2,3-Dibromo-1-[4-(2,3-dibromo-4,5-di­meth­oxy­benz­yl)-2,5-dimeth­oxy­benz­yl]-4,5-dimeth­oxy­benzene

The mol­ecule of the title compound, C26H26Br4O6, is located around a crystallographic inversion center. The dihedral angle between the central benzene ring and the outer benzene ring is 89.26 (1)°

Inhibition of human carbonic anhydrase isozymes I, II and VI with a series of bisphenol, methoxy and bromophenol compounds

Carbonic anhydrase inhibitors (CAI) are valuable molecules as they have several therapeutic applications, including anti-glaucoma activity. In this study, inhibition of three human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I, II and VI with a series of bisphenol and bromophenol derivatives was investigated. Molecular docking studies of a set of such inhibitors within CA I and II were also performed. K-I values of the molecules 2-9 were in the range of 10.025-892.109 mu M for hCA I, 1.437-59.107 mu M for hCA II and 11.143-919.182 mu M for hCA VI, respectively. Reported inhibitory activities of molecules 2-9 will assist in better understanding of structure-activity relationship studies of CAI.This study was financed by Turkish Republic Prime Ministry State Planning Organization (DPT), (project no: 2010K120440) and Agri Ibrahim Cecen University Scientific Research Council, (project no: Agri BAP-2010/K-10) for (MS) and by the Scientific and Technological Research Council of Turkey (TUBITAK, Grant No: TBAG-107T/348) for (SG, HTB and AM)

Synthesis and carbonic anhydrase inhibitory properties of novel bromophenols including natural products

(2-Bromo-3,4-dimethoxyphenyl) (3,4-dimethoxyphenyl) methanone (10) and its derivatives with Br, one dibromide and isomeric three tribromides, were synthesized. Demethylation of these compounds afforded a series of new bromophenols. Inhibition of human cytosolic carbonic anhydrase II (hCA II) isozyme by these new bromophenols and naturally occurring 3,4,6-tribromo-5-(2,5-dibromo-3,4-dihydroxybenzyl) benzene-1,2-diol (3), and 5,5'-methylenebis(3,4,6-tribromo-benzene-1,2-diol) (4) was investigated. The synthesized compounds showed carbonic anhydrase inhibitory capacities with IC50 values in the range of 0.7-372 mu M against hCA II. Some bromophenols investigated here showed effective hCA II inhibitory activity and might be used as leads for generating novel carbonic anhydrase inhibitors which are valuable drug candidates for the treatment of glaucoma, epilepsy, gastric and duodenal ulcers, neurological disorders, or osteoporosis

The effects of taxifolin on neuropathy related with hyperglycemia and neuropathic pain in rats: A biochemical and histopathological evaluation

Background. Hyperglycemia can be considered a determining factor in the development of diabetic neuropathy as well as neuropathic pain. There is a relationship between the excessive production of reactive oxygen species (ROS) and the pathogenesis of diabetic neuropathic pain. Taxifolin, on the other hand, is a flavonoid that has been documented to inhibit ROS production. Objectives. To investigate the effects of taxifolin, which has antioxidant and neuroprotective effects, on alloxan-induced hyperglycemia-induced neuropathy and neuropathic pain, biochemically and histopathologically. Materials and methods. The albino Wistar male rats were divided into 3 groups: Healthy group (HG), only alloxan group (AXG) and alloxan+taxifolin group (ATG). Hyperglycemia in animals was caused through intraperitoneal injection of alloxan at a dose of 120 mg/kg. Paw pain thresholds of animals were measured using Basile algesimeter. Sciatic nerve tissues were examined biochemically and histopathologically in order to evaluate neuropathy. Results. Our experimental results revealed that taxifolin significantly prevented the increase of plasma glucose concentration level with alloxan administration, the decrease of the paw pain threshold related to hyperglycemia, the change of oxidant-antioxidant balance in the sciatic nerve tissue in favor of oxidants, and the deterioration of tissue morphology in animals. Conclusions. Our experimental results indicate that taxifolin alleviates alloxan-induced hyperglycemia-related neuropathy and neuropathic pain

