM. Afterwards, DFT calculations of B3LYP/6-31++G(d,p) level were carried out to investigate geometry structures, frontier molecular orbital, molecular electrostatic potential maps, and gap energies of the synthesized compounds. In addition, the activities of these compounds against various bacterial proteins were compared with molecular-docking calculations. Finally, ADMET studies were performed to investigate the possibility of using of the target compounds as drugs.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives

et al. 2023

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“…Indeed, it is of great importance to predict the movements of the molecule in human metabolism. Also, there is a situation involving many processes such as Absorption, Distribution, Metabolism, Excretion and Toxicity by the human metabolism of molecules [30] . It should be predicted whether it can be used as a drug in human metabolism by examining the movements of the molecules.…”

Section: Resultsmentioning

confidence: 99%

“…Also, there is a situation involving many processes such as Absorption, Distribution, Metabolism, Excretion and Toxicity by the human metabolism of molecules. [30] It should be predicted whether it can be used as a drug in human metabolism by examining the movements of the molecules. For this purpose, ADME/T analysis of molecules was performed.…”

Section: Molecular Dockingmentioning

confidence: 99%

Novel Quinazolinone Derivatives: Potential Synthetic Analogs for the Treatment of Glaucoma, Alzheimer's Disease and Diabetes Mellitus

Tokalı,

Taslimi,

Tuzun

et al. 2023

Chemistry & Biodiversity

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Quinazolinones, which represent an important part of nitrogen‐containing six‐membered heterocyclic compounds, are frequently used in drug design due to their wide biological activity properties. Therefore, the novel quinazolinones were synthesized from the reaction of acylated derivatives of 4‐hydroxy benzaldehyde with 3‐amino‐2‐alkylquinazolin‐4(3H)‐ones with good yields (85–94 %) and their structures were characterized using Fourier‐transform Infrared (FT‐IR), Nuclear Magnetic Resonance (1H‐NMR, 13C‐NMR), and High‐Resolution Mass Spectroscopy (HR‐MS). As the application of the synthesized compounds, their inhibition properties of the synthesized compounds on α‐Glucosidase (α‐Glu), Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), and Carbonic anhydrase I–II (hCA I–II) metabolic enzymes were investigated. All compounds showed inhibition at nanomolar level with the Ki values in the range of 12.73±1.26–93.42±9.44 nM for AChE, 8.48±0.92–25.84±2.59 nM for BChE, 66.17±5.16–818.06±44.41 for α‐Glu, 2.56±0.26–88.23±9.72 nM for hCA I, and 1.68±0.14–85.43±7.41 nM for hCA II. Molecular docking study was performed to understand the interactions of the most potent compounds with corresponding enzymes. Also, absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties of the compounds were investigated.

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“…It explains many chemical interactions such as Coulomb interactions, H-bonding, and Van der Waals forces that came into action during the interaction between proteins and title molecules. However, parameters such as Glide energy, Glide emodel, Glide einternal, and Glide posenum provide numerical evidence of the orientation of the title compound and proteins interaction [ 55 ].…”

Section: Resultsmentioning

confidence: 99%

Repositioning of acefylline as anti-cancer drug: Synthesis, anticancer and computational studies of azomethines derived from acefylline tethered 4-amino-3-mercapto-1,2,4-triazole

et al. 2022

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Novel azomethines derived from acefylline tethered triazole hybrids (7a-k) have been synthesized and evaluated against human liver cancer cell line (Hep G2) using MTT assay. The synthesized series of azomethines exhibited promising efficacy against liver cancer cell line. Screening of the synthesized series identified compound 7d with the least cell viability value (11.71 ± 0.39%) as the most potent anticancer agent in contrast to the reference drug acefylline (cell viability = 80 ± 3.87%). In this study, the potentials of the novel agents (7a-k) to inhibit liver cancer proteins were assessed. Subsequently, the structure-activity relationship of the potential drug candidates was assessed via ADME/T molecular screening. The cytotoxic potential of these derivatives was also investigated by hemolysis and thrombolysis. Their hemolytic and thrombolytic studies showed that all of these drugs had very low cytotoxicity and moderate clot lysis activity. Compound 7g (0.26% hemolysis) and 7k (52.1% clot lysis) were the least toxic and moderate thrombolytic agents respectively.

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Benzotriazole-oxadiazole hybrid Compounds: Synthesis, anticancer Activity, molecular docking and ADME profiling studies

Cited by 28 publications

References 51 publications

Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives

Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives

Novel Quinazolinone Derivatives: Potential Synthetic Analogs for the Treatment of Glaucoma, Alzheimer's Disease and Diabetes Mellitus

Repositioning of acefylline as anti-cancer drug: Synthesis, anticancer and computational studies of azomethines derived from acefylline tethered 4-amino-3-mercapto-1,2,4-triazole

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