In Silico Evaluation of Ibuprofen and Two Benzoylpropionic Acid Derivatives with Potential Anti-Inflammatory Activity

Bittencourt, José Adolfo H. M.; Neto, Moysés F. A.; Lacerda, Pedro Sousa; Bittencourt, Renata C. V. S.; Silva, Raí C.; Lobato, Cleison C.; Silva, Luciane B.; Leite, Franco Henrique Andrade; Zuliani, Juliana Pavan; Rosa, Joaquín M C; Borges, Rosivaldo S.; Santos, Cleydson Breno Rodrigues dos

doi:10.3390/molecules24081476

Cited by 28 publications

(25 citation statements)

References 87 publications

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“…The “surviving structures” were submitted to DEREK software [ 40 ] to evaluate toxicological properties, having as reference the properties of the commercial drug Rofecoxib. Thus, only seventy-nine structures were selected because they did not present toxicity alerts and toxicophoric groups [ 21 ]. Subsequently, these structures were subjected to a molecular study to assess binding mode and affinity with h COX-2 receptor.…”

Section: Resultsmentioning

confidence: 99%

“…The three remaining compounds were subjected to the bioactivity prediction, through the Molinspiration server ( ). In this prediction, biological activity measured by the bioactivity score for enzyme inhibitor was evaluated enzyme (see Table 6 ), which are classified into three different ranges: molecule having bioactivity score more than 0.00 is most likely to possess considerable biological activities, while values −0.50 to 0.00 are expected to be moderately active, and if score is less than −0.50, it is presumed to be inactive [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

“…LMQC36 presented a LD 50 value of 6500 mg/kg and classification VI, which is non-toxic if ingested, estimated as the best result of an oral lethal dose. Therefore, the results for LD 50 of the investigated compounds are better than the commercial compound and may present greater safety in use [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

“…The prediction method is based on the analysis of the two-dimensional (2D) similarity to compounds with known LD 50 values and the identification of fragments over-represented in toxic compounds. The results are generated instantly on the server page, showing the predicted average lethal dose (LD 50 ) in mg/kg of weight and the toxicity classes (I, II, III, IV, V and VI) [ 21 , 98 ].…”

Section: Methodsmentioning

confidence: 99%

“…Thus, the similarity and electrostatic potential of the selected structures were performed using computer programs and commercial databases of compounds [ 15 ] and then we performed the filtering of the results considering the pharmacokinetic and toxicological properties [ 16 , 17 , 18 , 19 , 20 ]. Furthermore, the docking simulation evaluated the binding affinity of compounds to COX-2 in comparison with rofecoxib [ 20 , 21 ]. Biological target prediction was used as a screening step through the web server Swiss [ 22 ] and the bioactivity was determined on the Molinspiration web server [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach

et al. 2020

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The cyclooxygenase-2 receptor is a therapeutic target for planning potential drugs with anti-inflammatory activity. The selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was selected as a pivot molecule to perform virtual ligand-based screening from six commercial databases. We performed the search for similarly shaped Rapid Overlay of Chemical Structures (ROCS) and electrostatic (EON) compounds. After, we used pharmacokinetic and toxicological parameters to determine the best potential compounds, obtained through the softwares QikProp and Derek, respectively. Then, the compounds proceeded to the molecular anchorage study, which showed promising results of binding affinity with the hCOX-2 receptor: LMQC72 (∆G = −11.0 kcal/mol), LMQC36 (∆G = −10.6 kcal/mol), and LMQC50 (∆G = −10.2 kcal/mol). LMQC72 and LMQC36 showed higher binding affinity compared to rofecoxib (∆G = −10.4 kcal/mol). Finally, molecular dynamics (MD) simulations were used to evaluate the interaction of the compounds with the target hCOX-2 during 150 ns. In all MD simulation trajectories, the ligands remained interacting with the protein until the end of the simulation. The compounds were also complexing with hCOX-2 favorably. The compounds obtained the following affinity energy values: rofecoxib: ΔGbind = −45.31 kcal/mol; LMQC72: ΔGbind = −38.58 kcal/mol; LMQC36: ΔGbind = −36.10 kcal/mol; and LMQC50: ΔGbind = −39.40 kcal/mol. The selected LMQC72, LMQC50, and LMQC36 structures showed satisfactory pharmacokinetic results related to absorption and distribution. The toxicological predictions of these compounds did not display alerts for possible toxic groups and lower risk of cardiotoxicity compared to rofecoxib. Therefore, future in vitro and in vivo studies are needed to confirm the anti-inflammatory potential of the compounds selected here with bioinformatics approaches based on rofecoxib ligand.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach

et al. 2020

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Exploring ibuprofen derivatives as α‐glucosidase and lipoxygenase inhibitors: Cytotoxicity and in silico studies

