Displaying publications 1 - 20 of 28 in total

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  1. Abdelgawad MA, Bakr RB, Ahmad W, Al-Sanea MM, Elshemy HAH
    Bioorg Chem, 2019 11;92:103218.
    PMID: 31536956 DOI: 10.1016/j.bioorg.2019.103218
    To enhance the cytotoxicity of benzimidazole and/or benzoxazole core, the benzimidazole/benzoxazole azo-pyrimidine were synthesized through diazo-coupling of 3-aminophenybenzimidazole (6a) or 3-aminophenylbenzoxazole (6b) with diethyl malonate. The new azo-molanates 6a&b mixed with urea in sodium ethoxide to afford the benzimidazolo/benzoxazolopyrimidine 7a&b. The structure elucidation of new synthesized targets was proved using spectroscopic techniques NMR, IR and elemental analysis. The cytoxicity screening had been carried out against five cancer cell lines: prostate cancer (PC-3), lung cancer (A-549), breast cancer (MCF-7), pancreas cancer (PaCa-2) and colon cancer (HT-29). Furthermore, the antioxidant activity, phospholipase A2-V and cyclooxygenases inhibitory activities of the target compounds 7a&b were evaluated and the new compounds showed potent activity (cytotoxicity IC50 range from 4.3 to 9.2 µm, antioxidant activity from 40% to 80%, COXs or LOX inhibitory activity from 1.92 µM to 8.21 µM). The docking of 7a&b was made to confirm the mechanism of action.
    Matched MeSH terms: Cyclooxygenase 1/metabolism
  2. Abdelwahab SI, Mohan S, Abdulla MA, Sukari MA, Abdul AB, Taha MM, et al.
    J Ethnopharmacol, 2011 Sep 2;137(2):963-70.
    PMID: 21771650 DOI: 10.1016/j.jep.2011.07.010
    Boesenbergia rotunda (L) Mansf. has been used for the treatment of gastrointestinal disorders including peptic ulcer. In the current study we aimed to investiagte the anti-ulcer activities of methanolic extract of B. rotunda (MEBR) and its main active compound, pinostrobin on ethanol-induced ulcer in rats. The possible involevement of lipid peroxidation, nitric oxide, cyclooxygenases and free radical scavenging mechanisms also has been investigated.
    Matched MeSH terms: Cyclooxygenase 1/metabolism
  3. Ahmad NS, Tan TL, Arifin KT, Ngah WZW, Yusof YAM
    PLoS One, 2020;15(3):e0230285.
    PMID: 32160261 DOI: 10.1371/journal.pone.0230285
    The aim of this study was to determine the association between secretory phospholipase A2 group IIA (sPLA2-IIA) and eicosanoid pathway metabolites in patients with bacterial sepsis syndrome (BSS). Levels of sPLA2-IIA, eicosanoids prostaglandin (PG)E2, PGD synthase were quantified in the sera from patients confirmed to have bacterial sepsis (BS; N = 45), bacterial severe sepsis/septic shock (BSS/SS; N = 35) and healthy subjects (N = 45). Cyclooxygenase (COX)-1 and COX-2 activities were analyzed from cell lysate. Serum levels of sPLA2-IIA, PGE2, and PGDS increased significantly in patients with BS and BSS/SS compared to healthy subjects (p<0.05). COX-2 activity was significantly increased in patients with BS compared to healthy subjects (p<0.05), but not COX-1 activity. Binary logistic regression analysis showed that sPLA2-IIA and PGE2 were independent factors predicting BSS severity. In conclusion, high level of sPLA2-IIA is associated with eicosanoid metabolism in patients with BSS.
    Matched MeSH terms: Cyclooxygenase 1/blood
