Standard Ibuprofen Research Articles

Ultrasonic synthesis, characterization, DFT and molecular docking of a biocompatible Zn-based MOF as a potential antimicrobial, anti-inflammatory and antitumor agent

Zinc metal–organic frameworks have emerged as promising candidates, demonstrating excellent biological properties stemming from the unique characteristics of MOFs and zinc. In this study, we employed a facile method to synthesize a zinc metal–organic framework [Zn(IP)(H2O)] using ultrasound irradiation, with the linker being isophthalic acid (IPA) (1,3-benzene dicarboxylic acid). The parent Zn-MOF and two Ag/Zn-MOF samples prepared via loading and encapsulation methods were comprehensively characterized using various techniques, including FT-IR, XRD, SEM, TEM, N2 adsorption–desorption isotherm, UV–vis spectroscopy and TGA. The parent Zn-MOF and two Ag/Zn-MOF samples exhibited a broad spectrum of antibacterial effects. Remarkably, genomic DNA of P. aeruginosa was effectively degraded by Zn-MOF, further supporting its potent antibacterial results. The free radical inhibition assay demonstrated a 71.0% inhibition under the influence of Zn-MOF. In vitro cytotoxicity activity of Zn-MOF against HepG-2 and Caco-2 cell lines revealed differential cytotoxic effects, with higher cytotoxicity against Caco-2 as explored from the IC50 values. This cytotoxicity was supported by the high binding affinity of Zn-MOF to CT-DNA. Importantly, the non-toxic property of Zn-MOF was confirmed through its lack of cytotoxic effects against normal lung cell (Wi-38). The anti-inflammatory treatment of Zn-MOF achieved 75.0% efficiency relative to the standard Ibuprofen drug. DFT and docking provided insights into the geometric stability of Zn-MOF and its interaction with active amino acids within selected proteins associated with the investigated diseases. Finally, the synthesized Zn-MOF shows promise for applications in cancer treatment, chemoprevention, and particularly antibacterial purposes.

Synthesis and anti-inflammatory activity of benzimidazole derivatives; an in vitro, in vivo and in silico approach

Many non-steroidal anti-inflammatory drugs (NSAIDs) concurrently inhibit both COX-1 and COX-2, with a preference for specifically targeting COX-2 due to its significant involvement in various pathologies. In addition to COX enzymes, several other targets, including Aldose reductase, Aldo-ketoreductase family 1-member C2, and Phospholipase A2, have been identified as contributors to inflammation and a myriad of other diseases.In this context, a series of 2-substituted benzimidazole derivatives was synthesized and assessed for their anti-inflammatory potential through both in vitro and in vivo assays. Molecular docking studies were conducted to elucidate the mechanism of action of these compounds against COX enzymes and other therapeutic targets associated with NSAIDs, such as Aldose reductase, AIKRC, and Phospholipase A2.Among the synthesized compounds, B2, B4, B7, and B8 demonstrated IC50 values lower than the standard ibuprofen, as determined by the Luminol-enhanced chemiluminescence assay. Validation of these findings was achieved through an in vivo carrageenan-induced mice paw edema model, confirming a comparable anti-inflammatory effect to diclofenac sodium observed in vitro. Notably, these compounds exhibited significant binding affinity with all therapeutic targets investigated in this study.These results suggest that the newly synthesized derivatives possess noteworthy anti-inflammatory potential, warranting further exploration for the development of novel multi-targeting inhibitors.

Novel Schiff base derivatives containing 4,5-disubstituted thiazole as potential antibiofilm, anti-inflammatory and antioxidant agents: Green synthesis, molecular docking and ADME analysis

