Accumulating evidence indicates the role of endocrine disruptor bisphenol A (BPA) in many pathological conditions. Histone deacetylase (HDAC) inhibition has potential for the treatment of many diseases/abnormalities. Using a mouse BPA exposure model, this study investigated the hepatoprotective effects of the Food and Drug Administration–approved HDAC2 inhibitor valproic acid (VPA) against BPA-induced liver pathology. We randomly divided 30 adult male Swiss albino mice (8 weeks old; N = 6) into five groups: group 1, no treatment (sham control (SC)); group 2, only oral sterile corn oil (vehicle control (VC)); group 3, 4 mg/kg/day of oral BPA (single dose (BPA group)); group 4, 0.4% oral VPA (VPA group); and group 5, oral BPA + VPA (BPA + VPA group). At the age of 10 weeks, the mice were euthanized for biochemical and histological examinations. BPA promoted a significant decrease in the body weight (BW), an increase in the liver weight, and a significant increase in the levels of liver damage markers aspartate aminotransferase and alanine aminotransferase in the BPA group compared to SC, as well as pathological changes in liver tissue. We also found an increase in the rate of apoptosis among hepatocytes. In addition, BPA significantly increased the levels of oxidative stress indices, malondialdehyde, and protein carbonylation but decreased the levels of reduced glutathione (GSH) in the BPA group compared to SC. In contrast, treatment with the HDAC2 inhibitor VPA significantly attenuated liver pathology, oxidative stress, and apoptosis and also enhanced GSH levels in VPA group and BPA + VPA group. The HDAC2 inhibitor VPA protects mice against BPA-induced liver pathology, likely by inhibiting oxidative stress and enhancing the levels of antioxidant-reduced GSH.
Mohamed A. Al-Griw, Zaynab Osama Alshibani, Rabia Omar abdullah Alghazeer, Mohamed Elhensheri, Refaat. M. Tabagh, Areej A. Eskandrani, Wafa S. Alansari, Mahmoud M. Habibulla, Ghalia Shamlan(6-2022)

Abstract The permittivities and dielectric losses of 2-Piperedone, -Caprolactam, 2-Azacyclooctanone and 2-Azacyclononanone have been studied in chloroform solutions. They have been measured using Q meter at frequency range 150KHz to 15MHz.Both 2-Piperedone and -Caprolactam solutions were studied at concentration range 0.05 to 0.25M and over temperatures range of -10 to 45 and. The dielectric studies of 2-Azacyclooctanone solutions cover a concentration range 0.05 to 0.125M and over temperature range of -10 to 45, while that of 2-Azacyclononanone solutions were studied at concentration range 0.01 to 0.075M and over temperature range of -10 to 45. The permittivities at higher concentrated solutions up to 1.5M of 2-Pipere-done, -Caprolactam and 2-Azacyclononanone were also measured at 2MHz using dipole meter DM01 over the temperature rang -10 to 45.The static permittivities for the four systems were discussed as the affect concentration, temperature and the number of CH2 group in the cyclic amides. All show normal behaviour except that the CH2 does not show clear affect. Single relaxation process were observed for the studied compound in the chloroform solutions ( =10-9 sec). All cases, the presence of a relaxation process was established at frequencies higher than used here. These relaxation processes were discussed in terms of their relation to concentration and the number of CH2 group. The dielectric activation energies were calculated using Eyring equation. The obtained values were discussed also in terms of concentration affect. A dependence of on concentration was observed. The dipole moments for the four studied compounds in solutions were evaluated using of Cole-Cole a semicircle plots, which considered to be associated with the relaxation process and other dipole moments were evaluated using =. This was assigned as an apparent dipole moment. All these dipole moments were discussed in terms of concentration and temperature affect. The obtained dipole moments in all studied case were much larger than those expected for planer dimers association. So they assigned to the presence of dimers and trimer or tetramers association in the studied solutions.Kirkwood correlation factor for the studied systems were calculated and discussed as a function of concentration. All values of g are less than unity and were assigned to a cyclic association form.