  4. Bukhari SN, Zhang X, Jantan I, Zhu HL, Amjad MW, Masand VH
    Chem Biol Drug Des, 2015 Jun;85(6):729-42.
    PMID: 25328063 DOI: 10.1111/cbdd.12457
    A novel series of 1,3-diphenyl-2-propen-1-one (chalcone) derivatives was synthesized by a simple, eco-friendly, and efficient Claisen-Schmidt condensation reaction and used as precursors for the synthesis of new pyrazoline derivatives. All the synthesized compounds were screened for anti-inflammatory related activities such as inhibition of phospholipase A(2) (PLA(2)), cyclooxygenases (COX-1 and COX-2), IL-6, and TNF-α. The results of the above studies show that the compounds synthesized are effective inhibitors of above pro-inflammatory enzymes and cytokines. Overall, the results of the studies reveal that the pyrazolines with chlorophenyl substitution (1b-6b) seem to be important for inhibition of enzymes and cytokines. Molecular docking experiments were performed to clarify the molecular aspects of the observed COX-inhibitory activities of the investigated compounds.
    Matched MeSH terms: Cyclooxygenase 1/metabolism
  5. Bukhari SN, Lauro G, Jantan I, Fei Chee C, Amjad MW, Bifulco G, et al.
    Future Med Chem, 2016 Oct;8(16):1953-1967.
    PMID: 27654499
    In present study, the anti-inflammatory activities of a new series of benzimidazole derivatives were studied, investigating their inhibition of secretory phospholipase A2, lipoxygenase, COXs and lipopolysaccharide-induced secretion of TNF-α and IL-6 in mouse RAW264.7 macrophages.
    Matched MeSH terms: Cyclooxygenase 1
  6. Fukuda M, Uni S, Otsuka Y, Eshita Y, Nakatani J, Ihara K, et al.
    Parasitol Int, 2015 Dec;64(6):519-21.
    PMID: 26209456 DOI: 10.1016/j.parint.2015.07.006
    A case of zoonotic onchocercosis has been found in a resident who lived in Iizuka City, Fukuoka Prefecture, Japan for some time. A 24-year-old male developed a painful nodule on the middle finger of his right hand. The nodule was surgically removed from the vagina fibrosa tendinis of the finger at Beppu Medical Center, Beppu City, Oita Prefecture in 2012. The causative agent was identified as a female Onchocerca dewittei japonica based on its histopathological characteristics. The identity of the filarioid has been confirmed by sequencing the cox1 gene. The present study indicates that the zoonotic onchocercosis caused by O. dewittei japonica has been concentrated in northeast Kyushu.
    Matched MeSH terms: Cyclooxygenase 1
  7. Fukuda M, Uni S, Igari T, Utsumi Y, Otsuka Y, Nakatani J, et al.
    Parasitol Int, 2019 Oct;72:101943.
    PMID: 31220633 DOI: 10.1016/j.parint.2019.101943
    A 73-year-old man living in Kawamata-machi, Fukushima Prefecture, Northeastern Honshu, Japan, visited a hospital with complaints of a subcutaneous swelling that had developed on the back of his left hand. The nodule was surgically removed from the vagina fibrosa tendinis of his left forefinger. Based on the histopathological characteristics, the causative agent of this nodule was identified as a female Onchocerca dewittei japonica (Spirurida: Onchocercidae). The species identification was confirmed by cox1 gene sequencing of the worm tissues from paraffin-embedded sections of the nodule. Although 11 cases of zoonotic onchocercosis have previously been recorded in Kyushu and Western Honshu, Japan, the present findings represent the first human case of infection with O. dewittei japonica in Northeastern Honshu, Japan.