We report the microwave-assisted (MW) green synthesis of some novel 4,5 disubstituted thiazole-containing Schiff base derivatives (SBs) as antibiofilm, anti-inflammatory, and antioxidant agents. Spectroscopic techniques were used to confirm the formation of synthesized compounds. In-vitro antibiofilm and antifungal activity of synthesized molecules were evaluated against the Candida albicans strain (MTCC 227) by broth dilution method. Among the tested molecules, 3a showed excellent inhibition of both biofilm formation and planktonic growth at much lower MIC50 values (5.56 μg/mL and 1.20 μg/mL respectively) than other derivatives. Moreover, the spot assay of compound 3a showed fungicidal activity (100% cell death) for biofilm formation and planktonic growth at the lowest MFC values (10 μg/mL and 3.12 μg/mL respectively) compared to the standard drug fluconazole. In addition, the biofilm inhibition was further confirmed by morphological study through FESEM analysis. The anti-inflammatory study of SBs by protein denaturation method indicates that compound 3a (63.19%) was the most active anti-inflammatory agent at a lower concentration of 100 μg/mL in the series than the standard ibuprofen (42.36%). Whereas, the antioxidant study of SBs by the DPPH scavenging method shows compound 3j (IC50 = 436.10 μg/mL) was the more potent antioxidant agent as compared to other tested compounds and standard drug ascorbic acid (IC50 = 626.99 μg/mL). Furthermore, the molecular docking study of SBs with the active sites of sterol 14-α demethylase CYP51 enzyme of (PDB:5TZ1) C. albicans shows strong binding properties, supporting the experimental results of inhibition of biofilm formation. Additionally, the ADME characteristic of SBs demonstrates their potential for development as oral medication candidates.

Insilico Assessment of Phytoconstituents in Myxopyrum Smilacifolium Blume against Arthritis

Myxopyrum smilacifolium Blume geographical occurrence is southern part of India and its usage for the treatment of various diseases has been marked in Traditional Medicine. The present study was aimed to examine the phytoconstituents in Myxopyrum smilacifolium Blume for antiarthritic activity by insilico approach. Antiarthritic activity of phytoconstituents in Myxopyrum smilacifolium Blume was performed by using software Autodock 4.0. For each phytoconstituents the pharmacokinetic parameters are also assessed by online tools. The study revealed that phytocompounds, Arenarioside, Verbascoside and Myxopyroside showed docking score of about -16.4 kcal/mol, -10.6kcal/mol and -6.5 kcal/mol comparatively high when compared with the docking score of standard Ibuprofen of about -6.2 kcal/mol. It had proven to posses the inhibition activity against inflammatory mediator as it shown a good binding affinity between ligand and the receptor site COX-2. The evaluated pharmacokinetic parameters of the only 3 phytoconstituents obeyed Lipinski’s rule of 5. Arenarioside, Verbascoside and Myxopyroside are the phytoconstituents of Myxopyrum smilacifolium Blume shown high docking score and it can be explored further for SAR and simulation studies are needed to ensure the antiarthritic activity.

Unleashing the potential of vanillic acid: A new twist on nature's recipe to fight inflammation and circumvent azole-resistant fungal infections

Vanillic acid (VA) — a naturally occurring phenolic compound in plants — is not only used as a flavoring agent but also a prominent metabolite post tea consumption. VA and its associated compounds are believed to play a significant role in preventing diseases, underscoring the need for a systematic investigation. Herein, we report a 4-step synthesis employing the classical organic reactions, such as Willamson’s alkylation, Fischer-Spier reaction, and Steglich esterification, complemented with a protection-deprotection strategy to prepare 46 VA derivatives across the five series (1a–1i, 2a–2i, 3, 3a–3i, 4a–4i, 5a–5i) in high yields. The synthesized compounds were investigated for their antifungal, anti-inflammatory, and toxic effects. Notably, compound 1a demonstrated remarkable ROS inhibition with an IC50 value of 5.1 ± 0.7 µg/mL, which is more than twice as effective as the standard ibuprofen drug. A subset of the synthesized derivatives (2b, 2c, 2e, 3b–3d, 4a–4c, 5a, and 5e) manifested their antifungal effect against drug-resistant Candida strains. Compound 5g, in particular, revealed synergism with the established antifungal drugs amphotericin B (AMB) and fluconazole (FLZ), doubling FLZ's potency against azole resistant Candida albican ATCC 36082. Furthermore, 5g improved the potency of these antifungals against FLZ-sensitive strains, including C. glabrata ATCC 2001 and C. parapsilosis ATCC 22019, as well as various multidrug-resistant (MDR) Candida strains, namely C. albicans ATCC 14053, C. albicans CL1, and C. krusei SH2L OM341600. Additionally, pharmacodynamics of compound 5g was examined using time-kill assay, and a benign safety profile was observed with no hemolytic activity in whole blood, and no cytotoxicity towards the normal BJ human cell line. The synergistic potential of 5g was further investigated through both experimental methods and docking simulations.These findings highlight the therapeutic potential of VA derivatives, particularly in addressing inflammation and circumventing FLZ resistance in Candida albicans.

