Dithiocarbamates and dithiocarbonates containing 6-nitrosaccharin scaffold: Synthesis, antimycobacterial activity and in silico target prediction using ensemble docking-based reverse virtual screening

Trawally, Muhammed; Demir-Yazıcı, Kübra; Dingiş-Birgül, Serap İpek; Kaya, Kerem; Akdemir, Atilla; Güzel-Akdemir, Özlen

doi:10.1016/j.molstruc.2022.134818

Cited by 7 publications

(4 citation statements)

References 56 publications

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“…Li et al 39 selected 7769 protein-ligand complexes from the PDBbind database (version 2018) as the structure pool to evaluate the performance of 4 classical docking programs. In 2023, Trawally et al 55 conducted reverse docking to understand the mechanism of action of a potent antimycobacterial compound 6g. The protein database consists of nine putative targets with fifteen different experimental structures.…”

Section: Discussionmentioning

confidence: 99%

Benchmarking Reverse Docking through AlphaFold2 Human Proteome

Luo,

Wang,

et al. 2023

Preprint

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Predicting binding of a small molecule to the human proteome by reverse docking methods, we can predict the target interactions of drug compounds in the human body, as well as further evaluate their potential off-target effects or toxic side effects. In this study, we constructed 11 pipelines to evaluate and benchmark thoroughly the predictive capabilities of these reverse docking pipelines. The pipelines were built using site prediction tools (PointSite and SiteMap) based on the AF2 human proteome, docking programs (Glide and AutoDock Vina), and scoring functions (Glide, Autodock Vina, RTMScore, DeepRMSD, OnionNet-SFCT). The results show that pipeline glide_sfct (PS) exhibited the best target prediction ability and successfully predicted the similar proteins of native targets. This finding provides important clues for understanding the promiscuity between the drug ligand and the whole human proteome. In general, our study has the potential to increase the success rate and reduce the development timeline of drug discovery, thereby saving costs.

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Section: Discussionmentioning

confidence: 99%

Benchmarking Reverse Docking through AlphaFold2 Human Proteome

Luo,

Wang,

et al. 2023

Preprint

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“…Ligands with lengths of ≤ 20 Å were allowed to dock. Conformational flexibility was allowed for hydroxyl groups of amino acid residues located within 5 Å of co-crystallized ligands and are not involved in the protein hydrogen bonding network [39].…”

Section: Protein Preparation and Receptor Grid Generation Structuresmentioning

confidence: 99%

“…Docking studies were conducted using the Glide module with Extra Precision (XP) employing the default settings. The planarity of the conjugated π groups was improved, docking penalties based on the Epik state were implemented, and each ligand was docked 25 times to produce the 3 best poses [39].…”

Section: Molecular Dockingmentioning

confidence: 99%

Antiviral Properties of 5‑Sulfamoyl‑1H‑Indole-Linked Spirothiazolidinone Derivatives: A Study on Human Parainfluenza Virus-2

TRAWALLY,

YILMAZ,

ÇELİK

et al. 2024

jrp

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Human parainfluenza viruses (HPIVs) are responsible for a wide range of respiratory infections in humans, particularly in children, the elderly, and immunocompromised individuals. This paper presents a study regarding the antiviral activity of a series of 3-phenyl-5-sulfamoyl-N-(7/8/9-(non)substituted-3-oxo-1-thia-4azaspiro[4.4]non/[4.5]dec-4-yl)-1H-indole-2-carboxamide derivatives against HPIV-2. Our findings suggest the compounds displayed low potency against HPIV-2. Compounds 4 and 8 exhibited the most potent antiviral effects with inhibition of 95.46 and 90.90 % at 10 mg/mL, respectively. Molecular modeling studies were conducted on hemagglutinin-neuraminidase, a crucial druggable target for HPIV, to predict the binding modes of the compounds.

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“…As we clearly stated in our previous publication, all molecular dynamics simulations were performed using the Desmond tool (Trawally et al, 2023).…”

Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

Synthesis of flurbiprofen thiadiazole urea derivatives and assessment of biological activities and molecular docking studies

Zengin Kurt,

Altundağ,

Tokgöz

et al. 2023

Chem Biol Drug Des

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Totally 15 novel flurbiprofen urea derivatives were synthesized bearing the thiadiazole ring. Their inhibition effects on tyrosinase were determined. 3c was found to be the strongest inhibitor with the IC50 value of 68.0 μM against tyrosinase. The enzyme inhibition types of the synthesized compounds were determined by examining the kinetic parameters. The inhibition type of 3c was determined as uncompetitive and the Ki value was calculated as 36.3 μM. Moreover, their cytotoxic effects on hepatocellular carcinoma (HepG2), colorectal carcinoma (HT‐29), and melanoma (B16F10) cell lines were evaluated. According to the cytotoxicity results, 3l (IC50 = 14.11 μM) showed the highest cytotoxicity on the HT‐29 cells, while 3o (IC50 = 4.22 μM) exhibited the strongest cytotoxic effect on HepG2 cell lines. Also, 3j (IC50 = 7.55 μM strongly affected B16F10. The effects of synthesized compounds on the healthy cell line were evaluated on the CCD‐986Sk cell line. Molecular modelling studies have indicated the potential binding interactions of the uncompetitive inhibitor 3c with the enzyme‐substrate complex.

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Dithiocarbamates and dithiocarbonates containing 6-nitrosaccharin scaffold: Synthesis, antimycobacterial activity and in silico target prediction using ensemble docking-based reverse virtual screening

Cited by 7 publications

References 56 publications

Benchmarking Reverse Docking through AlphaFold2 Human Proteome

Benchmarking Reverse Docking through AlphaFold2 Human Proteome

Antiviral Properties of 5‑Sulfamoyl‑1H‑Indole-Linked Spirothiazolidinone Derivatives: A Study on Human Parainfluenza Virus-2

Synthesis of flurbiprofen thiadiazole urea derivatives and assessment of biological activities and molecular docking studies

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