    Matched MeSH terms: Cyclooxygenase 1/genetics
  8. George A, Chinnappan S, Chintamaneni M, Kotak C V, Choudhary Y, Kueper T, et al.
    PMID: 25252832 DOI: 10.1186/1472-6882-14-355
    The study was aimed to evaluate the anti-inflammatory activity of ethanolic and aqueous extracts of Polygonum minus (Huds) using in vitro and in vivo approaches.
    Matched MeSH terms: Cyclooxygenase 1/analysis; Cyclooxygenase 1/metabolism
  9. Hamsin DE, Hamid RA, Yazan LS, Taib CN, Yeong LT
    PMID: 24641961 DOI: 10.1186/1472-6882-14-102
    In our previous studies conducted on Ardisia crispa roots, it was shown that Ardisia crispa root inhibited inflammation-induced angiogenesis in vivo. The present study was conducted to identify whether the anti-angiogenic properties of Ardisia crispa roots was partly due to either cyclooxygenase (COX) or/and lipoxygenase (LOX) activity inhibition in separate in vitro studies.
    Matched MeSH terms: Cyclooxygenase 1/metabolism
  10. Hu W, Yu XG, Wu S, Tan LP, Song MR, Abdulahi AY, et al.
    J Helminthol, 2016 Jul;90(4):392-7.
    PMID: 26123649 DOI: 10.1017/S0022149X15000413
    Ancylostoma ceylanicum is a common zoonotic nematode. Cats act as natural reservoirs of the hookworm and are involved in transmitting infection to humans, thus posing a potential risk to public health. The prevalence of feline A. ceylanicum in Guangzhou (South China) was surveyed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In total, 112 faecal samples were examined; 34.8% (39/112) and 43.8% (49/112) samples were positive with hookworms by microscopy and PCR method, respectively. Among them, 40.8% of samples harboured A. ceylanicum. Twelve positive A. ceylanicum samples were selected randomly and used for cox 1 sequence analysis. Sequencing results revealed that they had 97-99% similarity with A. ceylanicum cox 1 gene sequences deposited in GenBank. A phylogenetic tree showed that A. ceylanicum isolates were divided into two groups: one comprising four isolates from Guangzhou (South China), and the other comprising those from Malaysia, Cambodia and Guangzhou. In the latter group, all A. ceylanicum isolates from Guangzhou were clustered into a minor group again. The results indicate that the high prevalence of A. ceylanicum in stray cats in South China poses a potential risk of hookworm transmission from pet cats to humans, and that A. ceylanicum may be a species complex worldwide.
    Matched MeSH terms: Cyclooxygenase 1/genetics*
  11. Jalil NJ, Bannur Z, Derahman A, Maskon O, Darinah N, Hamidi H, et al.
    J Pharm Pharm Sci, 2015;18(3):474-83.
    PMID: 26517138
    PURPOSE:   Enzymes potentially responsible for the pharmacokinetic variations of aspirin include cyclooxygenase-1 (COX-1), UDP-glucuronosyltransferase (UGT1A6) and P450 (CYP) (CYP2C9). We therefore aimed to determine the types and frequencies of variants of COX-1 (A-842G), UGT1A6 (UGT1A6*2; A541G and UGT1A6*3; A522C) and CYP2C9 (CYP2C9*3; A1075C) in the three major ethnic groups in Malaysia. In addition, the role of these polymorphisms on aspirin-induced gastritis among the patients was investigated.