Bio-pesticidal, Antimicrobial, and Anti-inflammatory Potentials of n-Hexane Fraction of Zanthoxylum armatum DC and its Chemical Profiling

Zanthoxylum armatum DC, commonly known as toothache tree, is utilized for treating inflamed gums. The plant’s volatile constituent possesses a robust fragrance and contributes to its tangy taste. This study investigates the bioactivities, including bio-pesticidal, antimicrobial, and anti-inflammatory properties as well as the chemical profiling of the n-hexane fraction based on GC-MS analysis. The evaluated activities involve contact toxicity, microplate alamar blue assay, against three different insects, five bacteria, and seven fungi, and oxidative burst assay. The NIST library serves as a standard reference database for constituent identification. Remarkable insecticidal activities comparable to the standard drug permethrin were observed, particularly against Rhyzopertha dominica (100%), Tribolium castaneum (60%), and Sitophilus oryzae (50%). The fraction exhibited significant antifungal activity against Fusarium lini (85%) and notable inhibition against B. subtillis (67.27%) and S. aureus (65.25%). Potent anti-inflammatory effects were noted with an IC50 value of 11.2±1.9 μg/ml, equivalent to standard ibuprofen at various concentrations. GC-MS analysis identified twenty compounds, with major ones including trans-13-octadecenoic acid (36.08%), cis-9 hexadecenoic acid (18.66%), and 2-propenoic acid 3 phenyl methyl ester (11.08%). The diverse bioactivities observed may be attributed to the varied nature of compounds such as polyunsaturated fatty acids and their oxides. This research revealed the potential of Z. armatum as a potential bio-pesticide, anti-inflammatory, and antimicrobial agent.

Nauclea latifolia Stem Bark Extracts: Potentially Effective Source of Antibacterial, Antioxidant, Antidiabetic and Anti-Inflammatory Compounds

The stem bark of African peach (Nauclea latifolia) plant is used as traditional remedy for diabetes and inflammatory diseases, however, authenticated information on this use is scare. Therefore, the objective of this paper was to investigate the traditional folklore of the trado-medical remedy of the stem bark of African peach (Nauclea latifolia) plant for diabetes and inflammatory diseases using appropriate standard methods. Qualitative phytochemical screening confirmed the presence of saponins, alkaloids alkaloids, flavonoids, tannins, coumarin, steroids, terpenoids, cardiac glycosides, glycosides, quinones, anthocyanin, anthraquinone, and phenol in the extracts. The ethanol extract exhibited the highest quantities of phenolics (19.69±0.12 mgGAE/g), flavonoids (46.84±0.12 mgQE/g), alkaloids (8.76±0.10 mg/g), tannins (7.25±0.10 mgTAE/g), and saponins (4.53±0.13 mg/g). Both ethyl acetate and ethanol extracts showed potent antibacterial and significant antifungal potential against the chosen pathogenic species. The ethyl acetate extract showed superior antioxidant and anti-diabetic activities compared to the ethanol extract. However, the ethanol extract outperformed in terms of anti-inflammatory efficacy, although still below standard Ibuprofen. This study propounds that N. latifolia stem bark is an attainable diabetic medication due to its interactions with enzymes, antioxidants, and anti-inflammatory capabilities and its potential for isolating medicinal compounds.

