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IUBMB Life Dec 2014Oxicams are a class of nonsteroidal anti-inflammatory drugs (NSAIDs) structurally related to the enolic acid class of 4-hydroxy-1,2-benzothiazine carboxamides. They are... (Review)
Review
Oxicams are a class of nonsteroidal anti-inflammatory drugs (NSAIDs) structurally related to the enolic acid class of 4-hydroxy-1,2-benzothiazine carboxamides. They are used clinically to treat both acute and chronic inflammation by inhibiting the activity of the two cyclooxygenase (COX) isoforms, COX-1 and COX-2. Oxicams are structurally distinct from all other NSAIDs, exhibiting a novel binding pose in the COX active site. The 4-hydroxyl group on the thiazine ring partners with Ser-530 via hydrogen bonding while two coordinated water molecules mediate a polar interaction between the oxicam and COX. The rotation of Leu-531 in the complex opens a new pocket, which is not used for binding other NSAIDs to the enzyme. This structure provides the basis for understanding documented structure-activity relationships within the oxicam class. In addition, from the oxicam template, a series of potent microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors represents a new direction for drug development. Here, we review the major route of oxicam synthesis and structure-activity for COX inhibition, as well as recent advances in oxicam-mediated mPGES-1 inhibition.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Inflammation; Intramolecular Oxidoreductases; Meloxicam; Piroxicam; Prostaglandin-E Synthases; Thiazines; Thiazoles
PubMed: 25537198
DOI: 10.1002/iub.1334 -
ACS Omega Nov 2023Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation, joint tissue damage, pain, and synovitis. It leads to deformity of joints,...
Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation, joint tissue damage, pain, and synovitis. It leads to deformity of joints, disability, and even premature death. Markers of inflammation are highly expressed in synovium fluid and serum of arthritic patients and play an important role in the pathophysiology of RA. These transcription factors promote the fabrication of type I interferons and inflammatory cytokines. In RA, degradation of synovial cartilage and bone results from stimulation of proinflammatory cytokines. Citronellol (Ct), a monoterpene alcohol, is found in citrus fruits and essential oils of many aromatic plants. It possesses numerous pharmacological properties such as antioxidant activity and potential antinociceptive and anti-inflammatory effects. Keeping in view the significant anti-inflammatory role of Ct, a trial of 28 days was conducted. Ct was administered orally at three different doses (25, 50, and 100) mg/kg in Freund's adjuvant-induced arthritic rats, and the results were compared with piroxicam, chosen as the standard drug. The antiarthritic activity of the compound was evaluated through measurements of arthritic scoring and plethysmometry before and after treatment. The blood biochemical and hematological parameters and histopathological analyses were performed. Additionally, qPCR was conducted to analyze the mRNA expression levels of TNF-α, IL-1β, NF-κB, MMP3, IL-6, and IL-4 in the blood. ELISA was performed to evaluate the levels of PGE2. The results demonstrated that Ct showed significant results at all doses, but the highest dose proved to be most significant in terms of decreasing arthritic scoring and paw edema, indicating the antiarthritic potential of Ct. Furthermore, the compound was found to downregulate all the proinflammatory cytokines (TNF-α, IL-1β, NF-κB, MMP3, and IL-6) and upregulate the anti-inflammatory cytokine (IL-4). The levels of PGE2 were also reduced which further supported the antiarthritic effects of Ct and validated it as a potential antiarthritic candidate.
PubMed: 38046326
DOI: 10.1021/acsomega.3c06374 -
Ethiopian Journal of Health Sciences Jul 2022Premenstrual syndrome (PMS) is a physiologic process in women where mood swing is one of the symptoms influencing the psycho-emotional, physical, and behavioral...
BACKGROUND
Premenstrual syndrome (PMS) is a physiologic process in women where mood swing is one of the symptoms influencing the psycho-emotional, physical, and behavioral reactions exhibited by women during menstruation. This study elucidates the effect of mood swing, confounding factors and healthcare-seeking behaviors of women in an educational environment.