    METHODS: A total of 165 patients with cardiovascular disease who were treated with 75-150 mg daily dose of aspirin and 300 healthy volunteers were recruited. DNA was extracted from the blood samples and genotyped for COX-1 (A-842G), UGT1A6 (UGT1A6*2 and UGT1A6*3) and CYP2C9 (CYP2C9*3; A1075C) using allele specific polymerase chain reaction (AS-PCR).

    RESULTS: Variants UGT1A6*2,*3 and CYP2C9*3 were detected in relatively high percentage of 22.83%, 30.0% and 6.50%, respectively; while COX-1 (A-842G) was absent. The genotype frequencies for UGT1A6*2 and *3 were significantly different between Indians and Malays or Chinese. The level of bilirubin among patients with different genotypes of UGT1A6 was significantly different (p-value < 0.05). In addition, CYP2C9*3 was found to be associated with gastritis with an odd ratio of 6.8 (95 % Cl OR: 1.39 - 33.19; P = 0.033).

    CONCLUSION: Screening of patients with defective genetic variants of UGT1A6 and CYP2C9*3 helps in identifying patients at risk of aspirin induced gastritis. However, a randomised clinical study of bigger sample size would be needed before it is translated to clinical use.

    Matched MeSH terms: Cyclooxygenase 1/genetics*
  12. Jeyamogan S, Khan NA, Anwar A, Shah MR, Siddiqui R
    SAGE Open Med, 2018;6:2050312118781962.
    PMID: 30034805 DOI: 10.1177/2050312118781962
    Objectives: To synthesize novel compounds belonging to Benzodioxane, Naphthalene diimide, Aminophenol derivatives and Porphyrin classes and test their potential anticancer properties.

    Methods: Several compounds were synthesized and their molecular identity was confirmed using nuclear magnetic resonance. Potential anticancer properties were determined using cytopathogenicity assays and growth inhibition assays using cervical cancer cells (HeLa). Cells were incubated with different concentrations of compounds belonging to Benzodioxane, Naphthalene diimide, Aminophenol derivatives and Porphyrins and effects were determined. HeLa cells cytopathogenicity was determined by measuring lactate dehydrogenase release using cytotoxicity detection assay. Growth inhibition assays were performed by incubating 50% semi-confluent HeLa cells with Benzodioxane, Naphthalene diimide, Aminophenol derivatives and Porphyrin compounds and HeLa cell proliferation was observed. Growth inhibition and host cell death were compared in the presence and absence of drugs.

    Results: Cytopathogenicity assays showed that the selected compounds were cytotoxic against HeLa cells, killing up to 90% of cells. Growth inhibition assays exhibited 100% growth inhibition. These effects are likely via oxidative stress, production of reactive oxygen species, changes in cytosolic and intracellular calcium/adenine nucleotide homeostasis, inhibition of ribonucleotide reductase/cyclooxygenase and/or glutathione depletion.

    Conclusions: Benzodioxane, Naphthalene diimide, Aminophenol derivatives and Porphyrins exhibited potent anticancer properties. These findings are promising and should pave the way in the rationale development of anticancer drugs. Using different cancer cell lines, future studies will determine their potential as anti-tumour agents as well as their precise molecular mode of action.