Anticancer and anti-inflammatory activity and untargeted metabolite profiling by UPLC-ESI-QTOF of crude extracts of mangrove endophytic fungus Aspergillus stellatus LM-03

Mangrove ecosystem is diverse habitat for number of medicinally important microorganisms including fungi. Scientific research from last three decade emphasises it potential in important secondary metabolites production, which have wide biological activities. The current study elaborates isolation of fungi from pneumatophore of mangrove plant Avicennia marina and investigation of ethyl acetate extract for antimicrobial, anti-inflammatory and anticancer activity. Ethyl acetate extract of the fungus displayed maximum anti-inflammatory activity with 76.39% inhibition for by protein denaturation method and 22.52% inhibition for membrane stabilisation method with respect to standard ibuprofen. Further, the anticancer activity of Aspergillus stellatus LM-03 exhibited against MCF-7 of breast cancer cell with an IC50 value of 33.24 µg/ml. HPLC and UPLC-ESI-QTOF analysis displayed nine compound mainly alternariol monomethyl ether and methyl jasmonate, which are highly anticancer activity and moderate anti-inflammatory activity with other compounds as angelic anhydride, DL-3-(4-Hydroxyphenyl)lactic acid, 8,9-epoxyl-3-isobutyryloxy-10-(2-methylbutanoyl)thymol, 5-(6-methyl-7-oxooctyl) furan-2(5H)-one and phenyl-butyryl-glutamine with an unidentified compounds. The results of the current study indicate that it may be worthwhile to investigate Aspergillus stellatus LM-03 extract for promising bioactive metabolites with potential for medicinal use.

Screening of potent inhibitor from Aquilaria malaccensis Lam. against arachidonic inflammatory enzymes: an insight from molecular docking, ADMET, molecular dynamics simulation and MM-PBSA approaches

The three primary enzymes COX (cyclooxygenase), LOX (lipoxygenase) and CYT-P450 (cytochrome P450), which are part of the arachidonic inflammatory pathway, play crucial role in the development of asthma, rheumatoid arthritis and cardiovascular diseases. Ethnomedicinally, plant-derived chemicals have a major role in the treatment of fatal illnesses. Aquilaria malaccensis Lam. widely known as agarwood is prized for its fragrance and therapeutic properties. The phytochemicals and extracts of this plant have significant healing properties in the treatment of serious illnesses. In the current work, an in-silico approach including molecular docking, ADMET (absorption, distribution, metabolism, excretion and toxicity), molecular dynamics (MD) simulation and molecular mechanics/Poisson–Boltzmann surface area (MM-PBSA) was performed to screen 33 bioactive compounds from this plant against COX-2 and 5-LOX in order to find the most effective inhibitor. 2-(2-Phenylethyl)chromone was found to inhibit both 5-LOX and COX-2, showing the highest binding affinities (−9.1 kcal/mol and −9.0 kcal/mol, respectively) than standard Ibuprofen and nordihydroguaiaretic acid (NDGA). 2-(2-Phenylethyl)chromone showed the highest drug-likeness score and low risk of toxicity compared to other phytochemicals. MD modeling and MM-PBSA calculations showed that 2-(2-Phenylethyl)chromone had a strong persistent binding interaction with 5-LOX than COX-2, and this interaction is comparable to the bounded standards Ibuprofen and NDGA. From this study, we may infer that the 2-(2-Phenylethyl)chromone can serve as a potent inhibitor and has scope to be employed in the treatment of inflammatory ailments. Communicated by Ramaswamy H. Sarma

Potent ROS inhibitors from Zanthoxylum armatumDC of Nepali origin

A bioassay-guided isolation on the plant Zanthoxylum armatum DC yielded compounds tambulin (1), and prudomestin (2), from ethyl acetate fraction which showed the highest ROS inhibiting activity (IC50 = 17.8 ± 1.1 µg/mL). Structure elucidation of pure compounds was done using mass and NMR spectroscopic techniques. Compounds 1 and 2 revealed potent ROS inhibition with IC50 = 7.5 ± 0.3 and 1.5 ± 0.3 µg/mL, respectively, as compared to standard ibuprofen (IC50 = 11.2 ± 1.9 µg/mL). Likewise, both compounds 1 and 2 showed potent antioxidant activity with IC50 = 32.65 ± 0.31 and 26.96 ± 0.19 µg/mL, respectively. In vitro studies were supported by molecular docking and drug-likeliness properties. In silico studies of 1 and 2 with cyclooxygenase-2 (COX-2) showed perfect binding affinity with binding energies of −8.4 and −8.6 kcal/mol, respectively, comparable to standard ibuprofen (−7.7 kcal/mol). Drug likeness and ADMET showed higher gastrointestinal absorption of 1 and 2 and no toxic impact.

