Effect of a novel succinamic acid derivative as potential anti-diabetic agent in experimental diabetic rats

4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid which is a succinamic acid derivative has been synthesized in 3 step reaction with malic acid. Its structure confirmation was done by various techniques like 1H NMR, 13C NMR, & HRMS and is recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. In the present study, the effect of 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid on plasma glucose, serum insulin, serum lipid profile and lipid peroxidation in streptozotocin–nicotinamide induced type 2 diabetic model was investigated.  4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid was administered orally (20 mg/kg b.w.) to streptozotocin + nicotinamide (STZ + NAD) induced diabetic rats for 28 days. A significant increase in fasting blood glucose levels, HbA1c levels, Serum lipid profile (TG & TC) and in  the levels of Malonaldialdehyde (MDA, end product of lipid peroxidation) was observed in STZ +NAD diabetic rats whereas the levels of high density lipoprotein-cholesterol (HDL-C) and serum insulin levels were significantly decreased  in STZ + NAD induced diabetic rats The effect of 4-((benzyloxy)amino)-2-hydroxy-4-oxobutanoic acid was compared with glibenclamide, a reference drug. Treatment with 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid and glibenclamide resulted in a significant reduction of fasting blood glucose levels with increase in plasma insulin levels in diabetic treated rats. 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid also resulted in a significant improvement in serum lipids and lipid peroxidation products. Our results suggest the potential role of 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid in the management of type-2 diabetes mellitus experimental rats. Keywords: 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid, dyslipidemia, streptozotocin induced diabetes, lipid peroxidatio

Regulation of Gene Expression and Inhibition of Experimental Prostate Cancer Bone Metastasis by Dietary Genistein

AbstractProstate cancer frequently metastasizes to the bone, and the treatment outcome for metastatic prostate cancer has been disappointing so far. Dietary genistein, derived primarily from soy product, has been proposed to be partly responsible for the low rate of prostate cancer in Asians. Our previous studies have shown that genistein elicits pleiotropic effects on prostate cancer cells, but there are no studies documenting comprehensive gene expression profiles and antitumor effects of dietary genistein on human prostate cancer grown in human bone environment. In this study, we investigated the effects of genistein on PC3 prostate cancer cells and experimental PC3 bone tumors created by injecting PC3 cells into human bone fragments previously implanted in severe combined immunodeficient (SCID) mice (SCID human model). We found that genistein significantly inhibited PC3 bone tumor growth using both prevention and intervention strategies. By using microarray and real-time polymerase chain reaction technology, we found that genistein regulated the expression of multiple genes involved in the control of cell growth, apoptosis, and metastasis both in vitro and in vivo. For example, the expression of various metalloproteinases (MMPs) in PC3 bone tumors was inhibited by genistein treatment, whereas osteoprotegerin was upregulated. MMP immunostaining and transfection experiments also demonstrated that MMP-9 expression was inhibited in PC3 cells in vitro and PC3 bone tumors in vivo after genistein treatment. These results, particularly the in vivo results, demonstrate that dietary genistein may inhibit prostate cancer bone metastasis by regulating metastasis-related genes. Genistein may thus be a promising agent for the prevention and/or treatment of prostate cancer

Synthesis of Some Salicylaldehyde-Based Schiff Bases in Aqueous Media

A new efficient and environmental friendly procedure for the synthesis of a series of salicylaldehyde-based schiff bases under microwave irradiation is described. The method is compared with the conventional method also. The present work involves condensation of salicylaldehyde with various aromatic amines in water under microwave irradiation. A judicious choice of the solvent and reaction conditions allowed the final products to be generated in excellent yields in a one-step procedure, whereas experiments under thermal conditions led to lower yields with tedious work-up. Microwave irradiation method gives advantages like reduction in reaction time, increase in conversion, reduced wastes, and good yields. The structures of synthesized compounds were confirmed by IR, 1HNMR, and Mass Spectra data

