Evaluation of N-benzoylthiourea derivatives as popssible analgesic agents by predicting their hysicochemical and pharmacokinetic properties, toxicity, and analgesic activity

Hardjono, Suko; Siswandono, Siswandono; Andayani, Rina

doi:10.22146/ijbiotech.27171

Cited by 12 publications

(8 citation statements)

References 11 publications

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“…In addition, a compound is considered to have a high Caco-2 permeability if it has a P app > 8 × 10 6 cm/s. Using the pkCSM predictive model, predicted log Papp values > 0.90 cm/s indicates a high Caco-2 permeability of the compounds tested [65]. In that sense, the P app value observed for the phenolic compounds identified in the avocado peel, seed coat and seed, agrees with that absorption percentage previously discussed.…”

Section: Theoretical Absorption Percentage Of Individual Phenolic Compounds (Based On Lipinski Parameters)supporting

confidence: 82%

Phenolic-Rich Extracts from Avocado Fruit Residues as Functional Food Ingredients with Antioxidant and Antiproliferative Properties

et al. 2021

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In this study, the total phenolic compounds content and profile, the nutritional value, the antioxidant and antiproliferative activities of avocado peel, seed coat, and seed extracts were characterized. Additionally, an in-silico analysis was performed to identify the phenolic compounds with the highest intestinal absorption and Caco-2 permeability. The avocado peel extract possessed the highest content of phenolic compounds (309.95 ± 25.33 mMol GA/100 g of extract) and the lowest effective concentration (EC50) against DPPH and ABTS radicals (72.64 ± 10.70 and 181.68 ± 18.47, respectively). On the other hand, the peel and seed coat extracts had the lowest energy densities (226.06 ± 0.06 kcal/100g and 219.62 ± 0.49 kcal/100g, respectively). Regarding the antiproliferative activity, the avocado peel extract (180 ± 40 µg/mL) showed the lowest inhibitory concentration (IC50), followed by the seed (200 ± 21 µg/mL) and seed coat (340 ± 32 µg/mL) extracts. The IC50 of the extracts induced apoptosis in Caco-2 cells at the early and late stages. According to the in-silico analysis, these results could be related to the higher Caco-2 permeability to hydroxysalidroside, salidroside, sakuranetin, and luteolin. Therefore, this study provides new insights regarding the potential use of these extracts as functional ingredients with antioxidant and antiproliferative properties and as medicinal agents in diseases related to oxidative stress such as cancer.

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Section: Theoretical Absorption Percentage Of Individual Phenolic Compounds (Based On Lipinski Parameters)supporting

confidence: 82%

Phenolic-Rich Extracts from Avocado Fruit Residues as Functional Food Ingredients with Antioxidant and Antiproliferative Properties

et al. 2021

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“…To determine the physicochemical properties of a ligand crossing cell membranes in the body, the Lipinski test was carried out. 25 The analysis results with Lipinski's rules of five compounds are demonstrated in Table 3.…”

Section: Resultsmentioning

confidence: 99%

“…Molecular weights over 500 Da cannot diffuse across the cell membrane. 18,25 Perisbivalvin had a molecular weight of 272.26 Da, and mefenamic acid had a molecular weight of 335.87 Da. Perisbivalvin potentially has good penetration power compared to the others.…”

Section: Discussionmentioning

confidence: 99%

Interactions of Perisbivalvin, Apioside, and Pelargonidine 3-Sambubioside Against PTGS2 Receptors

Adrianta

Santoso

Gunawan

et al. 2022

IJPST

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Inflammation is a normal protective response to tissue injury and involves various physiological processes in the body. This study used the prostaglandin synthase 2 (PTGS2) receptor or cyclooxygenase-2 (COX-2) which contributes to prostaglandin synthesis and the regulation of inflammation, and its inhibition is associated with a reduced risk for several colon cancer. Perisbivalvin, apioside, and pelargonidin 3-sambubioside are anthocyanin compounds found in magenta plants. This study aimed to obtain a new candidate as an anti-inflammatory agent targeting the PTGS2 receptor before in vivo testing. Molecular docking in silico with PDB code 5IKR was carried out by optimizing 2 and 3 dimensional chemical structures, conducting method validation, and docking between perisbivalvin compounds and the comparison compound mefenamic acid. The docking results showed that perisbivalvin at -7.63 kcal/mol, apioside at -0.77 kcal/mol, and pelargonidine at -5.74 kcal/mol, while the binding energy of the control compound was at -7.52 kcal/mol through hydrogen bonding interactions with amino acids of TYR385A and SER530A. The prediction results showed the experiment compounds compared to the control compounds were classified as class 4 toxicities. Perisbivalvin compounds are potentially anti-inflammatory because they can bind to the PTGS2 protein.

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“…The Caco-2 monolayer of cells are widely used as an in vitro model of the human intestinal mucosa and have been showing interesting results that predict the absorption of bioactive molecules. Thus, using the pkCSM predictive model, we may consider that a molecule may display a high Caco-2 permeability if it has log P app value higher than 0.90 × 10 −6 cm/s [78]. In that sense, protocatechuic acid is the phenolic compound in onion waste extracts with the highest P app value (1.15 × 10 −6 cm/s), and thus, with the highest Caco-2 permeability.…”

Section: Theoretical Absorption Of Individual Phenolic Compounds (Bas...mentioning

confidence: 99%

Valorization of Onion Waste by Obtaining Extracts Rich in Phenolic Compounds and Feasibility of Its Therapeutic Use on Colon Cancer

et al. 2022

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In this study, the total phenolic content, the antioxidant and antiproliferative activities of onion waste extracts were characterized. Some phenolic compounds present in the extracts were also identified and quantified by HPLC-DAD. Additionally, an in-silico analysis was performed to identify the phenolic compounds with the highest intestinal absorption and Caco-2 permeability. The onion extract possessed a high amount of phenolic compounds (177 ± 9 mg/g extract) and had an effective antioxidant capacity measured by ABTS, FRAP and DPPH assays. Regarding the antiproliferative activity, the onion extracts produced cell cycle arrest in the S phase with p53 activation, intrinsic apoptosis (mitochondrial membrane potential modification) and caspase 3 activation. Likewise, onion waste increased intracellular ROS with possible NF-kB activation causing a proteasome down regulation. In addition, the extracts protected the intestine against oxidative stress induced by H2O2. According to the in-silico analysis, these results could be related to the higher Caco-2 permeability to protocatechuic acid. Therefore, this study provides new insights regarding the potential use of these types of extract as functional ingredients with antioxidant and antiproliferative properties and as medicinal agents in diseases related to oxidative stress, such as cancer. In addition, its valorization would contribute to the circular economy.

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Evaluation of N-benzoylthiourea derivatives as popssible analgesic agents by predicting their hysicochemical and pharmacokinetic properties, toxicity, and analgesic activity

Cited by 12 publications

References 11 publications

Phenolic-Rich Extracts from Avocado Fruit Residues as Functional Food Ingredients with Antioxidant and Antiproliferative Properties

Phenolic-Rich Extracts from Avocado Fruit Residues as Functional Food Ingredients with Antioxidant and Antiproliferative Properties

Interactions of Perisbivalvin, Apioside, and Pelargonidine 3-Sambubioside Against PTGS2 Receptors

Valorization of Onion Waste by Obtaining Extracts Rich in Phenolic Compounds and Feasibility of Its Therapeutic Use on Colon Cancer

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