    Matched MeSH terms: Cyclooxygenase 1
  13. Kamal A, Nazari V M, Yaseen M, Iqbal MA, Ahamed MBK, Majid ASA, et al.
    Bioorg Chem, 2019 09;90:103042.
    PMID: 31226469 DOI: 10.1016/j.bioorg.2019.103042
    Three benzimidazolium salts (III-V) and respective selenium adducts (VI-VIII) were designed, synthesized and characterized by various analytical techniques (FT-IR and NMR 1H, 13C). Selected salts and respective selenium N-Heterocyclic carbenes (selenium-NHC) adducts were tested in vitro against Cervical Cancer Cell line (Hela), Breast Adenocarcinoma cell line (MCF-7), Retinal Ganglion Cell line (RGC-5) and Mouse Melanoma Cell line (B16F10) using MTT assay and the results were compared with standard drug 5-Fluorouracil. Se-NHC compounds and azolium salts showed significant anticancer potential. Molecular docking studies of compounds (VI, VII and VIII) showed strong binding energies and ligand affinity toward following angiogenic factors: VEGF-A (vascular endothelial growth factor A), EGF (human epidermal growth factor), HIF (Hypoxia-inducible factor) and COX-1 (Cyclooxygenase-1) suggesting that the anticancer activity of adducts (VI, VII and VIII) may be due to their strong anti-angiogenic effect. In addition, compounds III-VIII were screened for their antibacterial and antifungal potential. Adduct VI was found to be potent anti-fungal agent against A. Niger with zone of inhibition (ZI) value 27.01 ± 0.251 mm which is better than standard drug Clotrimazole tested in parallel.
    Matched MeSH terms: Cyclooxygenase 1
  14. Lee KH, Abas F, Alitheen NB, Shaari K, Lajis NH, Ahmad S
    Molecules, 2011 Nov 23;16(11):9728-38.
    PMID: 22113581 DOI: 10.3390/molecules16119728
    Our preliminary screening had shown that the curcumin derivative [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] or BDMC33 exhibited improved anti-inflammatory activity by inhibiting nitric oxide synthesis in activated macrophage cells. In this study, we further investigated the anti-inflammatory properties of BDMC33 on PGE(2 )synthesis and cyclooxygenase (COX) expression in IFN-γ/LPS-stimulated macrophages. We found that BDMC33 significantly inhibited PGE(2) synthesis in a concentration-dependent manner albeit at a low inhibition level with an IC(50) value of 47.33 ± 1.00 µM. Interestingly, the PGE(2) inhibitory activity of BDMC33 is not attributed to inhibition of the COX enzyme activities, but rather BDMC33 selectively down-regulated the expression of COX-2. In addition, BDMC33 modulates the COX expression by sustaining the constitutively COX-1 expression in IFN-γ/LPS-treated macrophage cells. Collectively, the experimental data suggest an immunodulatory action of BDMC33 on PGE(2) synthesis and COX expression, making it a possible treatment for inflammatory disorders with minimal gastrointestinal-related side effects.
    Matched MeSH terms: Cyclooxygenase 1/genetics; Cyclooxygenase 1/metabolism
  15. Mohd Sairazi NS, Sirajudeen KNS, Muzaimi M, Mummedy S, Asari MA, Sulaiman SA
    PMID: 30108663 DOI: 10.1155/2018/7287820
    The protective effect of tualang honey (TH) on neuroinflammation and caspase-3 activity in rat cerebral cortex, cerebellum, and brainstem after kainic acid- (KA-) induced status epilepticus was investigated. Male Sprague-Dawley rats were pretreated orally with TH (1.0 g/kg body weight) five times at 12 h intervals. KA (15 mg/kg body weight) was injected subcutaneously 30 min after last oral treatment. Rats were sacrificed at 2 h, 24 h, and 48 h after KA administration. Neuroinflammation markers and caspase-3 activity were analyzed in different brain regions 2 h, 24 h, and 48 h after KA administration. Administration of KA induced epileptic seizures. KA caused significant (p < 0.05) increase in the level of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), glial fibrillary acidic protein (GFAP), allograft inflammatory factor 1 (AIF-1), and cyclooxygenase-2 (COX-2) and increase in the caspase-3 activity in the rat cerebral cortex, cerebellum, and brainstem at multiple time points. Pretreatment with TH significantly (p < 0.05) reduced the elevation of TNF-α, IL-1β, GFAP, AIF-1, and COX-2 level in those brain regions at multiple time points and attenuated the increased caspase-3 activity in the cerebral cortex. In conclusion, TH reduced neuroinflammation and caspase-3 activity after kainic acid- (KA-) induced status epilepticus.
    Matched MeSH terms: Cyclooxygenase 1
  16. Muhammad A, Khan B, Iqbal Z, Khan AZ, Khan I, Khan K, et al.
    ACS Omega, 2019 Sep 03;4(10):14188-14192.
    PMID: 31508540 DOI: 10.1021/acsomega.9b01041
    The antipyretic potential of viscosine, a natural product isolated from the medicinal plant Dodonaea viscosa, was investigated using yeast-induced pyrexia rat model, and its structure-activity relationship was investigated through molecular docking analyses with the target enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1). The in vivo antipyretic experiments showed a progressive dose-dependent reduction in body temperatures of the hyperthermic test animals when injected with viscosine. Comparison of docking analyses with target enzymes showed strongest bonding interactions (binding energy -17.34 kcal/mol) of viscosine with the active-site pocket of mPGES-1. These findings suggest that viscosine shows antipyretic properties by reducing the concentration of prostaglandin E2 in brain through its mPGES-1 inhibitory action and make it a potential lead compound for developing effective and safer antipyretic drugs for treating fever and related pathological conditions.
    Matched MeSH terms: Cyclooxygenase 1
  17. Ngah H, Hairon SM, Yaacob NM, Yusoff H
    Malays J Med Sci, 2019 Jul;26(4):70-78.
    PMID: 31496895 MyJurnal DOI: 10.21315/mjms2019.26.4.8
    Background: Death resulting from the acquired immunodeficiency syndrome (AIDS) is a worldwide concern. This study is aimed at determining the overall median survival time, and the prognostic factors of mortality among AIDS-infected patients in North-East Peninsular Malaysia.