HPLC Analysis and In Vitro and In Silico Evaluation of the Biological Activity of Polyphenolic Components Separated with Solvents of Various Polarities from Helichrysum italicum.

Helichrysum italicum has piqued the interest of many researchers in recent years, mostly for its essential oil, but increasingly for its polyphenolic content as well. In the current study, we examine the polyphenolic composition of H. italicum grown in Bulgaria. The polyphenolic complex was fractionated with solvents of various polarities, including hexane, chloroform, ethyl acetate, and butanol, in order to assess the biological impact of the components. HPLC-PDA and UHPLC-MS/MS were used to examine all fractions. The green coffee fingerprint profile was employed as a "surrogate standard" in the polyphenolic components detection approach. From the UHPLC-MS/MS analysis, we identified 60 components of the polyphenolic complex such as quercetin 3-O-glucuronide, quercetin acetyl-glycoside, isorhamnetin acetyl-glycoside, isorhamnetin caffeoyl-glycoside, quercetin caffeoyl-malonyl-glycoside, isorhamnetin coumaroyl-glycoside, coumaroyl-caffeoylquinic acid, and diCQA-acetyl-derivative were first reported in the composition of H. italicum. The biological activity of the fractions was evaluated in vitro and in silico, which included the fight against oxidative stress (hydrogen peroxide scavenging activity (HPSA), hydroxyl radical scavenging activity (HRSA), metal-chelating activity (MChA)) and nitrosative (nitric oxide scavenging activity) (NOSA)), in vitro anti-inflammatory, and anti-arthritic activity. Results are presented as IC50 ± SD μg/mL. The analysis showed that the EtOAc fraction was characterized by highest HPSA (57.12 ± 1.14 μg/mL), HRSA (92.23 ± 1.10 μg/mL), MChA (5.60 ± 0.17 μg/mL), and NOSA (89.81 ± 2.09 μg/mL), while the hexane and chloroform fractions showed significantly higher in vitro anti-inflammatory activity (30.48 ± 2.33 μg/mL, 62.50 ± 1.69 μg/mL) compared to the standard ibuprofen. All three fractions showed potential anti-arthritic activity (102.93 ± 8.62 μg/mL, 108.92 ± 4.42 μg/mL, 84.19 ± 3.89 μg/mL).

Synthesis, Computational Studies, Antioxidant and Anti-Inflammatory Bio-Evaluation of 2,5-Disubstituted-1,3,4-Oxadiazole Derivatives.

The 1,3,4-oxadiazole derivatives Ox-6a-f have been synthesized by incorporating flurbiprofen moiety with the aim to explore the potential of target molecules to decrease the oxidative stress. The title compounds Ox-6a-f were prepared by simple reactions in which a flurbiprofen -COOH group was esterified with methanol in an acid-catalyzed medium, which was then reacted with hydrazine to afford the corresponding hydrazide. The acid hydrazide was then cyclized into 1,3,4-oxadiazole-2-thiol by reacting with CS2 in the presence of KOH. The title compounds Ox-6a-f were synthesized by the reaction of an -SH group with various alkyl/aryl chlorides, which involves an S-alkylation reaction. The structures of the synthesized Ox-6a-f derivatives were ascertained by spectroscopic data. The in silico molecular docking was performed against target proteins cyclooxygenase-2 COX-2 (PDBID 5KIR) and cyclooxygenase-1 COX-1 (PDBID 6Y3C) to determine the binding affinity of the synthesized compounds with these structures. It has been inferred that most of the synthesized compounds bind well with an active binding site of 5KIR compared to 6Y3C, and especially compound Ox-6f showed excellent binding affinity (7.70 kcal/mol) among all synthesized compounds Ox-6a-f. The molecular dynamic (MD) simulation has also been performed to check the stability of docking complexes of ligands with COX-2 by determining their root mean square deviation and root mean square fluctuation. Little fluctuation was observed in case of Ox-6f, which forms the most stable complex with COX-2. The comprehensive antioxidant potential of the synthesized compounds has been evaluated by determining their free radical scavenging activity, including DPPH, OH, nitric oxide (NO), and iron chelation assay. The derivative Ox-6f showed promising results with 80.23% radical scavenging potential at a dose of 100 µg/mL while ascorbic acid exhibited 87.72% inhibition at the same dose. The anti-inflammatory activity of the final products has also been performed, and inflammatory markers were assayed, such as a thiobarbituric acid-reducing substance, nitric oxide, interleukin-6 (IL-6), and COX-2. The derivatives Ox-6d and Ox-6f displayed higher anti-inflammatory activity, exhibiting 70.56% and 74.16% activity, respectively. The results were compared with standard ibuprofen, which showed 84.31% activity at the same dose, 200 µg/mL. The anti-inflammatory potential has been performed by following the carrageen-induced hind paw edema model, and results showed that derivative Ox-6f exhibited 79.83% reduction in edema volume compared to standard ibuprofen, which reduced 84.31% edema volume. As dry lab and wet lab results confirm each other, it has been deduced that derivative Ox-6f may serve as the lead structure to design potent compounds to address oxidative stress.