Daud

Abid

Sardar

et al. 2022

Archiv der Pharmazie

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This study reports the synthesis of a series of ibuprofen derivatives, including thiosemicarbazides 4a-f, 1,3,4-oxadiazoles 5a-f, 1,3,4-thiadiazoles 6a-f, 1,2,4triazoles 7a-f, and their S-alkylated derivatives 8a-d. All of the newly synthesized derivatives were analyzed using 1 H NMR, 13 C NMR spectroscopy, and highresolution mass spectra (electron ionization) spectrometry. These synthetic molecules were examined for their in vitro baking yeast α-glucosidase and soybean 15-lipoxygenase (15-LOX) inhibition and cell viability studies. The results revealed that the compounds N-(3,4-dichlorophenyl)−5-[1-(4-isobutylphenyl)ethyl]-1,3,4oxadiazol-2-amine 5f (IC 50 3.05 ± 1.23 µM) and N-(3-fluorophenyl)-5-[1-(4isobutylphenyl)ethyl]-1,3,4-oxadiazol-2-amine 5b (IC 50 3.12 ± 1.21 µM) were the most potent with respect to the α-glucosidase enzyme while in case of 15-LOX, the compound 4-(2,4-dichlorophenyl)-1-[2-(4-isobutylphenyl)propanoyl]thiosemicarbazide 4e showed potent inhibition with an IC 50 value of 55.41 ± 0.41 µM. All these compounds were found least toxic by displaying a blood mononuclear cell viability value of 69.2%-97.8% by the MTT assay compared to the standards when assayed at 0.25 mM concentration. Molecular docking analyses were conducted to evaluate the inhibition profiles of these derivatives against the said enzymes and the data supported the in vitro profiles.

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Identification of Bioactive Compounds against Aedes aegypti (Diptera: Culicidae) by Bioassays and in Silico Assays

Brito

Oliveira

Silva

et al. 2021

Chemistry & Biodiversity

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Most of the hematophagous insects act as disease vectors, including Aedes aegypti, responsible for transmitting some of the most critical arboviruses globally, such as Dengue. The use of repellents based on natural products is a promising alternative for personal protection compared to industrial chemical repellents. In this study, the repellent effect of essential oils extracted from Lippia thymoides, Lippia alba, Cymbopogon winterianus, and Eucalyptus globulus leaves was evaluated. Essential oils used showed repellent activity against Ae. aegypti in laboratory bioassays, obtaining protection rates above 70 % from 3.75 mg/mL and higher concentration for all analyzed oils. GC/MS identified 57 constituents, which were used in the ligand‐based pharmacophore model to expose compounds with requirements for repellents that modulate mosquitoes behavior through odorant‐binding protein 1 Ae. aegypti. Ligand‐based pharmacophore model approach results suggested that repellent activity from C. winterianus, L. alba, and L. thymoides essential oils’ metabolites is related to Citronelal (QFIT=26.77), Citronelol (QFIT=11.29), Citronelol acetate (QFIT=52.22) and Geranil acetate (QFIT=10.28) with synergistic or individual activity. E. globulus essential oil's repellent activity is associated with Ledol (0.94 %; QFIT=41.95). Molecular docking was applied to understand the binding mode and affinity of the essential oils’ data set at the protein binding site. According to molecular docking, Citronelol (ChemPLP=60.98) and geranyl acetate (ChemPLP=60.55) were the best‐classified compounds compared to the others and they can be explored to develop new repellents.

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In Silico Evaluation of Ibuprofen and Two Benzoylpropionic Acid Derivatives with Potential Anti-Inflammatory Activity

Cited by 28 publications

References 87 publications

Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach

Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach

Exploring ibuprofen derivatives as α‐glucosidase and lipoxygenase inhibitors: Cytotoxicity and in silico studies

Identification of Bioactive Compounds against Aedes aegypti (Diptera: Culicidae) by Bioassays and in Silico Assays

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