METHODS
Exactly 328 women who were within reproductive ages 16 and 35 years participated in this study. A survey method was adopted; validated and standardized questionnaires were administered to confidentially assess the effect of mood swing via PMS. All data were analyzed with SPSS 25.0; descriptive method was adopted and results were expressed in percentages.
RESULTS
Mood swing was discovered as a symptom overlapping with psycho-emotional, physical, and behavioral symptoms during menstruation. The overall PMS prevalence was 67.4% while PMDD prevalence was 25.6%. Psycho-emotional symptoms: anger, irritability, depression. Physical symptoms: coldness, paleness, food craving, breast tenderness, digestive changes. Behavioral symptoms: social withdrawal, nocturnal social activity, absenteeism, poor work or academic performance, increased libido. Confounding factors include stress, gynecological conditions such as endometriosis, uterine fibroid, ovarian cyst, pelvic adhesion, and polycystic ovarian syndrome. Also, 22.9% had a family history of bipolar disorder (BD) while 30.2% had previous diagnosis. Severe pain was a major factor for seeking treatment; Paracetamol, and Piroxicam were frequently used drugs.
CONCLUSIONS
Severe PMS triggers mood swing and can badly affect academic or work activities; victims either endure the pain due to socio-cultural and financial factors or take unsuitable medications where abuse is inevitable.
Topics: Adolescent; Adult; Emotions; Female; Humans; Menstruation; Pain; Premenstrual Syndrome; Substance-Related Disorders; Surveys and Questionnaires; Young Adult
PubMed: 35950064
DOI: 10.4314/ejhs.v32i4.3 -
Journal of Pharmacology &... 2015To investigate the antidepressant-like effect of piroxicam with a focus on serotonergic neurotransmission.
OBJECTIVE
To investigate the antidepressant-like effect of piroxicam with a focus on serotonergic neurotransmission.
MATERIALS AND METHODS
Rats were randomly distributed into the following groups: 0.9% saline control; 3 mg/kg pizotifen; 10 mg/kg sertraline; 10 mg/kg piroxicam; 10 mg/kg sertraline + 10 mg/kg piroxicam; 10 mg/kg sertraline + 3 mg/kg pizotifen; and 10 mg/kg piroxicam + 3 mg/kg pizotifen. All the drugs were dissolved in 0.9% saline. Three administrations of the drugs (piroxicam and sertraline) were performed 1, 5 and 24 h before testing the animals in the open field followed by the forced swim test (FST). Piroxicam and sertraline were administered orally by gavage and pizotifen was administered intraperitoneally 30 min before gavage. Immediately after the FST, the hippocampi were rapidly dissected for neurochemical analysis in high-performance liquid chromatography.
RESULTS
Acute treatment with piroxicam promoted an antidepressant-like effect in the FST, which was associated with an increase in serotonin levels in the hippocampus. This effect was potentiated in the piroxicam + sertraline group but counteracted by administration of the non-selective serotonin receptor antagonist pizotifen.
CONCLUSION
These results suggest that the antidepressant-like effect of piroxicam in the FST is mediated by the serotonin system; however, by different mechanisms from those of sertraline.
PubMed: 25709346
DOI: 10.4103/0976-500X.149133 -
RSC Advances Sep 2023Piroxicam and naproxen are well-known non-steroidal anti-inflammatory drugs that are frequently detected in aquatic environments due to their widespread usage and...
Piroxicam and naproxen are well-known non-steroidal anti-inflammatory drugs that are frequently detected in aquatic environments due to their widespread usage and improper disposal practices. This research investigates the photocatalytic degradation of these drugs by using CeO nanoparticles. The nanoparticles were synthesized by using plant extract and were characterized through various characterization techniques such as UV-visible spectroscopy, FTIR spectroscopy, SEM, EDX, and XRD. The photocatalytic degradation of piroxicam and naproxen using CeO nanoparticles led to the efficient removal of these pharmaceutical drugs in a short time duration with photodegradation efficiencies of 89% and 97% for naproxen and piroxicam, respectively. The photodegradation reaction was found to follow pseudo-order first-order kinetics. The recyclability of the catalyst was also studied for up to six cycles where the degradation efficiency was maintained at 100% till the 2nd cycle and was decreased by 11 and 13% for piroxicam and naproxen respectively after the 6th cycle. The current work focused on the achievement of sustainable development goals (SDGs) for water purification environmentally benign nanoparticles to remedy water pollution as it is the most prevalent issue in developed and underdeveloped countries throughout the world.
