Synthesis and Characterization of Macrocyclic Chiral Tröger's Base Phenhomazine Candidates as Anticancer Agent.

1,4,7,10-Tetraoxa[10](2,8)trögerophane 5 was synthesized from its corresponding precursors. Heating of 2 with p-nitrophenoxide afforded bis(p-nitrophenyl)ether 3, which was treated with hydrazine hydrate to give bis(p-aminophenyl)ether 4. Treatment of 4 with paraformaldehyde and triflouroacetic anhydride gave trögerophane 5. Reaction of 5 with trifluroacetic anhydride afforded phenhomazine derivative 6, which was treated with potassium carbonate to afford tetrahydrophenhomazine 7. Finally, reaction of 7 with phenacylchloride, bromoacetic acid, or ethyl bromoacetate in the presence of triethyl amine under reflux, afforded the corresponding macrocyclic compounds 8, 9 and 10, respectively. The synthesized trögerophane,precursors and its newly synthesized phenhomazines derivatives were screened for anticancer activity. Results revealed that 1,4,7,10-tetraoxa[10](2,8)trögerophane had a promising selectivity towards colon cancer cell line with an IC50 of 92.7 µg/ml.

In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates.

In this study, some of new thiophenyl thienopyrimidinone derivatives 2-15 were prepared and tested as anti-cancer agents by using thiophenyl thieno[2,3-d]pyrimidinone derivative 2 as a starting material, which was prepared from cyclization of ethyl ester derivative 1 with formamide. Treatment of 2 with ethyl- chloroacetate gave thienopyrimidinone N-ethylacetate 3, which was reacted with hydrazine hydrate or anthranilic acid to afford acetohydrazide 4 and benzo[d][1,3]oxazin-4-one 5, respectively. Condensation of 4 with aromatic aldehydes or phenylisothiocyanate yielded Schiff base derivatives 6,7, and thiosemicarbazise 10, which were treated with 2-mercaptoacetic acid or chloroacetic acid to give the corresponding thiazolidinones 8, 9, and phenylimino-thiazolidinone 11, respectively. Treatment of 4 with ethylacetoacetate or acetic acid/acetic anhydride gave pyrazole 12 and acetyl acetohydrazide 13 derivatives, respectively. The latter compound 13 was reacted with ethyl cycno-acetate or malononitrile to give 14 and 15, respectively. In this work, we have studied the anti-cancer activity of the synthesized thienopyrimidinone derivatives against MCF-7 and MCF-10A cancer cells. Furthermore, in vivo experiments showed that the synthesized compounds significantly reduced tumor growth up to the 8th day of treatment in comparison to control animal models. Additionally, the synthesized derivatives showed potential inhibitory effects against pim-1 kinase activities.

Synthesis and Molecular Docking of New Thiophene Derivatives as Lactate Dehydrogenase-A Inhibitors.

BACKGROUND & OBJECTIVE: A series of novel derivatives possessing the thiophene moiety were synthesized using ethyl 5'-amino-2,3'-bithiophene-4'-carboxylate as the starting material. METHODS: The new synthesized derivatives were screened as lactate dehydrogenase (LDH) inhibitors. LDH plays an important role in glucose metabolism in cancer cells and can affect tumor genesis and metastasis. RESULTS: 3-Substituted p-tolylthieno[2,3-d]pyrimidin-4(3H)-ones 4 were the most potent inhibitors in this study compared to Galloflavin reference drug. CONCLUSION: Molecular docking studies on the Human Lactate Dehydrogenase active site were carried out on the synthesized compounds and the MolDock scores ranged between -127 to -171.

Design, Synthesis and In-vivo Anti-inflammatory Activity of New Celecoxib Analogues as NSAID.

BACKGROUND: A new series of Celecoxib analogues were easily synthesized via reactions of 4-(2-(1-chloro-2-oxopropylidene)hydrazinyl)benzene sulfonamide (1) with active methylene compounds and dialkyl malonate. In addition, compound 1 was reacted also with thiourea derivatives and thiosemicarbazone derivatives to afford thiazole derivatives 9 and 11, respectively. Furthermore, triazolo pyrimidine derivatives 13 were prepared via reaction of compound 1 with pyrimidine thione derivatives. The structures of the new synthesized compounds were assigned by elemental analysis and spectroscopic data. The new analogues were screened for their in vivo anti-inflammatory activity using carrageenan-induced paw edema method. CONCLUSION: They showed moderate to good in vivo anti-inflammatory effects. Compounds 1, 6 and 11b were the most active compounds that reduced the paw edema induced by carrageenan by 12.25 %, 12.96 % and 12.97% respectively, as compared to the Indomethacin that inhibited the oedema volume by 7.47 %.

Sputtered Gum metal thin films showing bacterial inactivation and biocompatibility.

Super-elastic Titanium based thin films Ti-23Nb-0.7Ta-2Zr-(O) (TNTZ-O) and Ti-24Nb-(N) (TN-N) (at.%) were deposited by direct current magnetron sputtering (DCMS) in different reactive atmospheres. The effects of oxygen doping (TNTZ-O) and/or nitrogen doping (TN-N) on the microstructure, mechanical properties and biocompatibility of the as-deposited coatings were investigated. Nano-indentation measurements show that, in both cases, 1sccm of reactive gas in the mixture is necessary to reach acceptable values of hardness and Young's modulus. Mechanical properties are considered in relation to the films compactness, the compressive stress and the changes in the grain size. Data on Bacterial inactivation and biocompatibility are reported in this study. The biocompatibility tests showed that O-containing samples led to higher cells proliferation. Bacterial inactivation was concomitant with the observed pH and surface potential changes under light and in the dark. The increased cell fluidity leading to bacterial lysis was followed during the bacterial inactivation time. The increasing cell wall fluidity was attributed to the damage of the bacterial outer cell which losing its capacity to regulate the ions exchange in and out of the bacteria.

Socioeconomic status and chronic kidney disease at presentation to a renal service in the United Kingdom.

BACKGROUND AND OBJECTIVES: Low socioeconomic status (SES) is associated with both development and progression of chronic kidney disease (CKD). The impact of SES on severity of CKD at presentation to a renal service is less well known. This study investigated the relationship between SES and severity of CKD in a retrospective, cross-sectional analysis involving 1657 patients at the Sheffield Kidney Institute (Sheffield, UK). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: SES was assigned to each patient according to electoral ward of residence by postcode and ranked according to the corresponding British Index of Multiple Deprivation score, which comprises five deprivation quintiles (Q1, least deprived; Q5, most deprived). National Kidney Foundation Kidney Disease Outcomes Quality Initiative classification of CKD was used for stratification and analysis. Binary logistic regression analysis was applied for the association of variables/risk factors with CKD (lower GFR) at presentation. RESULTS: The age-adjusted prevalence of diagnosed CKD at presentation by area of residence, across the five deprivation quintiles, per million population was Q1 = 1495, Q2 = 3530, Q3 = 3398, Q4 = 3989, and Q5 = 19,599. Logistic regression models showed that living in the lowest SES quintile area (Q5) as compared with the highest SES (Q1) was associated with a greater risk for presenting with a lower estimated GFR, after adjustment for sociodemographic, lifestyle, and clinical variables. CONCLUSIONS: Low SES is related to severity of CKD at presentation. Further studies are needed to examine this issue across the various SES categories in the United Kingdom.