Exploring the Antioxidant and Anti-Inflammatory Potential of Wilckia maritima: In Vitro and In Silico Investigations

This research aimed to assess the anti-inflammatory and antioxidant potential of methanol extract of Wilckia maritima, a plant belonging to the family Brassicaceae, which is enriched with natural antioxidants. Qualitative phytochemical studies showed the presence of numerous compounds including glycosides, phenols, triterpenoids, and GC-MS studies revealed the presence of 35 bioactive components, including n-hexadecanoic acid (26.96%), 9,12,15 octadecatrienoic acid (cis) (25.52%), 3,5 di-hydroxy-6-methyl 2,3-di-hydro-4-pyran 4-one (14.35%), and 3-tertiary butyl-4-hydroxy-anisol (11.68%) as major components, which are thought to be responsible for anti-inflammatory and antioxidant potentials of methanol extract of W. maritima., flavonoids, steroids, tannins, and saponins. The antioxidant potential of the extract was determined by performing various assays, including DPPH free radical scavenging, ferrous reducing, and hydrogen peroxide assays, which showed significant percentage inhibition (83.55 ± 0.89, 79.40 ± 1.17, and 81.26 ± 0.36%, respectively) as compared to ascorbic acid (standard). The extract also exhibited significant anti-inflammatory activity with percentage inhibition 65.66 ± 0.42% compared to standard ibuprofen, which showed 73.20 ± 0.21% inhibition. In vivo analysis further confirmed this anti-inflammatory potential of the extract, showing a 75.55 ± 0.11% reduction in edema at 300 mg/kg as compared with standard diclofenac sodium 70.27 ± 0.012%. Moreover, in silico investigations revealed that the phytocompounds in W. maritima exhibited excellent antioxidant and anti-inflammatory characteristics, which could provide novel biological molecules for target receptors. Overall, our findings suggest that W. maritima can be utilized as a potential resource of natural compounds with antioxidants and anti-inflammatory potential, with promising therapeutic effect in relieving various ailments related to inflammatory response.

Synthesis, in silico studies and biological screening of (E)-2-(3-(substitutedstyryl)-5-(substitutedphenyl)-4,5-dihydropyrazol-1-yl)benzo[d]thiazole derivatives as an anti-oxidant, anti-inflammatory and antimicrobial agents

A new series of (E)-2-(3-(substitutedstyryl)-5-(substitutedphenyl)-4,5-dihydropyrazol-1-yl)benzo[d]thiazole derivatives was synthesized and the chemical structures of synthesized compounds were deduced by IR and NMR spectral tools. These compounds were synthesized via aldol condensation reaction of substituted benzaldehydes and acetone in alkaline ethanolic solution and their in vitro anti-oxidant, anti-inflammatory and antimicrobial activities were investigated. All the synthesized compounds displayed anti-oxidant potential with IC50 values ranging from 0.13 to 8.43 µmol/ml. The compound Z13 exhibited potent anti-inflammatory activity with IC50 value of 0.03 µmol/ml compared with the standard ibuprofen, which showed IC50 value of 0.11 µmol/ml. On the other hand, most of the compounds had a certain antibacterial potential particularly against P. aeruginosa and among these derivatives, compound Z2 exhibited the highest potential against P. aeruginosa with MIC value of 0.0069 µmol/ml. The analysis of docking results demonstrated the binding affinity and hydrogen bond, electrostatic and hydrophobic interactions of all the synthesized compounds with their respective targets. In silico ADMET studies were carried out for the synthesized compounds and most of the compounds exhibited good ADMET profile.