<span style="color:black;mso-bidi-language:HI">One pot facile synthesis of 5-alkyl-1,2-dihydro-spiro[4<i>H</i>-3, 1-benzoxazine<span style="color:#030303;mso-bidi-language:HI">- <span style="color:black;mso-bidi-language:HI">2<span style="color:#030303; mso-bidi-language:HI">,<span style="color:black;mso-bidi-language:HI">3'[3<i>H</i>]indol]-4,2'-diones under microwave irradiation </span></span></span></span></span>

1504-1510A fa<span style="color:#030303; mso-bidi-language:HI">cile sy<span style="color:black; mso-bidi-language:HI">nth<span style="color:#030303;mso-bidi-language: HI">esis of some n<span style="color:#030303; mso-bidi-language:HI">ove<span style="color:black;mso-bidi-language: HI">l 5-al<span style="color:#030303; mso-bidi-language:HI">kyl-1,2-d<span style="color:black; mso-bidi-language:HI">ih<span style="color:#030303;mso-bidi-language: HI">ydro-s<span style="color:black; mso-bidi-language:HI">pir<span style="color:#030303;mso-bidi-language: HI">o[4H-3, 1-<span style="color:#030303; mso-bidi-language:HI">benzoxa<span style="color:black; mso-bidi-language:HI">zin<span style="color:#030303;mso-bidi-language: HI">e-2,<span style="color:black; mso-bidi-language:HI">3<span style="color:#030303;mso-bidi-language: HI">'[3H]ind<span style="color:#030303; mso-bidi-language:HI">ol]-4<span style="color:#303030; mso-bidi-language:HI">,<span style="color:#030303;mso-bidi-language: HI">2'-dio<span style="color:black; mso-bidi-language:HI">ne<span style="color:#030303;mso-bidi-language: HI">s, in <span style="color:#030303; mso-bidi-language:HI">hig<span style="color:black; mso-bidi-language:HI">h <span style="color:#030303;mso-bidi-language: HI">yiel<span style="color:black; mso-bidi-language:HI">d<span style="color:#030303;mso-bidi-language: HI">s, has bee<span style="color: black;mso-bidi-language:HI">n <span style="color:#030303;mso-bidi-language: HI">carried o<span style="color:black; mso-bidi-language:HI">u<span style="color:#030303;mso-bidi-language: HI">t cl<span style="color:#030303; mso-bidi-language:HI">assica<span style="color:black;mso-bidi-language: HI">lly as well <span style="color:#030303; mso-bidi-language:HI">as <span style="color:black;mso-bidi-language: HI">under m<span style="color:#030303; mso-bidi-language:HI">icrowave ir<span style="color:#030303; mso-bidi-language:HI">radiat<span style="color:black; mso-bidi-language:HI">i<span style="color:#030303;mso-bidi-language: HI">on in so<span style="color:black; mso-bidi-language:HI">l<span style="color:#030303;mso-bidi-language: HI">vent fr<span style="color:black; mso-bidi-language:HI">e<span style="color:#030303;mso-bidi-language: HI">e conditio<span style="color:black; mso-bidi-language:HI">n<span style="color:#030303;mso-bidi-language: HI">s. Microwave ir<span style="color:#030303; mso-bidi-language:HI">radiation offer<span style="color:#030303; mso-bidi-language:HI">s tre<span style="color:black;mso-bidi-language: HI">men<span style="color:#030303; mso-bidi-language:HI">dous adva<span style="color: black;mso-bidi-language:HI">nt<span style="color:#030303;mso-bidi-language: HI">ages in t<span style="color:black; mso-bidi-language:HI">h<span style="color:#030303;mso-bidi-language: HI">e form of s<span style="color:black; mso-bidi-language:HI">h<span style="color:#030303;mso-bidi-language: HI">ort<span style="color:black; mso-bidi-language:HI">er <span style="color:#030303;mso-bidi-language: HI">reactio<span style="color:black; mso-bidi-language:HI">n t<span style="color:#030303;mso-bidi-language: HI">ime<span style="color:#303030; mso-bidi-language:HI">, <span style="color:#030303;mso-bidi-language: HI">opera<span style="color:black; mso-bidi-language:HI">ti<span style="color:#030303;mso-bidi-language: HI">onal s<span style="color:black; mso-bidi-language:HI">im<span style="color:#030303;mso-bidi-language: HI">plic<span style="color:black; mso-bidi-language:HI">it<span style="color:#030303;mso-bidi-language: HI">y, cl<span style="color:#030303; mso-bidi-language:HI">eane<span style="color:black; mso-bidi-language:HI">r <span style="color:#030303;mso-bidi-language: HI">reactio<span style="color:black; mso-bidi-language:HI">n<span style="color:#030303;mso-bidi-language: HI">, easy work-up a<span style="color:black; mso-bidi-language:HI">nd bett<span style="color:#030303;mso-bidi-language: HI">er yields <span style="color:black; mso-bidi-language:HI">as c<span style="color:#030303;mso-bidi-language: HI">ompared <span style="color:black; mso-bidi-language:HI">to th<span style="color:#030303;mso-bidi-language: HI">e classica<span style="color:black; mso-bidi-language:HI">l me<span style="color:#030303;mso-bidi-language: HI">tho<span style="color:black; mso-bidi-language:HI">d. B<span style="color:#030303;mso-bidi-language: HI">esides this<span style="color:black; mso-bidi-language:HI">, som<span style="color:#030303;mso-bidi-language: HI">e nove<span style="color:black; mso-bidi-language:HI">l 6-alk<span style="color:#030303;mso-bidi-language: HI">yla<span style="color:black; mso-bidi-language:HI">nthr<span style="color:#030303;mso-bidi-language: HI">anilic ac<span style="color:black; mso-bidi-language:HI">ids r<span style="color:#030303;mso-bidi-language: HI">equired fo<span style="color:black; mso-bidi-language:HI">r th<span style="color:#030303;mso-bidi-language: HI">e synthes<span style="color:black; mso-bidi-language:HI">is of new spiro compounds have also been synthesized. The importance of alkyl substituent at C-6 position in anthranilic acid has been recognized again in such a cyclocondensation reaction, even when it is carried out under microwave irradiation. This is also supported by molecular modeling. </span

