Mehmet Ay

Cyclic cascade carbopalladation reactions as a route to benzene and fulvene derivatives

Abstract Palladium-catalyzed cyclization of appropriately structured triynes, haloalkenyldiynes, or haloalkenylalkyne-alkyne mixtures can provide the corresponding benzene derivatives, while the Pd-catalyzed intermolecular reaction of diynes with alkenyl halides can give fulvene derivatives.

Highly stereoselective and general synthesis of (z)-3-methyl-2-alken-1-ols via palladium-catalyzed cross coupling of (z)-3-iodo-2-buten-1-ol with organozincs and other organometals

Abstract The reaction of Zn-protected (Z)-3-iodo-2-buten-1-ol with organozincs in the presence of 1–5 mol% of a Pd complex, e.g., Pd(PPh3)4 or Cl2Pd(PPh3)2 and n-BuLi (2 equiv), in DMF provides a highly stereoselective (> -96%), general, and high-yielding procedure for preparing (Z)-3-methyl-2-alken-1-ols, while the use of organometals containing B and Sn along with a Pd catalyst or organocoppers alone gives the desired products in moderate to good yields.

Selective synthesis of benzene derivatives via palladium-catalyzed cascade carbometallation of alkynes

Abstract A Pd-catalyzed partially intermolecular cascade cyclic carbometallation of haloenynes with monoynes provides a “pair”-selective and regioselective route to benzene derivatives.

Antioxidant phenolic compounds from the leaves of Erica Arborea (Ericaceae).

Reversed-phase HPLC analyses of the methanol extract of the leaves of Erica arborea afforded a novel phenylpropanoid glucoside, named ericarborin, together with five flavonoids, dihydromyricetin 3-O-α-L-rhamnopyranoside, quercetin 3-O-β-D-glucopyranoside, quercetin 3-O-α-L-rhamnopyranoside, apigenin 7-O-β-D-glucopyranoside and apigenin 7-O-β-D-(6-O-acetyl-glucopyranoside). While the structure of ericarborin was determined by extensive 1D and 2D NMR analyses, the structures of all known flavonoids were determined by direct comparison of their spectroscopic data with respective literature data. The antioxidant properties of these compounds were assessed by the DPPH assay. The chemotaxonomic significance of these phenolic compounds has been discussed.

Effect of Copper (I) Iodide and Magnesium Chloride on Amination of Aryl Grignards with Ketoximes

Abstract Acetone oxime O-mesitylenesulphonate is shown to be a convenient reagent for amination of aryl Grignard reagents in ether-toluene in the presence of a catalytic amount of copper (I) iodide or magnesium chloride.

Tricetin 4′-O-α-L-rhamnopyranoside: A new flavonoid from the aerial parts of Erica arborea

Reversed-phase preparative HPLC purification of the methanol (MeOH) extract of the aerial parts of Erica arborea resulted in the isolation of a new flavonoid glycoside, tricetin 4′-O-α-L-rhamnopyranoside, together with the known flavonoid, isorhamnetin 3-O-α-L-rhamnopyranoside. The structures of these compounds were determined by spectroscopic means. The antioxidant properties of these compounds were assessed by the DPPH assay.

Comparative Study of Antioxidant Properties and Total Phenolic Content of the Extracts of Humulus lupulus L. and Quantification of Bioactive Components by LC–MS/MS and GC–MS

In this research, antioxidant activities of various extracts obtained from Humulus lupulus L. were compared by DPPH, ABTS, FRAP, and CUPRAC assays. The amount of total phenolic components determined by the Folin-Ciocalteu reagent was found to be highest for 25% aqueous ethanol (9079 ± 187.83 mg Ferulic acid equivalent/100 g extract) and methanol-1 (directly) (8343 ± 158.39 mg Ferulic acid equivalent/100 g extract) extracts. The n-hexane extract of H. lupulus exhibited the greatest with DPPH (14.95 ± 0.03 μg Trolox equivalent/g sample). The highest phenolic content in the ethanolic extract could be the major contributor to its highest CUPRAC activity (3.15 ± 0.44 mmol Trolox equivalent/g sample). Methanol-2 (n-hexane, acetone, and methanol) and methanol-3 (n-hexane, dichloromethane, ethylacetate, and methanol) extracts, respectively, exhibited the most potent ABTS (7.35 ± 0.03 mM Trolox equivalent) and FRAP (1.56 ± 0.35 mmol Fe(2+)/g sample) activities. Some of the components from the crude extracts were determined by LC-MS/MS and GC-MS analyses. Comparative screening of antioxidant activities of H. lupulus extracts and quantification of some major components by LC-MS/MS, qualitatively analysis of the reported ones which were optimal under negative ion SIM mode and coinjection, are going to be valuable for food and health applications.

