Semi-Synthesis of N-Aryl Amide Analogs of Piperine from Piper nigrum and Evaluation of Their Antitrypanosomal, Antimalarial, and Anti-SARS-CoV-2 Main Protease Activities

Wansri, Rattanaporn; Lin, Aye Chan Khine; Pengon, Jutharat; Kamchonwongpaisan, Sumalee; Srimongkolpithak, Nitipol; Rattanajak, Roonglawan; Wilasluck, Patcharin; Deetanya, Peerapon; Wangkanont, Kittikhun; Hengphasatporn, Kowit; Shigeta, Yasuteru; Liangsakul, Jatupol; Suroengrit, Aphinya; Boonyasuppayakorn, Siwaporn; Chuanasa, Taksina; De-Eknamkul, Wanchai; Hannongbua, Supot; Rungrotmongkol, Thanyada; Chamni, Supakarn

doi:10.3390/molecules27092841

Cited by 14 publications

(12 citation statements)

References 50 publications

(61 reference statements)

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“…A native-terminated SARS-CoV-2 M pro was produced using a previously reported procedure for producing a native-terminated SARS-CoV-1 M pro 47 . The protease activity and inhibition assays were performed as described in previous studies 6 , 21 , 48 .…”

Section: Methodsmentioning

confidence: 99%

Promising SARS-CoV-2 main protease inhibitor ligand-binding modes evaluated using LB-PaCS-MD/FMO

Hengphasatporn

Harada

Wilasluck

et al. 2022

Sci Rep

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Parallel cascade selection molecular dynamics-based ligand binding-path sampling (LB-PaCS-MD) was combined with fragment molecular orbital (FMO) calculations to reveal the ligand path from an aqueous solution to the SARS-CoV-2 main protease (Mpro) active site and to customise a ligand-binding pocket suitable for delivering a potent inhibitor. Rubraxanthone exhibited mixed-inhibition antiviral activity against SARS-CoV-2 Mpro, relatively low cytotoxicity, and high cellular inhibition. However, the atomic inhibition mechanism remains ambiguous. LB-PaCS-MD/FMO is a hybrid ligand-binding evaluation method elucidating how rubraxanthone interacts with SARS-CoV-2 Mpro. In the first step, LB-PaCS-MD, which is regarded as a flexible docking, efficiently samples a set of ligand-binding pathways. After that, a reasonable docking pose of LB-PaCS-MD is evaluated by the FMO calculation to elucidate a set of protein–ligand interactions, enabling one to know the binding affinity of a specified ligand with respect to a target protein. A possible conformation was proposed for rubraxanthone binding to the SARS-CoV-2 Mpro active site, and allosteric inhibition was elucidated by combining blind docking with k-means clustering. The interaction profile, key binding residues, and considerable interaction were elucidated for rubraxanthone binding to both Mpro sites. Integrated LB-PaCS-MD/FMO provided a more reasonable complex structure for ligand binding at the SARS-CoV-2 Mpro active site, which is vital for discovering and designing antiviral drugs.

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Section: Methodsmentioning

confidence: 99%

Promising SARS-CoV-2 main protease inhibitor ligand-binding modes evaluated using LB-PaCS-MD/FMO

Hengphasatporn

Harada

Wilasluck

et al. 2022

Sci Rep

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“…Among these, the most important are alkaloids and amides, which have excellent biological activities, such as anticancer activity. In the species P. nigrum L., only 20% of its compounds have been characterized [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Antimicrobial Activity and Cytotoxicity Effects of Extracts of Piper nigrum L. and Piperine