Nanoparticles of oxidized-cellulose synthesized by green method

Site specific drug delivery is the foremost requisite for chemotherapy to avoid the associated side effects. For this, stimuli-responsiveness of the drug delivery device is of great interest to selectively release the loaded drug to the tumor cells. Herein, the oxidized cellulose nanoparticles (OCNPs) were synthesized by oxidation of cellulose with 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) and sodium periodate followed by sonication. Doxorubicin (Dox), as model anticancer drug, was loaded on the synthesized OCNPs via pH-responsive linkages between functional groups of Dox and OCNPs. Its release behaviour was studied in medium of different pH values. Dox release was maximum at pH 5.0 and pH 6.8 i.e., endosomal and extracellular pH, respectively in tumor tissue, and minimum at physiological pH 7.4 of normal tissues. Various mathematical models were applied to elucidate the release mechanism of the Dox from the loaded OCNPs. Dox release followed non-Fickian diffusion mechanism. The results suggest that these pH-responsive OCNPs are effective and promising Dox-delivery carriers for cancer treatment and capable of reducing side-effects of this anticancer drug to the normal cells. Keywords: Green synthesis, Oxidized-cellulose nanoparticles, Site specific drug delivery, Non-Fickian diffusio

One pot synthesis of novel 1, 2-dihydro-5-methyl-spiro[4<i>H</i>-3,1-benzoxazine-2,3'[3<i>H</i>]indol]-4,2'-diones

2381-2385A facile one pot synthesis of some novel spiro heterocycles such as 5-methyl-spiro [benzoxazine-indol]-4,2'-diones 3a-j is carried out by cyclocondensation of indole-2,3-diones 1a-j with 6-methylanthranilic acid 2 in ethanol under dry condition. The importance of substituent at C-6 position in 2 has been highlighted in such condensation reactions. The molecular modelling has shown that such substitution perfectly aligns the carboxyl group for intramolecular cyclization to take place. The reaction is of great value because of its environmentally benign character as non-toxic chemicals are used and no waste is generated

Fluorescent microscopy and Ziehl-Neelsen staining of bronchoalveolar lavage, bronchial washings, bronchoscopic brushing and post bronchoscopic sputum along with cytological examination in cases of suspected tuberculosis

