Synthesis, antimicrobial activity, density functional modelling and molecular docking with COVID-19 main protease studies of benzoxazole derivative: 2-(p-chloro-benzyl)-5-[3-(4-ethly-1-piperazynl) propionamido]-benzoxazole

Zeyrek, Celal Tuğrul; Arpacı, Özlem Temiz; Arısoy, Mustafa; Onurdağ, Fatma Kaynak

doi:10.1016/j.molstruc.2021.130413

Cited by 12 publications

(4 citation statements)

References 33 publications

(25 reference statements)

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“…The other hits were Temafloxacin and Trovafloxacin, predicted to be potent 3CLpro ligands ( Gimeno et al, 2020 ) and experimentally shown to inhibit virus replication ( Krieg et al, 2006 ; Mirmotalebioshi et al, 2021 ) and anti-inflammatory drugs Benoxaprofen and Ciproflaxin predicted to target 3CLpro ( Marciniec et al, 2020 ; Zeyrek et al, 2021 ) as well.…”

Section: Resultsmentioning

confidence: 99%

A multi-reference poly-conformational method for in silico design, optimization, and repositioning of pharmaceutical compounds illustrated for selected SARS-CoV-2 ligands

Alexandrov¹,

Kirpich

Kantidze³

et al. 2022

PeerJ

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Background This work presents a novel computational multi-reference poly-conformational algorithm for design, optimization, and repositioning of pharmaceutical compounds. Methods The algorithm searches for candidates by comparing similarities between conformers of the same compound and identifies target compounds, whose conformers are collectively close to the conformers of each compound in the reference set. Reference compounds may possess highly variable MoAs, which directly, and simultaneously, shape the properties of target candidate compounds. Results The algorithm functionality has been case study validated in silico, by scoring ChEMBL drugs against FDA-approved reference compounds that either have the highest predicted binding affinity to our chosen SARS-CoV-2 targets or are confirmed to be inhibiting such targets in-vivo. All our top scoring ChEMBL compounds also turned out to be either high-affinity ligands to the chosen targets (as confirmed in separate studies) or show significant efficacy, in-vivo, against those selected targets. In addition to method case study validation, in silico search for new compounds within two virtual libraries from the Enamine database is presented. The library’s virtual compounds have been compared to the same set of reference drugs that we used for case study validation: Olaparib, Tadalafil, Ergotamine and Remdesivir. The large reference set of four potential SARS-CoV-2 compounds has been selected, since no drug has been identified to be 100% effective against the virus so far, possibly because each candidate drug was targeting only one, particular MoA. The goal here was to introduce a new methodology for identifying potential candidate(s) that cover multiple MoA-s presented within a set of reference compounds.

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Section: Resultsmentioning

confidence: 99%

A multi-reference poly-conformational method for in silico design, optimization, and repositioning of pharmaceutical compounds illustrated for selected SARS-CoV-2 ligands

Alexandrov¹,

Kirpich

Kantidze³

et al. 2022

PeerJ

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“…The HOMO, LUMO and total energies of the relatively active synthesized compounds were obtained from the DFT computation. Then, the other related parameters were calculated with the respective formulas (Table 5) (Zeyrek et al, 2021;Arslan et al, 2023).…”

Section: Dft Studiesmentioning

confidence: 99%

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights

Saeed,

Shahzadi,

Zahoor

et al. 2024

Front. Chem.

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Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a‒g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a‒g) as inhibitors of HCV serine protease and as antibacterial agents against B. subtilis QB-928 and E. coli AB-274. Theophylline-1,2,4-triazoles were obtained in good to excellent yields (69%–95%) in a shorter time than conventional approach. 4-Chlorophenyl moiety containing theophylline-1,2,4-triazole 4c displayed significantly higher inhibitory activity against HCV serine protease enzyme (IC50 = 0.015 ± 0.25 mg) in comparison to ribavirin (IC50 = 0.165 ± 0.053 mg), but showed excellent binding affinity (−7.55 kcal/mol) with the active site of serine protease, better than compound 4c (−6.90 kcal/mol) as well as indole-based control compound 5 (−7.42 kcal/mol). In terms of percentage inhibition of serine protease, 2-chlorophenyl compound 4b showed the maximum percentage inhibition (86%), more than that of the 3,4-dichlorophenyl compound 4c (76%) and ribavirin (81%). 3,4-Dimethylphenyl-based theophylline-1,2,4-triazole 4g showed the lowest minimum inhibitory concentration (MIC = 0.28 ± 0.50 μg/mL) against the B. subtilis bacterial strain as compared to the standard drug penicillin (MIC = 1 ± 1.50 μg/mL). The other 4-methylphenyl theophylline-1,2,4-triazole 4e (MIC = 0.20 ± 0.08 μg/mL) displayed the most potent antibacterial potential against E. coli in comparison to the standard drug penicillin (MIC = 2.4 ± 1.00 μg/mL). Molecular docking studies further helped in an extensive understanding of all of the interactions between compounds and the enzyme active site, and DFT studies were also employed to gain insights into the molecular structure of the synthesized compounds. The results indicated that theophylline-linked triazole derivatives 4b and 4c showed promise as leading contenders in the fight against the HCV virus. Moreover, compounds 4e and 4g demonstrated potential as effective chemotherapeutic agents against E. coli and B. subtilis, respectively. To substantiate these findings, additional in vivo studies and clinical trials are imperative, laying the groundwork for their integration into future drug design and development.

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“…Heteroallenesisothiocyanatesareaninterestinggroupoforganiccompounds that are used asreactivekeyprecursors in the synthesis of heterocyclic molecules due to theirdiversereactionsandalsoto the ireasyavailability. [1][2][3][4] Isothiocyanatesare often prepared from thereactionofaminederivativeswithcarbondisulfide [5][6][7][8]orthiophosgene, [9][10][11] as well as treatmentofthecarboxylicacidderivativeswithammoniumthiocyantes [12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Facile synthesis of quinazoline, oxazine and triazole derivatives as potential antimi-crobial agents based on isothiocyanate moiety

Ahmed

El-karim

Behalo

2022

Benha Journal of Applied Sciences

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Synthesis, antimicrobial activity, density functional modelling and molecular docking with COVID-19 main protease studies of benzoxazole derivative: 2-(p-chloro-benzyl)-5-[3-(4-ethly-1-piperazynl) propionamido]-benzoxazole

Cited by 12 publications

References 33 publications

A multi-reference poly-conformational method for in silico design, optimization, and repositioning of pharmaceutical compounds illustrated for selected SARS-CoV-2 ligands

A multi-reference poly-conformational method for in silico design, optimization, and repositioning of pharmaceutical compounds illustrated for selected SARS-CoV-2 ligands

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights

Facile synthesis of quinazoline, oxazine and triazole derivatives as potential antimi-crobial agents based on isothiocyanate moiety

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