    Methods: In 2018, a retrospective cohort study stretching from January to April was conducted. This study involved a review of data obtained from the National AIDS Registry. A total of 1,073 AIDS cases diagnosed from 1 January 2010 to 31 December 2014 were selected, and follow-up procedures were conducted until 31 March 2015 (a 3-month follow-up). The Kaplan-Meier plot and Cox's proportional hazard regression were used for data analyses.

    Results: 564 (52.5%) patients died due to AIDS, while the remaining 509 (47.4%) were censored. The overall median survival time was 11 months. The probability of survival in 1-year, 2-year, 3-year, 4-year and 5-year periods were 49.1%, 47.8%, 47.3%, 47.0% and 46.7%, respectively. Multiple Cox regression revealed that the significant prognostic factors were age 30-49 years [adjusted hazard ratio (Adj. HR) 1.57; 95% CI: 1.14, 2.16; P = 0.006], male (Adj. HR 1.39; 95% CI: 1.07, 1.79; P = 0.012), unemployed (Adj. HR 1.40; 95% CI: 1.12, 1.75; P = 0.003) and HIV-TB co-infection (Adj. HR 1.78; 95% CI: 1.37, 2.31; P < 0.001).

    Conclusion: The overall median survival time among AIDS patients in North-East Peninsular Malaysia was revealed to be short, in comparison to the other studies. The chances for survival can be improved with more emphasis on early detection (to ensure early treatment) and social support, particularly for HIV-TB co-infected patients, as well as for younger and unemployed patients.