Objectives: Ever since the discovery of Mycobacterium tuberculosis in 1882, many diagnostic methods have been developed. However "The gold standard" for the diagnosis of tuberculosis (TB) is still the demonstration of acid fast Bacilli (AFB) by microscopic examination of smear or bacteriological confirmation by culture method. Materials and Methods: In suspected 75 patients with active pulmonary TB, the materials obtained bronchoscopically, were bronchoalveolar lavage (BAL), bronchial brushings, bronchial washings and post bronchoscopic sputum. Four smears were made from each of the specimen. Fluorescent Staining, Ziehl–Neelsen (ZN), Pap and May Grunwald-Giemsa (MGG) stains were carried out for cytological examination. Results: Fluorescent stain yielded maximum AFB positivity in all the methods, that is 36 (48%) in post fibre-optic bronchoscopy (FOB) sputum and 19 (25.33%) by fluorescence microscopy in both bronchial brushings and bronchial washings. Maximum yield of AFB with ZN staining 12 (16%) was equal to the post FOB sputum and bronchial brushings samples. It was followed by 6 cases (8%) in BAL and 4 (5.3%) in bronchial washings. The cytological examination was suggestive of TB in only 8 (10.66%) cases in bronchial washings and 6 (8%) cases in post FOB collection. It was equal in BAL and Bronchial brushings each that is 5 (6.67%). Conclusion: Bronchoscopy is a useful diagnostic tool and fluorescent microscopy is more sensitive than ZN and cytology. On X-ray examination, other diseases like malignancy or fungus can also mimick TB. So apart from ZN staining or fluorescence microscopy, Pap and MGG stain will be worthwhile to identify other microorganisms

Synthesis and antibacterial/antitubercular activity evaluation of symmetrical <i style="mso-bidi-font-style:normal">trans</i>-cyclohexane-1,4-diamine derivatives

1441-1450<span style="font-size:12.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-gb;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="" lang="EN-GB">A library of symmetrical trans-cyclohexane-1,4-diamine derivatives have been synthesized and evaluated for their activity against the M. tb H37Rv strain. Most of the synthesized compounds show moderate to weak activity against M. tb H37Rv strain. Out of twenty-seven compounds tested, four compounds having substitution at p-position on the aromatic ring exhibit activity with MIC99 value ranging from 12.5 - 25 µM. Compound 9u having i-propyl group substitution at p-position is found to be the most potent among all the tested compounds with MIC99 value of 12.5 µM against M. tb H37Rv strain. All these compounds have also been tested against <i style="mso-bidi-font-style: normal">Methicilin resistant Staphylococcus aureus (MRSA), and four of the compounds <b style="mso-bidi-font-weight: normal">9c, 9i, 9p and 9s possess good antibacterial activity with IC50 ranging from 128 mg/L – 256 mg/L.</span

Bone Microenvironment Modulates Expression and Activity of Cathepsin B in Prostate Cancer

Prostate cancers metastasize to bone leading to osteolysis. Here we assessed proteolysis of DQ-collagen I (a bone matrix protein) and, for comparison, DQ-collagen IV, by living human prostate carcinoma cells in vitro. Both collagens were degraded, and this degradation was reduced by inhibitors of matrix metallo, serine, and cysteine proteases. Because secretion of the cysteine protease cathepsin B is increased in human breast fibroblasts grown on collagen I gels, we analyzed cathepsin B levels and secretion in prostate cells grown on collagen I gels. Levels and secretion were increased only in DU145 cells—cells that expressed the highest baseline levels of cathepsin B. Secretion of cathepsin B was also elevated in DU145 cells grown in vitro on human bone fragments. We further investigated the effect of the bone microenvironment on cathepsin B expression and activity in vivo in a SCID-human model of prostate bone metastasis. High levels of cathepsin B protein and activity were found in DU145, PC3, and LNCaP bone tumors, although the PC3 and LNCaP cells had exhibited low cathepsin B expression in vitro. Our results suggest that tumor-stromal interactions in the context of the bone microenvironment can modulate the expression of the cysteine protease cathepsin B