Catalytic and Biological Activity of Silver and Gold Complexes Stabilized by NHC with Hydroxy Derivatives on Nitrogen Atoms

In this paper is reported the synthesis of N,N′ hydroxy derivative of NHC silver (3a–4a) and gold(I) (3b–4b) complexes of general formula [M(NHC)2]+ [MX2]−. All compounds were characterized by spectroscopic and analytic techniques. The complexes turned out to be effective in both catalytic and biological applications. They catalyzed the coupling of aldehyde, piperidine, and phenylacetylene in A3-reaction to produce propargylamines and showed antimicrobial activity. In fact, minimal inhibition concentration (MIC) tests with Gram-positive and Gram-negative bacteria demonstrated that the silver compounds are selective toward E. coli, whereas the gold analogues are active against S. aureus. Moreover, the N,N′ hydroxy derivative of NHC silver complexes 3a and 4a exhibited good anticancer activity on the HeLA cancer cells (3a-IC50 = 12.2 ± 0.1 µM, 4a-IC50 = 11.9 ± 1.2 µM), whereas gold complex 4b displayed good anticancer activity towards the MCF-7 cells (IC50 = 12.2 ± 1.2 µM).

Metabolic Profiles of New Unsymmetrical Bisacridine Antitumor Agents in Electrochemical and Enzymatic Noncellular Systems and in Tumor Cells

New unsymmetrical bisacridines (UAs) demonstrated high activity not only against a set of tumor cell lines but also against human tumor xenografts in nude mice. Representative UA compounds, named C-2028, C-2045 and C-2053, were characterized in respect to their physicochemical properties and the following studies aimed to elucidate the role of metabolic transformations in UAs action. We demonstrated with phase I and phase II enzymes in vitro and in tumors cells that: (i) metabolic products generated by cytochrome P450 (P450), flavin monooxygenase (FMO) and UDP-glucuronosyltransferase (UGT) isoenzymes in noncellular systems retained the compound’s dimeric structures, (ii) the main transformation pathway is the nitro group reduction with P450 isoenzymes and the metabolism to N-oxide derivative with FMO1, (iii), the selected UGT1 isoenzymes participated in the glucuronidation of one compound, C-2045, the hydroxy derivative. Metabolism in tumor cells, HCT-116 and HT-29, of normal and higher UGT1A10 expression, respectively, also resulted in the glucuronidation of only C-2045 and the specific distribution of all compounds between the cell medium and cell extract was demonstrated. Moreover, P4503A4 activity was inhibited by C-2045 and C-2053, whereas C-2028 affected UGT1A and UGT2B action. The above conclusions indicate the optimal strategy for the balance among antitumor therapeutic efficacy and drug resistance in the future antitumor therapy.

Changes in cell membranes of white blood cells treated with a common food additive E407a

Objectives To estimate the state of phospholipid bilayer of rats WBCs exposed to a common food additive E407a, which is used as a thickener and emulsifier, during 4 h using a fluorescent probe − ortho-hydroxy derivative of 2,5-diaryl-1,3-oxazole. Materials and methods Steady-state fluorescence spectroscopy: a study by the environment-sensitive fluores-cent probe − 2-(2′-hydroxy-phenyl)-5-phenyl-1,3-oxazole (probe O1O). Results Changes are detected in the spectra of the fluorescent probe bound to rat WBCs treated with the solutions of E407a of various concentrations in comparison with the corresponding spectra of the probe incubated with the untreated leukocytes. The decrease in polarity and proton-donor ability is observed in the lipid membranes of leukocytes in the region, where the probe locates. Conclusions Our findings suggest a higher dehydration of leukocyte membranes of rats treated with a common food additive E407a at high concentrations and, thus, indicate that exposure to high doses of E407a leads to the increase in the lipid order (i.e. to decrease in fluidity) of the membranes of rat WBCs.

Determination of narciclasine in mouse blood by UPLC-MS/MS and its application to a pharmacokinetic study

Narciclasine is a 7-hydroxy derivative of lycorisidine. It was the first alkaloid isolated from the stem of narcissus (Amaryllidaceae) in 1967. Six mice were given narciclasine (5 mg/kg) by intravenous administration. A UPLC-MS/MS method was developed to determine narciclasine in mouse blood. Tectorigenin (internal standard, IS) and narciclasine were gradient eluted by mobile phase of methanol and 0.1% formic acid in a BEH C18 column. The multiple reaction monitoring (MRM) of m/z 308.1→248.1 for narciclasine and m/z 301.1→286.0 for IS with an electrospray ionization (ESI) source was used for quantitative determination. The calibration curve ranged from 1 to 6,000 ng/mL. The accuracy was from 92.5 to 107.3%, and the matrix effect was between 103.6 and 107.4%. The developed UPLC-MS/MS method was successfully applicated to a pharmacokinetic study of narciclasine in mice after intravenous administration (5 mg/kg).