PubMed: 37746332
DOI: 10.1039/d3ra04185a -
The Journal of Veterinary Medical... Apr 2021A 13-year-old intact Pomeranian bitch presented with a 2-month history of abdominal distension and anorexia. Ultrasonography and computed tomography revealed a large...
A 13-year-old intact Pomeranian bitch presented with a 2-month history of abdominal distension and anorexia. Ultrasonography and computed tomography revealed a large tumor in the abdominal cavity without metastases. The tumor was surgically resected and histopathologically characterized by spindle-shaped to atypical-shaped neoplastic cells with basophilic stroma in the omental adipose tissue. Immunohistochemistry revealed that the neoplastic cells were positive for vimentin but negative for cytokeratin, S-100 protein, and α-SMA. The bitch was diagnosed as a myxosarcoma arising from the greater omentum. Postoperatively, metronomic chemotherapy with cyclophosphamide and piroxicam was initiated. The tumor recurred on postoperative day 49. Although the bitch died 102 days after the initial examination, her general condition was maintained until death.
Topics: Adipose Tissue; Animals; Dog Diseases; Dogs; Female; Immunohistochemistry; Myxosarcoma; Neoplasm Recurrence, Local; Omentum
PubMed: 33504735
DOI: 10.1292/jvms.20-0509 -
Journal of the American Chemical Society Apr 2022Determination of the three-dimensional atomic-level structure of powdered solids is one of the key goals in current chemistry. Solid-state NMR chemical shifts can be...
Determination of the three-dimensional atomic-level structure of powdered solids is one of the key goals in current chemistry. Solid-state NMR chemical shifts can be used to solve this problem, but they are limited by the high computational cost associated with crystal structure prediction methods and density functional theory chemical shift calculations. Here, we successfully determine the crystal structures of ampicillin, piroxicam, cocaine, and two polymorphs of the drug molecule AZD8329 using on-the-fly generated machine-learned isotropic chemical shifts to directly guide a Monte Carlo-based structure determination process starting from a random gas-phase conformation.
Topics: Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Monte Carlo Method
PubMed: 35416661
DOI: 10.1021/jacs.1c13733 -
Advanced Pharmaceutical Bulletin Sep 2017Cocrystallisation of drug with coformers is a promising approach to alter the solid sate properties of drug substances like solubility and dissolution. The objective of...
Cocrystallisation of drug with coformers is a promising approach to alter the solid sate properties of drug substances like solubility and dissolution. The objective of the present work was to prepare, formulate and evaluate the piroxicam cocrystal by screening various coformers. Cocrystals of piroxicam were prepared by dry grinding method. The melting point and solubility of crystalline phase was determined. The potential cocrystal was characterized by DSC, IR, XRPD. Other pharmaceutical properties like solubility and dissolution rate were also evaluated. Orodispersible tablets of piroxicam cocrystal were formulated, optimized and evaluated using 3 factorial design. Cocrystals of piroxicam-sodium acetate revealed the variation in melting points and solubility. The cocrystals were obtained in 1:1 ratio with sodium acetate. The analysis of Infrared explicitly indicated the shifting of characteristic bands of piroxicam. The X-Ray Powder Diffraction pattern denoted the crystallinity of cocrystals and noteworthy difference in 2θ value of intense peaks. Differential scanning calorimetry spectra of cocrystals indicated altered endotherms corresponding to melting point. The pH solubility profile of piroxicam showed sigmoidal curve, which authenticated the pKa-dependent solubility. Piroxicam cocrystals also exhibited a similar pH-solubility profile. The cocrystals exhibited faster dissolution rate owing to cocrystallization as evident from 30% increase in the extent of dissolution. The orodispersible tablets of piroxicam cocrystals were successfully prepared by direct compression method using crosscarmelose sodium as superdisintegrant with improved disintegration time (30 sec) and dissolution rate. The piroxicam cocrystal with modified properties was prepared with sodium acetate and formulated as orodispersible tablets having faster disintegration and greater dissolution rate.