Biological evaluation and molecular docking studies of nitro benzamide derivatives with respect to in vitro anti-inflammatory activity

&NA; A series of nitro substituted benzamide derivatives were synthesized and evaluated for their potential anti‐inflammatory activities in vitro. Firstly, all compounds (1–6) were screened for their inhibitory capacity on LPS induced nitric oxide (NO) production in RAW264.7 macrophages. Compounds 5 and 6 demonstrated significantly high inhibition capacities in a dose‐dependent manner with IC50 values of 3.7 and 5.3 &mgr;M, respectively. These two compounds were also accompanied by no cytotoxicity at the studied concentrations (max 50 &mgr;M) in macrophages. Molecular docking analysis on iNOS revealed that compounds 5 and 6 bind to the enzyme more efficiently compared to other compounds due to having optimum number of nitro groups, orientations and polarizabilities. In addition, 5 and 6 demonstrated distinct regulatory mechanisms for the expression of the iNOS enzyme at the mRNA and protein levels. Specifically, both suppressed expressions of COX‐2, IL‐1&bgr; and TNF‐&agr; significantly, at 10 and 20 &mgr;M. However, only compound 6 significantly and considerably decreased LPS‐induced secretion of IL‐1&bgr; and TNF‐&agr;. These results suggest that compound 6 may be a multi‐potent promising lead compound for further optimization in structure and as well as for in vivo validation studies. Graphical abstract: Figure. No caption available. HighlightsSix (1‐6) nitro substituted benzamide derivatives were synthesized.Their anti‐inflammatory activities were screened by nitric oxide inhibition assay in LPS induced RAW264.7 macrophages.Two lead compounds were identified and investigated for NO inhibitory IC50 values and dose‐response relations.Molecular docking studies on iNOS enzyme supported the biological data.The effects of lead compounds on iNOS, COX‐2, IL‐1&bgr; and TNF‐&agr; expression were investigated.

Antiproliferative activity of Humulus lupulus extracts on human hepatoma (Hep3B), colon (HT-29) cancer cells and proteases, tyrosinase, β-lactamase enzyme inhibition studies

Abstract The aims of this study were to examine the antiproliferation of Humulus lupulus extracts on human hepatoma carcinoma (Hep3B) and human colon carcinoma (HT-29) cell lines along with enzyme inhibitory effects of the crude extracts. Potential cell cytotoxicity of six different H. lupulus extracts were assayed on various cancer cells using MTT assay at 24, 48 and 72 h intervals. Methanol-1 extract has inhibited the cell proliferation with doses of 0.6–1 mg/mL in a time dependent (48 and 72 hours) manner in Hep3B cells with 70% inhibition, while inhibitory effect was not seen in colon cancer cells. Acetone extract has increased the cell proliferation at low doses of 0.1 mg/mL for 72 h in Hep3B cells and 0.1–0.2 mg/mL for 48 and 72 h in HT29 cells. The inhibitory effects of the extracts were compared by relative maximum activity values (Vmax) using proteases such as α-chymotrypsin, trypsin and papain, tyrosinase and β-lactamase (penicillinase).

Prodrugs For Nitroreductase Based Cancer Therapy- 1 Metabolite Profile, Cell Cytotoxicity and Molecular Modeling Interactions of Nitro Benzamides with Ssap-NtrB

BACKGROUND Directed Enzyme Prodrugs Therapy (DEPT) as an alternative method against conventional cancer treatments, in which the non-toxic prodrugs is converted to highly cytotoxic derivative, has attracted an ample attention in recent years for cancer therapy studies. OBJECTIVE The metabolite profile, cell cytotoxicity and molecular modeling interactions of a series of nitro benzamides with Ssap-NtrB were investigated in this study. METHOD A series of nitro-substituted benzamide prodrugs (1-4) were synthesized and firstly investigated their enzymatic reduction by Ssap-NtrB (S. saprophyticus Nitroreductase B) using HPLC analysis. Resulting metabolites were analyzed by LC-MS/MS. Molecular docking studies were performed with the aim of investigating the relationship between nitro benzamide structures (prodrugs 1-4) and Ssap-NtrB at the molecular level. Cell viability assay was conducted on two cancer cell lines, hepatoma (Hep3B) and colon (HT-29) cancer models and healthy cell model HUVEC. Upon reduction of benzamide prodrugs by Ssap-NtrB, the corresponding amine effectors were tested in a cell line panel comprising PC-3, Hep3B and HUVEC cells and were compared with the established NTR substrates, CB1954 (an aziridinyl dinitrobenzamide). RESULTS Cell viability assay resulted in while prodrugs 1, 2 and 3 had no remarkable cytotoxic effects, prodrug 4 showed the differential effect, showing moderate cytotoxicity with Hep3B and HUVEC. The metabolites that obtained from the reduction of nitro benzamide prodrugs (1-4) by Ssap-NtrB, showed differential cytotoxic effects, with none toxic for HUVEC cells, moderate toxic for Hep3B cells, but highly toxic for PC3 cells. CONCLUSION Amongst all metabolites of prodrugs after Ssap-NtrB reduction, N-(2,4- dinitrophenyl)-4-nitrobenzamide (3) was efficient and toxic in PC3 cells as comparable as CB1954. Kinetic parameters, molecular docking and HPLC results also confirm that prodrug 3 is better for Ssap-NtrB than 1, 2 and 4 or known cancer prodrugs of CB1954 and SN23862, demonstrating that prodrug 3 is an efficient candidate for NTR based cancer therapy.