FASTER ABSORPTION OF IBUPROFEN LYSINATE THAN STANDARD IBUPROFEN ACID IN PEDIATRIC POST-SURGICAL PAIN

FASTER ABSORPTION OF IBUPROFEN LYSINATE THAN STANDARD IBUPROFEN ACID IN PEDIATRIC POST-SURGICAL PAIN

Synthesis, characterization, computational, anticancer and anti-inflammatory studies of pregabalin esters and their complexes with heavy metals

The current study entails a series of pregabalin ester complexed with zinc and copper; further characterized by spectroscopic techniques and biological assays. Docking analysis revealed three complexes with favorable binding interactions which were further subjected to in-vitro anti-inflammatory and anticancer activities. The complex-5 displayed most potent anti-inflammatory activity against Luminol-enhanced Chemiluminescence assay with IC50 value of 7.7 ± 0.8 µM as compared to standard Ibuprofen with IC50 value of 11.2 ± 1.9 µM; whereas none of them showed significant outcomes against HeLa cell lines for antiproliferative activity as compared with standard doxorubicin. Computational studies were carried out using the reported crystal structure of multidrug resistant Alpha2S protein (PDB-ID: 6ND9), neurokinin-1 receptor (PDB-ID: 2KSA) and dihydrofolate reductase (PDB-ID: 3GHW); indicating the compound 3 showed significant interactions at all receptors. As the analogues were more active than parent drug in some respects; therefore, the expansion of the project can be planned to carry out more pharmacological screening.

Marine cuttlefish derived 2H-benzochromenone: Pharachromenone as a dual inhibitor of pro-inflammatory 5-lipoxygenase and cyclooxygenase-2.

Cephalopod cuttlefish, Sepia pharaonis, has been considered as a commercially important resource, which is widely regarded as nutritious food in the southwest of Indian and Mediterranean coasts. Chemical analysis of the crude extract of S. pharaonis resulted in the isolation of an undescribed 2H-benzochromenone, pharachromenone, which was characterized as methyl-2″-(7-hydroxy-4-(5'-methylpent-5'-en-1'-yl-oxy-methyl)-2-oxo-2H-benzo[h]chromen-5-yl-methyl)-butanoate by mass and nuclear magnetic resonance spectral experiments. Pharachromenone revealed effective biopotency against 5-lipoxygenase (IC50 1.85mM) and cyclooxygenase-2 (IC50 0.52mM) than that displayed by nonsteroidal anti-inflammatory drug ibuprofen (IC50 4.36mM, p<.05). Promising antioxidant property for pharachromenone (IC50 1.42-1.61mM) compared with those exhibited by antioxidative agents butylated hydroxyl anisole (BHA) and α-tocopherol (IC50 1.40-1.90mM) could conceivably validate its dual inhibition potential against 5-lipoxygenase and cyclooxygenase-2. Greater electronic parameters, lesser steric bulkiness, along with acceptable lipophilic-hydrophobic balance significantly contributed toward its promising anti-inflammatory activities. Molecular docking studies showing significantly greater inhibition constant (Ki) 8.24nM and binding energy (-11.03kcal/mol) of pharachromenone than the standard ibuprofen (Ki 4.65μM, binding energy -7.27kcal/mol) at the binding site of 5-lipoxygenase recognized its noncompetitive binding, which could describe the promising anti-inflammatory potential. Pharachromenone could be developed as a functional food component against oxidative stress-related inflammatory disorders. PRACTICAL APPLICATIONS: The cuttlefish Sepia pharaonis (family Sepiidae) comprises a major share in the global fishery sector due to its culinary delicacy and nutritionally valued high-quality meat. Furthermore, cephalopod mollusks are gaining pharmaceutical acceptance as resources to derive bioactive compounds with therapeutic significance. Bioassay-guided chromatographic fractionation of crude extract of S. pharaonis could result in the isolation of a 2H-benzochromenone derivative, pharachromenone exhibiting potent antioxidant and anti-inflammatory properties. This study recognized the therapeutic potential of a marine cuttlefish-originated food constituent against inflammatory conditions, and could be anticipated as a high-value functional food lead to minimize oxidative stress-related inflammatory disorders.