Effect of taxifolin on methotrexate-induced oxidative and inflammatory oral mucositis in rats: biochemical and histopathological evaluation

The role of oxidative stress, as well as inflammation in the pathogenesis of methotrexate (MTX)-induced oral mucositis, is a known fact. The anti-inflammatory, antitumor, antimicrobial, and antioxidant properties of taxifolin—the effect we tested against MTX-induced oral mucosal damage—are well known. Objective: Evaluating biochemically and histopathologically the effects of taxifolin on methotrexate-induced oral mucosal damage in rats. Methodology: In the taxifolin+MTX (TMTX) group, 50 mg/kg taxifolin was orally administered to rats by gavage. In the MTX and healthy (HG) groups, normal saline was applied to rats as solvent by the same method. One hour after administration of taxifolin and solvent, 5 mg/kg MTX was orally administered to rats in the MTX and TMTX groups. Taxifolin and methotrexate were administered once a day for 30 days. Macroscopic, biochemical, and histopathological evaluations were performed on the inner cheek and tongue tissues of rats. These parts were removed after rats were killed with a high-dose anesthesia. Results: Taxifolin with MTX prevented the increase in oxidant and pro-inflammatory parameters, such as malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), on the inner cheek and tongue tissues of rats. Moreover, taxifolin antagonized the decrease in total glutathione (tGSH). Taxifolin decreased MTX-induced histopathological damage. Conclusion: These findings suggest that taxifolin may be useful to treat MTX-associated oral mucositis

Protective effect of resveratrol against methotrexate-induced oxidative stress in the small intestinal tissues of rats

Kurt, Nezahat/0000-0002-1685-5332; Arslan, Aynur/0000-0001-5968-5823WOS: 000361557500026PubMed: 26379839The effect of resveratrol on the damage induced by methotrexate (MTX) in rat duodenum and jejunum tissue was investigated and evaluated in comparison with famotidine. the rats were divided into four groups as healthy group (HG), resveratrol+MTX (RMTX) group, famotidine+MTX (FMTX) group and the control group which received MTX (MTXC). RMTX group was given resveratrol 25 mg/kg and FMTX group famotidin 25 mg/kg, while MTXC and HG groups were orally administered distilled water once a day for 30 days. the rats in RMTX, FMTX and MTXC groups were given MTX of 5 mg/kg dose by the same way for 30 days. At the end of this period, amount of MDA, 8-OH/Gua and tGSH, and MPO gene expression were measured in the duodenal and jejunal tissues and the results were histopathologically evaluated. Resveratrol and famotidine were found to significantly prevent elevation of the MDA, 8-OH/Gua and MPO parameters with MTX and decrease of the levels of tGSH in the duodenal and jejunal tissues. Both drugs prevented severe damage to the villus and crypt epithelium in the duodenum and jejunum, congestion and hemorrhage, inflammatory cell infiltration and necrosis in the mucosa and submucosa due to MTX administration. Resveratrol could be considered in the clinical practice for treatment of the tissue damage in the intestines due to use of MTX, in comparison with famotidine. Resveratrol may be more advantageous than famotidine in long-term use against MTX toxicity since it does not inhibit gastric acid secretion