    Matched MeSH terms: Cyclooxygenase 1
  18. Nurlaily, A., Noor Baitee, A.R., Musalmah, M.
    Medicine & Health, 2012;7(2):62-72.
    MyJurnal
    Keupayaan Centella asiatica (CA) untuk bertindak sebagai antioksidan dan agen anti-radang telah banyak dilaporkan. Namun begitu, kaedah pengekstrakan CA untuk memperoleh hasil yang terbaik masih dipersoalkan. Dalam kajian ini, kami menilai tiga kaedah pengekstrakan CA dan membuat perbandingan ekstrak dari segi aktiviti antioksidan dan anti-radang, dan juga kandungan sebatian bioaktif, asiaticoside dan madecassoside. Centella asiatica diekstrak menggunakan pelarut etanol, metanol dan juga air. Kandungan sebatian fenolik ekstrak diukur menggunakan kaedah reagen Folin-Ciocalteu. Kandungan asiaticoside dan madecassoside ditentukan dengan kaedah HPLC. Aktiviti antioksidan diukur dengan asai 2,2-diphenyl-1-picrylhydrazyl (DPPH) dan asai penurunan kuasa Ferric Reducing Antioxidant Power (FRAP). Aktiviti anti-radang ditentukan dengan kebolehan ekstrak untuk merencatkan enzim tapakjalan keradangan, COX-1 dan COX-2, serta kebolehan ekstrak melindungi sel fibroblas aruhan 12-O-tetradecanoylphorbol-13-acetate (TPA) daripada menghasilkan prostaglandin E2 (PGE2 ). Hasil kajian menunjukkan aras sebatian fenolik, asiaticoside dan madecassoside tertinggi dalam ekstrak etanol, diikuti metanol dan esktrak akues (masing-masing 17.76 g/100g, 15.52 g/100g, 13.16 g/100g untuk sebatian fenolik, 42.86 mg/g, 36.37 mg/g, 2.82 mg/g untuk asiaticoside and 18.66 mg/g, 15.87 mg/g, 3.75 mg/g untuk madecassoside). Ketiga-tiga ekstrak menunjukkan aktiviti antioksidan sederhana berbanding kawalan positif. Kesemua ekstrak, asiaticoside dan madecassoside merencat COX-1 dan COX-2 dan menyekat penghasilan PGE2 -aruhan TPA. Ekstrak etanol dan metanol merupakan perencat COX yang lebih kuat dan lebih poten daripada ekstrak akues. Oleh itu, walaupun ekstrak akues menunjukkan kebolehan antioksidan yang lebih tinggi, dari segi aktiviti anti-radang, pelarut hidrofobik iaitu etanol dan metanol ternyata lebih baik untuk mengekstrak Centella asiatica.
    Matched MeSH terms: Cyclooxygenase 1
  19. Saadawi S, Jalil J, Jasamai M, Jantan I
    Molecules, 2012;17(5):4824-35.
    PMID: 22538486 DOI: 10.3390/molecules17054824
    Acetylmelodorinol, chrysin and polycarpol, together with benzoic acid, benzoquinone and stigmasterol were isolated from the leaves of Mitrella kentii (Bl.) Miq. The compounds were evaluated for their ability to inhibit prostaglandin E₂ (PGE₂) and thromboxane B₂ (TXB₂) production in human whole blood using a radioimmunoassay technique. Their inhibitory effect on platelet activating factor (PAF) receptor binding to rabbit platelet was determined using ³H-PAF as a ligand. Among the compounds tested, chrysin showed a strong dose-dependent inhibitory activity on PGE(2) production (IC₅₀ value of 25.5 µM), which might be due to direct inhibition of cyclooxygenase-2 (COX-2) enzymatic activity. Polycarpol, acetylmelodorinol and stigmasterol exhibited significant and concentration-dependent inhibitory effects on TXB₂ production with IC₅₀ values of 15.6, 19.1 and 19.4 µM, respectively, suggesting that they strongly inhibited COX-1 activity. Polycarpol and acetylmelodorinol showed strong dose-dependent inhibitory effects on PAF receptor binding with IC₅₀ values of 24.3 and 24.5 µM, respectively.
    Matched MeSH terms: Cyclooxygenase 1/metabolism
  20. Siddiqui R, Lakhundi S, Iqbal J, Khan NA
    Exp Parasitol, 2016 Jul 2;168:45-50.
    PMID: 27381503 DOI: 10.1016/j.exppara.2016.06.011
    Non-steroidal anti-inflammatory drug, Diclofenac, targeting COX have shown promise in the treatment of Acanthamoeba keratitis, but the underlying mechanisms remain unknown. Using various NSAIDs, Diclofenac sodium, Indomethacin, and Acetaminophen, here we determined the effects of NSAIDs on the biological properties of Acanthamoeba castellanii belonging to the T4 genotype. Using amoebicidal assays, the results revealed that Diclofenac sodium, and Indomethacin affected growth of A. castellanii. In contrast, none of the compounds tested had any effect on the viability of A. castellanii. Importantly, all NSAIDs tested abolished A. castellanii encystation. This is a significant finding as the ability of amoebae to transform into the dormant cyst form presents a significant challenge in the successful treatment of infection. The NSAIDs inhibit production of cyclo-oxegenase, which regulates the synthesis of prostaglandins suggesting that cyclooxygenases (COX-1 and COX-2) and prostaglandins play significant role(s) in Acanthamoeba biology. As NSAIDs are routinely used in the clinical practice, these findings may help design improved preventative strategies and/or of therapeutic value to improve prognosis, when used in combination with other anti-amoebic drugs.
    Matched MeSH terms: Cyclooxygenase 1
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