PubMed: 29071222
DOI: 10.15171/apb.2017.048 -
Purinergic Signalling Jun 2021Glioblastoma (GBM) is the most malignant and deadly brain tumor. GBM cells overexpress the CD73 enzyme, which controls the level of extracellular adenosine, an...
Glioblastoma (GBM) is the most malignant and deadly brain tumor. GBM cells overexpress the CD73 enzyme, which controls the level of extracellular adenosine, an immunosuppressive molecule. Studies have shown that some nonsteroidal anti-inflammatory drugs (NSAIDs) and methotrexate (MTX) have antiproliferative and modulatory effects on CD73 in vitro and in vivo. However, it remains unclear whether the antiproliferative effects of MTX and NSAIDS in GBM cells are mediated by increases in CD73 expression and adenosine formation. The aim of this study was to evaluate the effect of the NSAIDs, naproxen, piroxicam, meloxicam, ibuprofen, sodium diclofenac, acetylsalicylic acid, nimesulide, and ketoprofen on CD73 expression in GBM and mononuclear cells. In addition, we sought to understand whether the effects of MTX may be mediated by CD73 expression and activity. Cell viability and CD73 expression were evaluated in C6 and mononuclear cells after exposure to NSAIDs. For analysis of the mechanism of action of MTX, GBM cells were treated with APCP (CD73 inhibitor), dipyridamole (inhibitor of adenosine uptake), ABT-702 (adenosine kinase enzyme inhibitor), or caffeine (P1 adenosine receptor antagonist), before treatment with MTX and AMP, in the presence or not of mononuclear cells. In summary, only MTX increased the expression of CD73 in GBM cells decreasing cells viability by mechanisms independent of the adenosinergic system. Further studies are needed to understand the role of MTX in the GBM microenvironment.
Topics: 5'-Nucleotidase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites, Antineoplastic; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Glioblastoma; Glioma; Male; Methotrexate; Monocytes; Rats; Rats, Wistar
PubMed: 33745072
DOI: 10.1007/s11302-021-09775-w -
Biomolecules Oct 2021Heat shock proteins HSPA1/Hsp70α and HSP90AA1/Hsp90α are crucial for cancer growth but their expression pattern in colorectal polyps or whether they can be modulated...
Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring.
Heat shock proteins HSPA1/Hsp70α and HSP90AA1/Hsp90α are crucial for cancer growth but their expression pattern in colorectal polyps or whether they can be modulated by oxicams is unknown. We quantified (RTqPCR) and expression in 50 polyp-normal pairs in relation to polyp malignancy potential and examined the effect of piroxicam, meloxicam and five novel analogues on HSPA1 and HSP90AA1 expression (mRNA/protein) in colorectal adenocarcinoma lines. and were upregulated in polyps by 3- and 2.9-fold. Expression ratios were higher in polyps with higher dysplasia grade and dominant villous growth pattern, mostly a result of diminished gene expression in normal tissue. Classic oxicams had negligible/non-significant effect on HSP expression. Their most effective analogue inhibited HSPA1 protein and gene by 2.5-fold and 5.7-fold in Caco-2 and by 11.5-fold and 6.8-fold in HCT116 and HSPA1 protein in HT-29 by 1.9-fold. It downregulated HSP90AA1 protein and gene by 1.9-fold and 3.7-fold in Caco-2 and by 2-fold and 5.0-fold in HCT116. and are upregulated in colorectal polyps reflecting their potential for malignancy. HSPA1 in cancer cells and, to lesser degree, HSP90AA1 can be reduced by oxicam analogues with thiazine ring substituted via propylene linker by arylpiperazine pharmacophore with fluorine substituents and by benzoyl moiety.
Topics: Caco-2 Cells; Colonic Polyps; Colorectal Neoplasms; Heat-Shock Proteins; Humans; Thiazines
PubMed: 34827586
DOI: 10.3390/biom11111588