Moklobemidin Sıçanlarda Antiülser ve Antioksidan Aktivitesinin Araştırılması

Amaç: Peptik ülser tedavisinde kullanılan çok sayıda klasik antiülser ilaç grupları bulunsa da, bu ilaçlar ile ülserin kalıcı tedavisi sağlanamamaktadır. 1950'den beri antidepresan ilaçlar non - psikiyatrik bazı hastalıkların tedavisinde kullanılmaktadırlar. Birçok antidepresan ilacın antiülser aktiviteye sahip oldukları deneysel ve klinik çalışmalarla da gösterilmiştir. Moklobemid, monoaminooksidaz - A (MAO - A) enziminin selektif inhibitörü antidepresan bir ilaçtır. Klasik MAO inhibitörleri ile karşılaştırıldığında, etkinliğinin fazla olması ve yan etkilerinin az olması nedeni ile depresyon tedavisinde tercih edilmektedir. Bu çalışmada sıçan mide dokusunda moklobemidin antiülser etkilerinin araştırılması ve oksidan mekanizmalarla ilişkisinin belirlenmesi amaçlanmıştır. Gereç ve Yöntem: 10, 20, 40, 80 ve 150 mg/kg dozlarında kullanılan moklobemid ve 20 mg/kg dozunda kullanılan famotidinin antiülser aktivitesi sıçanlarda indometazin ile indüklenen ülser modelinde incelenmiş ve sonuçlar kontrol grubu ile karşılaştırılmıştır. Bulgular: Moklobemid kullanılan tüm dozlarda indometazin ülserlerinin oluşumunu anlamlı olarak azalttı. Moklobemid, kullanılan bu dozlarda sıçan mide dokusunda glutatyon (GSH), nitrik oksid (NO) seviyeleri ve süperoksid dismutaz (SOD) aktivitesini kontrol grubuna göre artırırken; malondialdehid (MDA) seviyesi ve myeloperoksidaz (MPO) aktivitesini ise azaltmıştır. Sonuç: Antidepresan bir ilaç olan moklobemidin, güçlü bir antiülser ajan olduğu tespit edilmiştir. Moklobemidin antiülser etki mekanizmasında toksik oksidan radikallerin baskılanması ve antioksidan mekanizmaların aktivasyonu rol oynamaktadır.Objective: Even though there are many drugs for the treatment of gastric ulcers, these drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been used for several non-psychiatric indications. Many antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. Moclobemide is an antidepressant drug which inhibits monoamine oxidase-A (MAO) enzyme selectively. When it is compared to the classic antidepressants drugs, moclobemide is the first choice in depression treatment because of its effectiveness and less side effects. This study aimed to investigate the antiulcer effects of moclobemide and to determine its relationship with antioxidant mechanisms in rat gastric tissue. Materials and Methods: The antiulcer activities of 10, 20, 40, 80, 150 mg/kg moclobemide and 20 mg/kg famotidine have been investigated on indomethacin-induced ulcers in rats, and the results have been compared with that of the control group. Results: Moclobemide decreased the indomethacin-induced ulcers significantly at all doses used. While used doses of moclobemide increased the glutathione (GSH), nitric oxide (NO) level and superoxide dismutase (SOD) activity, it decreased the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in stomach tissue when compared to the control group.Conclusion: It is determined that an antidepressant drug, moclobemide is a potent anti-ulcer agent. Inhibition of toxic oxidant radicals and activation of antioxidant mechanisms play a role in its antiulcer effect mechanisms

Acute and chronic antiinflammatory effects of Hedera colchica in rats

Hedera helix and Hedera colchica are the members of Araliaceae family. In the present study, we tested the possible antiinflammatory effects of crude (CSE) and purified (SPE) extracts of Hedera colchica in carrageenan- and cotton pellet-induced acute and chronic inflammation models in rats. Both CSE and SPE of Hedera colchica were found to have antiinflammatory effects. The most potent drug was found as indomethacin (90%) in the 4 h measurements, while SPE (83%) and CSE (55%) of Hedera colchica in 100 mg/kg doses were found to have quite potent effects in acute phase of inflammation, in respect to control values. For testing chronic antiinflammatory (antiproliferative) effects, cotton pellet granuloma test was conducted. SPE was found as the most potent drug in chronic phase of inflammation with an effect of 64.32%. Indomethacin was found more potent than the CSE of Hedera colchica, and potency was found as 61.2 and 58%, respectively