Alumina-K3PO4 Solid Supported Microwave Synthesis of 1, 3-diaryl-2- propene-1-one Derivatives as a Prominent Antioxidant Scavenger

Background: The various industrial processes have a diverse effect on the environment through pollution. In view of these observations, some environmentally benign synthetically protocols have developed under green chemistry. For rapid and sustainable synthesis, the microwave irradiation (MI) has gained popularity as a powerful tool compared to conventional synthesis. The present study describes the synthesis of novel substituted 1, 3-diaryl-2-propene-1-one derivative using alumina supported K3PO4-MWI combination. Objective: Chalcones are important compounds which are widely spread in nature like in fruits, vegetables, tea, spices, etc. The 2’-hydroxy derivative of chalcones plays an important role in the synthesis of bioactive compounds. The present communication deals with a convenient and rapid synthesis of 1, 3-diaryl-2-propene-1-one under the support of alumina-tripotassium phosphate and microwave irradiation. Our efforts are focused on the introduction of typical and easier route for the synthesis of title compounds using a microwave. All synthesized chalcones have been screened and evaluated for the antioxidant activity by DPPH and nitric oxide radical scavenging. Some of these compounds are found to be more potent scavengers and may lead to the development of a new class of antioxidants. Methods: The α, β-unsaturated carbonyl functionality contains two electrophilic centers allowing them to undergo addition and cyclization reactions with different nucleophiles. In the literature survey, we found that Chalcones were synthesized using tripotassium phosphate catalyst under refluxing by a conventional method. A novel method for the synthesis of 1, 3-diaryl-2-propene-1-one via Claisen Schmidt has been introduced by reacting substituted 2’- hydroxyl acetonaphthones with substituted aromatic aldehydes under the support of basic alumina –tripotassium phosphate via microwave radiations. Formation of corresponding Chalcones was confirmed by spectral studies followed by their screening for antioxidant activity. The scavenging activity is expressed in terms of % inhibition and IC50 value (μg/ml). Results: The structures of newly synthesized Chalcones were confirmed and in good agreement with obtained spectral analysis such as IR, NMR, Mass and elemental analysis. Commercially available basic alumina and tripotassium phosphate in combination of microwave were utilized and found to be effective, convenient route for the synthesis of 1, 3-diaryl-2-propene-1-one derivatives with desirable yields in short reaction time (5-12 min). The results of antioxidant activity revealed that the IC50 value for compounds 3a, 3d, 3e, 3f, 3g, 3h, 3j, 3l and 3n are lower than that of standard ascorbic acid to scavenge DPPH radical. This indicates that these compounds are more significant scavengers in comparison with standard drug. On the other hand, compounds 3a, 3b, 3c, 3d, 3g, 3l and 3n are more potent scavengers for NO free radical. Conclusion: We have introduced an efficient, ecofriendly, simple and fast microwave assisted method using basic alumina-tripotassium phosphate for the synthesis of 1, 3-diaryl-2-propene-1- one derivatives. Microwave irradiation provides an effective way for the preparation of Chalcones in terms of several advantages as a simple procedure, short reaction time, milder reaction condition, cleaner reaction and excellent yield. The scavenging activity of chalcones against DPPH and NO free radicals showed excellent properties of antioxidants.

Water-soluble diboronic acid-based fluorescent sensors recognizing d-sorbitol

Water-soluble diboronic acid sensor 15c exhibited higher selectivity for d-sorbitol than monoboronic acid sensor 1 and hydroxy derivative 2. And it could be applied for d-sorbitol sensing and analysis in real samples.

Investigation of reaction conditions on synthesis of steroidal bromohydrin and structural analysis of novel 6α-brom-5β-hydroxy derivative

Reaction conditions variation and its influence on the reaction of 3?- acetoxy-17-oxa-17a-homoandrost-5-en-16-one with in situ generated hypobromous acid was investigated. Hypobromous acid was generated from N-bromoacetamide or Nbromosuccinimide and perchloric acid, and as solvent dioxane, dimethoxyethane or tetrahydrofuran were used. After a series of experiments, it was determined that the number of the reaction products depends on the reagent used, solvents, perchloric acid concentration and the presence/absence of daylight. It has also been found that the yields of certain compounds depend also on the reaction time and temperature. 6?-Bromo-5?- hydroxy derivate is obtained by usage of NBA and 0.28 M perchloric acid in dioxane on daylight. Its structure was confirmed by NMR and X-ray crystal structure analysis.

7-Hydroxycoumarin Elicit Anti-Angiogenic Effects Through Cellular Apoptosis in Developing Embryos of Zebrafish (Danio Rerio)

Derivatives of coumarin have diverse biological activities and pharmacological significance. In this study we made an attempt to test one of the hydroxy derivative i.e. 7-hydroxycoumarin (7HC) for its anti-angiogenic potential using embryonic angiogenesis of zebrafish (Danio rerio) as biological model. Developing embryos of D. rerio were cultured in media containing one of the grade (1 mM or 2 mM or 3 mM or 4 mM or 5 mM) of concentration of 7HC from gastrula stage (~6 hrs post fertilization - hpf) until completion of embryonic development and hatching (72 hpf). Developmental trajectory of each post hatched larva was traced for two weeks. Angiogenesis and patterning of major blood vessels occurred in zebrafish embryos/ larvae between 24 - 72 hpf in controls. Exposure to 7HC resulted in an impairment in patterning of inter segmental vessels (ISVs) dorsal aorta (DA), dorsal longitudinal anastomotic vessel (DLAV), posterior cardinal vein (PCV), and common cardinal veins (CCVs) accompanied by increased site specific cellular apoptosis, declined heart rates in a dosedependent manner. 7HC manifest anti-angiogenic effects mediated/ induced through cellular apoptosis, hence may deserve attention and consideration as tumour angiogenesis suppressors in malignancy therapeutics.