In Silico Analysis and Experimental Evaluation of Ester Prodrugs of Ketoprofen for Oral Delivery: With a View to Reduce Toxicity

Mazumder, Kishor; Hossain, Md. Emran; Aktar, Asma; Mohiuddin, Mohammad; Sarkar, Kishore Kumar; Biswas, Biswajit; Aziz, Md. Abdullah; Abid, Md. Ahsan; Fukase, Koichi

doi:10.3390/pr9122221

Cited by 11 publications

(6 citation statements)

References 59 publications

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“…1). This observed effect was in concordance with the communicated literature data, regarding the effects of this analgesic-antipyretic drug in this experimental somatic pain model in rodents [31,32].…”

Section: Resultssupporting

confidence: 92%

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The Analgezic Effect of Vortioxetine on somatic and visceral Pain using the mouse models

2022

pnr

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Experimental investigation of the vortioxetine effects on somatic and visceral nociception in mice. Material and method: We used healthy, non-genetically modified white Swiss mice (20-25 g), randomly assigned in 3 groups of 6 animals each, treated orally 14 consecutive days, as follows: Group I (DW): distilled water 0,1 ml/10 g body weight, Group 2 (VRT): 20 mg/kbw vortioxetine. In the 14 th day of the experiment the Group 3 (KET) received the positive control drug ketoprofen (15 mg/kbw), 15 minutes before the performing the tests. The somatic pain testing was performed using hot plate assay. The writhing test based on chemical peritoneal irritation induced by diluted acetic acid (0,6%) was used as standardized visceral pain model. The data were statistically analyzed using SPSS variant 17.0 for Windows and ANOVA one-way method. The research protocol was approved by the Grigore T. Popa University`s Committee for Research and Ethical Issues. Results: Ketoprofen showed a substantial and progressive prolongation in reaction time in hot plate test, respectively a decrease in the behavioral manifestations in writhing test. The administration of vortioxetine resulted in a considerable increase in the time response to thermal noxious paws stimulation in hot plate test, and a diminution in the number of writhes in writhing test. Conclusion:Using the mouse models of acute pain hot plate analgesia meter and acid acetic writhing test, we revealed that the oral administration of vortioxetine during 14 days resulted in significant somatic and visceral analgesic effects, but less intense than of ketoprofen.

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Section: Resultssupporting

confidence: 92%

“…3). The results are congruent with the data existent in the literature, regarding the effects of this analgesic-antipyretic drug writhing test in rodents [31,33,34].…”

Section: Resultssupporting

confidence: 91%

The Analgezic Effect of Vortioxetine on somatic and visceral Pain using the mouse models

2022

pnr

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“…The toxicological properties of compounds were investigated using OSIRIS Property Explorer Software (Available online: ) [ 43 ] and the ProToxII free web tool [ 44 , 45 ]. Both programs assess the mutagenic, tumorigenic, irritant, and reproductive risks of a compound administered as a medicinal product.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Molecular Docking, and Biological Evaluation of Novel Anthranilic Acid Hybrid and Its Diamides as Antispasmodics

Milusheva,

Gledacheva,

Stefanova

et al. 2023

IJMS

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The present article focuses on the synthesis and biological evaluation of a novel anthranilic acid hybrid and its diamides as antispasmodics. Methods: Due to the predicted in silico methods spasmolytic activity, we synthesized a hybrid molecule of anthranilic acid and 2-(3-chlorophenyl)ethylamine. The obtained hybrid was then applied in acylation with different acyl chlorides. Using in silico analysis, pharmacodynamic profiles of the compounds were predicted. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial, cytotoxic, anti-inflammatory activity, and ex vivo spasmolytic activity. Density functional theory (DFT) calculation, including geometry optimization, molecular electrostatic potential (MEP) surface, and HOMO-LUMO analysis for the synthesized compounds was conducted using the B3LYP/6–311G(d,p) method to explore the electronic behavior, reactive regions, and stability and chemical reactivity of the compounds. Furthermore, molecular docking simulation along with viscosity measurement indicated that the newly synthesized compounds interact with DNA via groove binding mode. The obtained results from all the experiments demonstrate that the hybrid molecule and its diamides inherit spasmolytic, antimicrobial, and anti-inflammatory capabilities, making them excellent candidates for future medications.

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“…SwissADME was used to screen the compounds based on Lipinski’s violations (above 1 violation compounds excluded), PAINS alerts (0 alert compounds), Bioavailability score (0.55 minimum) and synthetic accessibility (1 to 7). Every drug molecule should obey the Lipinski rule and Bioavailability score [ 38 ]. Here, 303 compounds were obeyed out of 1,207 compounds ( S2 File ).…”

Section: Resultsmentioning

confidence: 99%

Interleukin-10 as Covid-19 biomarker targeting KSK and its analogues: Integrated network pharmacology

et al. 2023

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COVID-19 caused by the SARS-CoV-2 virus is widespread in all regions, and it disturbs host immune system functioning leading to extreme inflammatory reaction and hyperactivation of the immune response. Kabasura Kudineer (KSK) is preventive medicine against viral infections and a potent immune booster for inflammation-related diseases. We hypothesize that KSK and KSK similar plant compounds, might prevent or control the COVID-19 infection in the human body. 1,207 KSK and KSK similar compounds were listed and screened via the Swiss ADME tool and PAINS Remover; 303 compounds were filtered including active and similar drug compounds. The targets were retrieved from similar drugs of the active compounds of KSK. Finally, 573 genes were listed after several screening steps. Next, network analysis was performed to finalize the potential target gene: construction of protein-protein interaction of 573 genes using STRING, identifying top hub genes in Cytoscape plug-ins (MCODE and cytoHubba). These ten hub genes play a crucial role in the inflammatory response. Target-miRNA interaction was also constructed using the miRNet tool to interpret miRNAs of the target genes and their functions. Functional annotation was done via DAVID to gain a complete insight into the mechanism of the enriched pathways and other diseases related to the given target genes. In Molecular Docking analysis, IL10 attained top rank in Target-miRNA interaction and also the gene formed prominent exchanges with an excellent binding score (> = -8.0) against 19 compounds. Among them, Guggulsterone has an acute affinity score of -8.8 for IL10 and exhibits anti-inflammatory and immunomodulatory properties. Molecular Dynamics simulation study also performed for IL10 and the interacting ligand compounds using GROMACS. Finally, Guggulsterone will be recommended to enhance immunity against several inflammatory diseases, including COVID19.

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In Silico Analysis and Experimental Evaluation of Ester Prodrugs of Ketoprofen for Oral Delivery: With a View to Reduce Toxicity

Cited by 11 publications

References 59 publications

The Analgezic Effect of Vortioxetine on somatic and visceral Pain using the mouse models

The Analgezic Effect of Vortioxetine on somatic and visceral Pain using the mouse models

Synthesis, Molecular Docking, and Biological Evaluation of Novel Anthranilic Acid Hybrid and Its Diamides as Antispasmodics

Interleukin-10 as Covid-19 biomarker targeting KSK and its analogues: Integrated network pharmacology

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