et al. 2022

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P. nigrum L. extracts and the piperine alkaloid have important antimicrobial, anti-inflammatory, and antioxidant properties. Therefore, in this study, we evaluated the antimicrobial activity and cytotoxicity of P. nigrum L. extracts and piperine, a compound isolated from the extracts of P. nigrum L. Extracts obtained via maceration, soxhlet, and purification steps, in addition to isolated piperine, were used in this study. Spectroscopic methods, such as nuclear magnetic resonance, scanning electron microscopy, X-ray diffraction, thermogravimetry, and differential scanning calorimetry, were used to characterize piperine. In the microbiological analyses, the extract obtained via maceration-derived sample showed high efficiency in inhibiting Salmonella spp. (MIC < 100 μg/mL). The extract obtained via a soxhlet-derived sample showed promising inhibitory activity against almost all microorganisms, with negligible inhibition of Pseudomonas aeruginosa. Favorable inhibition coefficients were also observed against Staphylococcus aureus and Salmonella spp. (MIC < 100 μg/mL) for the extract obtained via purification of the steps-derived sample. Piperine showed an excellent inhibition coefficient against most microorganisms, with inactivity only observed against P. aeruginosa. Cytotoxicity evaluation assays in cancer cell lines revealed that piperine exhibited inhibitory potential on all tested tumor cell lines, causing a decrease in cell viability and achieving an IC50 of less than 30 μg/mL. The analyzed extracts from P. nigrum L. seeds showed cytotoxic activity against tumor and non-tumor cell lines.

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“…The cytotoxicity of the active compounds was tested with Vero E6 cell lines (Wansri et al). 80 Results were reported as means and SEM of three independent experiments. 4.7.…”

Section: Virtual Screening By Drug-likeness Analysismentioning

confidence: 99%

Identification of Promising Sulfonamide Chalcones as Inhibitors of SARS-CoV-2 3CL^pro through Structure-Based Virtual Screening and Experimental Approaches

Pojtanadithee,

Hengphasatporn,

Suroengrit

et al. 2023

J. Chem. Inf. Model.

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3CLpro is a viable target for developing antiviral therapies against the coronavirus. With the urgent need to find new possible inhibitors, a structure-based virtual screening approach was developed. This study recognized 75 pharmacologically bioactive compounds from our in-house library of 1052 natural product-based compounds that satisfied drug-likeness criteria and exhibited good bioavailability and membrane permeability. Among these compounds, three promising sulfonamide chalcones were identified by combined theoretical and experimental approaches, with SWC423 being the most suitable representative compound due to its competitive inhibition and low cytotoxicity in Vero E6 cells (EC50 = 0.89 ± 0.32 μM; CC50 = 25.54 ± 1.38 μM; SI = 28.70). The binding and stability of SWC423 in the 3CLpro active site were investigated through all-atom molecular dynamics simulation and fragment molecular orbital calculation, indicating its potential as a 3CLpro inhibitor for further SARS-CoV-2 therapeutic research. These findings suggested that inhibiting 3CLpro with a sulfonamide chalcone such as SWC423 may pave the effective way for developing COVID-19 treatments.

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Semi-Synthesis of N-Aryl Amide Analogs of Piperine from Piper nigrum and Evaluation of Their Antitrypanosomal, Antimalarial, and Anti-SARS-CoV-2 Main Protease Activities

Cited by 14 publications

References 50 publications

Promising SARS-CoV-2 main protease inhibitor ligand-binding modes evaluated using LB-PaCS-MD/FMO

Promising SARS-CoV-2 main protease inhibitor ligand-binding modes evaluated using LB-PaCS-MD/FMO

Evaluation of Antimicrobial Activity and Cytotoxicity Effects of Extracts of Piper nigrum L. and Piperine

Identification of Promising Sulfonamide Chalcones as Inhibitors of SARS-CoV-2 3CL^pro through Structure-Based Virtual Screening and Experimental Approaches

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Semi-Synthesis of N-Aryl Amide Analogs of Piperine from Piper nigrum and Evaluation of Their Antitrypanosomal, Antimalarial, and Anti-SARS-CoV-2 Main Protease Activities

Cited by 14 publications

References 50 publications

Promising SARS-CoV-2 main protease inhibitor ligand-binding modes evaluated using LB-PaCS-MD/FMO

Promising SARS-CoV-2 main protease inhibitor ligand-binding modes evaluated using LB-PaCS-MD/FMO

Evaluation of Antimicrobial Activity and Cytotoxicity Effects of Extracts of Piper nigrum L. and Piperine

Identification of Promising Sulfonamide Chalcones as Inhibitors of SARS-CoV-2 3CLpro through Structure-Based Virtual Screening and Experimental Approaches

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Product

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Identification of Promising Sulfonamide Chalcones as Inhibitors of SARS-CoV-2 3CL^pro through Structure-Based Virtual Screening and Experimental Approaches