لطفية صادق حسن المجدوب (2010)

الهدف الأساسي من هذا المشروع هو تحضير بعض 4-ثيازوليدينونات مستبدلة وتطوير طريقة جديدة لتحضير مشتقات ثيوفين.قمنا بتحضير بعض مشتقات 4-ثيازوليدينونات معروفة وجديدة بتفاعل مركبات ميثيلين نشطة مختلفة (201a-g) مع فينيل أيزوثيوسيانات في دايكوسان في وجود مسحوق جاف من هيدروكسيد البوتاسيوم عند 0-5oC ومعالجة أملاح بوتاسيوم كيتين N، S-- أسيتال الناتجة (202a-g) مع إيثيل كلوروأسيتات ليعطي (203a-g) وقد استخدمت 4-ثيازوليدينونات المحضرة 203a-f)) كمواد بادئة لتفاعلات وتحولات أخرى. حضرت في هذه الدراسة مركبات جديدة (206a-c) بازدواج ملح الديأزونيوم لبارا تولويدين (205) مع 4-ثيازوليدينونات (203a,d,f) ليعطي مشتقات 5-ديازينيل-4- ثيازوليدينونات ((206a-c وقد تفاعلت مشتقات الثيازوليدينون (203a، b، d، f) مع ألدهيدات متنوعة (207a-c) وتم الحصول على مشتقات 5,2 –ثنائي أيليدين (208a-d). لقد جرى سابقا تحويل (203a) بنجاح إلى مشتقات ثيوفين إستر عند تفاعلها مع كحولات وثيوفين أميد عند تفاعلها مع الأمونيا. وكاستمرار لهذا تمت دراسة تفاعلات الكحولات مع 4-ثيازوليدينونات متنوعة لتحويلها إلى مشتقات ثيوفين-2-كربوكسيلات، فقد تفاعل مشتق ثنائي سيانو 4-ثيازوليدينون (203a) بنجاح مع كحول ايزوبيوتيل وأعطى 3-أمينو ثيوفين -2-كربوكسيلات (211a). ولكن هذا الكحول فشل في تحويل بقية 4-ثيازوليدينونات (203b-f). أما المركبين (203d، e) فقد تفاعلا مع الإيثانول بنجاح تحت مكثف راد في وجود ثلاثي إيثيل أمين كحفاز لتعطيا نفس الناتج (211b). وهذا له دلالات كبيرة في تحديد التشكل الهندسي للثيازوليدينون البادئ وميكانيكية التفاعل. ومن جهة أخرى تفاعل مركب (203f) مع الإيثانول تحت مكثف راد ليعطي ثيوفين -4,2-ثنائي كربوكسيلات (211c). كما أدت معالجة مركبات 4-ثيازوليدينونات (203b-c) بالأمونيا إلى تكوين مشتقات ثيوفين كربوكساميد (211a-b) بميكانيكية مشابهة وذات أهمية في تحديد التشكل الهندسي أيضا. ولقد أعطى تفاعل التكثيف لمركب (209a) مع ألدهيدات أروماتية مثل بنزالديهايد وبارا نيتروبنزالديهايد في وجود كبريتات الصوديوم اللامائية مشتقات أزوميثين (218a,b ) . أما ثيينوبيريميدينونات الجديدة (219a-d) فقد تم تحضيرها في هذه الدراسة بتفاعل مركب (209a) مع عدد من الألدهيدات الأروماتية تحت مكثف راد في حمض اسيتيك ثلجي. ومن جهة أخرى تحولق مركب الديازونيوم من (209a) وأعطى مشتقة ثيينو-ترايازينون(221) بدل من الأزيد المتوقع (222) وأخيرا أدى تفاعل 3-أمينوثيوفين-2-كربوكسيليت (210b) مع ثلاتي إيثيل أورثوفورميث إلى تكوين (223). Abstract The main goal of this research project i to synthesize some substituted 4-thiazolidinone and to develop new routes for synthesis of thiophene derivatives. We synthesized some known and novel 4-thiazolidinones by reacting different active methylene compounds (201a-g) with phenylisothio cyanate in dioxane in the presence of dried powder potassium hydroxide at 0-5oC , and treating the resulting ketene-N,S-acetals potassium salts (202a-g) with ethylchloro acetate to give (203a-g). The synthesized 4-thiazolidinones (203a-f) were used as starting materials for further reactions and transformations. In this study novel compounds (206a-c) were prepared by coupling diazonium salt of p-toulidine (205) with 4- thiazolidinone derivatives (203a, d, f), to give 5-diazenyl- 4-thiazolidinone derivatives (206a-c). Thiazolidinone derivatives (203a, b, d, and f) were reacted with a variety of aldehyds (207a-c), to give the corresponding 2, 5-diylidiene derivatives (208a-d). Conversion of 2-ylidene-3-phenyl- 4-thiazolidinones into thiophene-2-carboxylate derivatives was attempted. While compounds (203b-f) did not react with isobutyl alcohol, dicyano derivative (203a) was successfully transformed into 3-aminothiophene carboxylate (211a). Refluxing compounds (203d, e) in ethanol in the presence T.E.A as catalyst gave the same product (211b) .This result is significant in determining the geometry of the starting 4-thiazolidinone and in the mechanism of these transformations. On the other hand, compound (203f) on refluxing with ethanol afforded the thiophene-2, 4-dicarboxylate (211c). Treatment of compounds (203b-c) with ammonia afforded the thiophene carboxamide derivatives (211a-b), involving similar mechanism and significance in geometrical determination of the starting 4-thiazolidinones. The condensation reaction of compound (209a) with aromatic aldehydes in presence sodium sulfate gave the azomethine Schiff base derivatives (218a, b). Some of novel thienopyrimidinone (219a-d) have been synthesized in this work by refluxing compound (209a) with some aromatic aldehyde in glacial acetic acid On the other hand diazonium solution of compound (209a) cyclized into thieno triazinone derivative (221) rather than expected compound (222). The 3-amino thiophene- 2-carboxylate (210b) was refluxed with triethylortho formate to produce compound (223).
نسرين أبو غرارة محمد دويئة (2014)