Evaluation of Cardioprotective Effect of 3,5,3′-Tri-iodo-L-thyronine in Isoproterenol-Induced Cardiotoxicity

T3 (3,5,3′-triiodothyronine) has drawn relatively little attention in relation to cardiovascular (CVS) diseases. The present study was designed to evaluate the cardioprotective action of T3 in isoproterenol-(ISO-) induced cardiac toxicity. Female Wistar rats were exposed with ISO (100 mg/kg, body weight, subcutaneously) for 2 days at the interval of 24 h followed by T3 (3 μg/kg, body weight, orally) treatment for 3 days. Positive control rats received only ISO (100 mg/kg, body weight, subcutaneously) for 2 days at the interval of 24 hrs. Control group animals received normal saline as a vehicle. As expected, ISO-induced significant changes were observed in low-density lipoprotein, total cholesterol, ALT, CK-MB to TCK ratio, and prolongation of QT interval in electrocardiogram, which is toward normalization after T3 treatment. Lower heart weight, upregulation of cardiac myosin heavy chain alpha (MHC-α), and reduced inflammatory cell infiltration, myonecrosis, vacuolar changes, and a trend toward normal cardiac muscle fiber architecture in microscopic examination of cardiac tissue further support the cardioprotective effect of T3

<span style="font-size:19.5pt;mso-bidi-font-size:14.5pt; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA">Synthesis of benzimidazo[1<i><span style="font-size:20.0pt;mso-bidi-font-size: 15.0pt;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA">,</span></i><span style="font-size:20.0pt;mso-bidi-font-size:15.0pt;font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:AR-SA;mso-bidi-font-style:italic">2<i>-c </i><span style="font-size:19.5pt;mso-bidi-font-size:14.5pt;font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:AR-SA">]quinazolines as possible bronchodilators^†</span></span></span>

434-439<span style="font-size:13.5pt;mso-bidi-font-size:8.5pt; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">Synthesis of some 6-aryl-benzimidazo[1,2-c]quinazolines 4 have been critically investigated. The first method, based on the condensation of substituted- 1,3-benzoxazin-4-(3H)-one <b style="mso-bidi-font-weight: normal">2 with o-phenylenediamine followed by cyclization of the resulting 2-aryl-3-(2-aminophenyl) quinazolin-4(3H)one 3 by direct heating. A second (and new) method, based on dehydrocyclization of 2 with <i style="mso-bidi-font-style: normal">o-phenylenediamine in the presence of polyphosphoric acid provides a wide variety of the 6- arylbenzimidazo[1 ,2-<i style="mso-bidi-font-style: normal">c]quinazolines, usually in high yield. A third synthesis providing low yield involves dehydrocyclization of 2 with o-phenylenediamine by direct heating above its melting point. The structure of the compounds 4 have been established on the basis of their elemental analyses and spectral (IR, 1H NMR and mass) data. The bronchodilatory activity of compounds <b style="mso-bidi-font-weight: normal"><span style="font-size:14.0pt;mso-bidi-font-size:9.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">4a <span style="font-size:13.5pt; mso-bidi-font-size:8.5pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">and 4b<span style="font-size:14.0pt; mso-bidi-font-size:9.0pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"=""> <span style="font-size:13.5pt;mso-bidi-font-size: 8.5pt;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">is reported using in vitro and in vivo animals models.</span

New antihistaminic agents : Part 6-Synthesis and H₁ -antihistaminic evaluation of 3-[(N,N -dialkylamino )alkyl]-6-halo-2-phenyl-3,4-dihydroquinazolin-4(3H)-ones^†

813-816Eight new 3-(N,N-dialkylamino)alkyl derivatives of 2-phenyl-3,4-dihydroquinazolin-4(3H)-ones 3a-h have been synthesized as antihistaminic agents. They have been characterized by elemental analyses and spectral (IR, 1H NMR and mass) data. The in vitro and in vivo H1-antihistaminic potencies of 3a-h have been evaluated by isolated guinea pig ileum method and histamine chamber method respectively. Among the compounds tested compound 3d is found to be the most potent with the percentage protection (in vivo) 74.77% and IC50 (in vitro) 1.3×10-3 g/L

Coagonist of GLP-1 and glucagon receptors ameliorates non-alcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is often associated with obesity and type 2 diabetes. Coagonist of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) are under clinical investigation for the treatment of obesity and type 2 diabetes. In this study, we have demonstrated the effect of a balanced coagonist in the treatment of NAFLD using mice models. GLP-1R agonist exendin-4, glucagon, and coagonist (Aib2 C24 Chimera2) were administered to C57BL6/J mice, in which NAFLD was induced by carbon tetrachloride (CCl4) treatment after in high fat diet (HFD) feeding, and CDAHFD (choline-deficient, L-amino acid-defined, HFD). Repeated dose administration of coagonist significantly attenuated liver inflammation and steatosis induced by acute and long-term treatment with CCl4 in HFD-fed mice. Coagonist markedly attenuated the CDAHFD-induced expression of TIMP-1, MMP-9, TNF-Îą, MCP-1, COL1A1 and Îą-SMA. It also inhibited progression of hepatic steatosis and fibrosis in mice. Exendin-4 was better than glucagon, but coagonist was most effective in reduction of hepatic inflammation as well as steatosis. Coagonist of GLP-1R and GCGR improved NAFLD in C57BL6/J mice. This effect is mediated by reduction in lipotoxicity and inflammation in liver.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

An Efficient and Scalable Synthesis of <i>tert</i>-Butyl (3a<i>R</i>,6a<i>S</i>)‑5-Oxohexa­hydrocyclo­ penta­[<i>c</i>]­pyrrole-2(1<i>H</i>)‑carboxylate: A Pharmacologically Important Intermediate

Hexahydro­cyclo­penta­pyrrolone derivatives constitute an important class of bicycles, and it represents an essential pharmacophore for diversified pharmacological activities. A highly efficient process for the synthesis of <i>tert</i>-butyl­(3a<i>R</i>,6a<i>S</i>)-5-oxohexa­hydro­cyclo­penta­[<i>c</i>]­pyrrole-2­(1<i>H</i>)-carboxylate <b>1</b> has been developed. The improved process involves transformation of isoindole <b>4</b> to diacid <b>5</b>, using an inexpensive KMnO₄ mediated oxidative cleavage as a key step. The developed process was cost-effective, high yielding, kilogram scalable, and commercially viable for synthesis of <b>1</b>