An in vivo evaluation of anti-inflammatory, analgesic and anti-pyretic activities of newly synthesized 1, 2, 4 Triazole derivatives

BackgroundIn recent years, 1, 2, 4-triazole and its derivatives have been reported to be pharmacologically significant scaffolds. They possess analgesic, anti-tubercular, anti-inflammatory, anti-convulsant, anti-oxidant, anti-fungal, anti-cancer, anxiolytic and anti-depressant activity. This study was designed and conducted to evaluate the potential anti-inflammatory, analgesic and antipyretic activities of Triazole derivatives.MethodsSwiss albino (male and female) mice weighing 20-30 g (10-24 weeks female), (5-14 weeks male) and Wister Kyoto rats (male and female) weighing 200-300 g (8-10 weeks old) were used for the present study. Anti-inflammatory activity was checked using Lambda carrageenan (λ) and egg albumin-induced paw edema models. Analgesic via Writhing Reflex induced by acetic acid and formalin, furthermore anti-pyretic activity was assessed by yeast induced pyrexia.ResultsBoth of the test compounds exhibited encouraging anti-inflammatory analgesic and antipyretic results when compared with standard drug ibuprofen. The maximum inhibition of edema for the compound (S)-1-(4-Amino-5-mercapto-4H-1,2,4-triazole-3-yl) ethanol [3] was found to be (91)% as compared to reference drug ibuprofen (82)%, while (S)-1-(6-Phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)ethanol [5e] showed equipotent results to ibuprofen (81)%. The derivatives were also screened for their anti-nociceptive activity by Acetic acid writhing and tail immersion test. Compound 3 showed a significant reduction in wriths (83)% as compared to standard drug ibuprofen 71.5% and [5] showed comparable results to ibuprofen by exhibiting 70% reduction in writh at the same dose as that of standard drug, moreover, there were no signs of toxicity being observed after administration of high doses of test compounds to mice.ConclusionsIt is evident from the results that compounds 3(compound A) and 5(compound B) are a potential candidate for anti-inflammatory, analgesic and anti-pyretic and the scaffold could be used for further structural modifications. Further studies would help to evaluate their molecular mechanism of action regarding these beneficial activities.

CYP2C9*3 Increases the Ibuprofen Response of Hemodynamically Significant Patent Ductus Arteriosus in the Infants with Gestational Age of More Than 30 Weeks.

The online version contains supplementary material available at 10.1007/s43657-021-00028-9.

PENGARUH PENAMBAHAN POLIETILEN GLIKOL 6000 PADA TABLET IBUPROFEN DISPERSI PADAT TERHADAP ABSORBSI IBUPROFEN SECARA IN SITU

Drug absorption can be decided by various methods, namely in vitro methods, in situ methods, and in vivo methods. The in situ method is a procedure that is very close to the in vivo method. The aim of this study was to identify the effect of accumulation of polyethylene glycol 6000 (PEG 6000) on solid dispersion of ibuprofen tablets on the in-situ absorption of the drug. This research was conducted through an experiment to determine the effect of adding polyethylene glycol 6000 to the absorption of ibuprofen in situ by flowing the solution from solid dispersion ibuprofen tablets, solutions from generic ibuprofen tablets and standard ibuprofen solutions. The solid dispersion system was carried out by melting ibuprofen and polyethylene glycol 6000 in a ratio of 1:05. The drug solution was flowed through the lumen of the small intestine of male rats. Unabsorbed ibuprofen was measured by an ultraviolet spectrophotometer at a wavelength of 225.5 nm. Next, the absorbed level of ibuprofen was calculated. The results showed that ibuprofen from solid dispersion tablets was absorbed more than ibuprofen from generic tablets and standard ibuprofen. It can be concluded that polyethylene glycol 6000 has an effect on the absorption of ibuprofen in situ.