Carbonic anhydrase inhibitors. Inhibition of the cytosolic and tumor-associated carbonic anhydrase isozymes I, II and IX with some 1,3,4-oxadiazole- and 1,2,4-triazole-thiols

Novel mercapto-1,3,4-oxadiazole and -1,2,4-triazole derivatives were synthesized by various pathways starting from 4-(4-halogeno-phenylsulfonyl)benzoic acid hydrazides which were reacted with carbon disulfide or isothiocyanates. The heterocyclic mercaptans prepared in this way were assayed as inhibitors of three physiologically relevant isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), i.e., the cytosolic CA I and II, and the tumor-associated, transmembrane isozyme CA IX. Interesting biological activity was detected for some of the new mercaptans, with inhibition constants in the low micromolar range

Sinteza, caracterizarea şi evaluarea fitobiologică a unei noi 2-[4-(4-bromofenilsulfonil) fenil]-4-metiloxazol - 5(4H)-one şi a unor noi 5-aril -2-[4-(4-bromofenilsulfonil) fenil]- 4-metiloxazoli

“Carol Davila“ University of Medicine and Pharmacy, Faculty of Pharmacy, Bucharest, Romania, Romanian Academy, “Costin D. Nenitescu“ Centre of Organic Chemistry, Bucharest, RomaniaPurpose. Heterocyclic compounds containing 1,3-oxazol-5(4H)-one and 1,3-oxazole ring are important targets in synthetic and medicinal chemistry, because of their applications as potentially active compounds. Thus, some 1,3-oxazol-5(4H)-ones have been reported to present antimicrobial and antitumor activity. 1,3-Oxazoles are frequent substructures in various biologically active compounds used in therapeutics as anti-inflammatory (e.g. Oxaprozin, Romazarit, Ditazol, Isamoxole), analgesic (e.g. Oxaprozin), antibacterial, antifungal (e.g. Sulfamoxole, Sulfaguanole), muscle relaxant (e.g. Azumolene) drugs. Therefore, there is considerable interest to synthesize new 1,3-oxazole- 5(4H)-ones and 1,3-oxazoles which contain 4-(4-bromophenylsulfonyl) phenyl moiety in 2 position with a hope to obtain potent biologically active compounds. The plant growth regulatory effects of the new compounds were examined. Material and Methods. By Steiger N-acylation of α-alanine with 4-(4-bromophenylsulfonyl)benzoyl chloride at cool afforded 2-[4-(4-bromophenylsulfonyl) benzamido] propanoic acid. This compound underwent intramolecular cyclization in the presence of N-methylmorpholine and ethyl chloroformate or acetic anhydride to the corresponding saturated azlactone. Then, acylaminoacylation of dry aromatic hydrocarbons (benzene, toluene, m-xylene, mesitylene) with 2-[4-(4-bromophenylsulfonyl)phenyl]-4- methyloxazol-5(4H)-one or 2-[4-(4-bromophenylsulfonyl) benzamido]propanoyl chloride in the presence of anhydrous aluminum chloride led to N-(1-aryl-1- oxopropan-2-yl)-4-(4-bromophenylsulfonyl)benzamides. These new intermediates were heterocyclized under the action of phosphorus oxychloride or concentrated sulfuric acid in the presence of acetic anhydride in ethyl acetate to the corresponding 5-aryl-2-[4- (4-bromophenylsulfonyl)phenyl]-4-methyloxazoles. The structure of new compounds was confirmed by elemental analysis and different spectral methods (FT-IR, UV, MS, 1H- and 13C-NMR). The purity of the compounds was evaluated by RP-HPLC. The new compounds have been investigated for their biological activities in the growth regulation of wheat, using the phytobiological method, known as the Constantinescu bioassay – Triticum test. Results. Ten new compounds were synthesized and characterized in orther to evaluate their biological activity. The preliminary results indicated that the tested compounds exhibited a weak stimulatory activity, except of α-acylaminoketones. Conclusions. In conclusion, in this paper we described the synthesis, characterization and phytobiological activity of ten new compounds possessing the 4-(4-bromophenylsulfonyl)phenyl moiety

Synthesis, Spectral and Thermal Studies of New Rutin Vanadyl Complexes

Complexes between oxovanadium (IV) cation and flavonoid derivatives were developed recently in order to increase the intestinal absorption and to reduce the toxicity of vanadium compounds. For these reasons, is interesting to investigate the complexation process between flavonoid rutin (Rut) and vanadyl cation in order to isolate new complexes. Two new complexes [VO(Rut)(H2O)2](SO4)0.5×2H2O and [VO(Rut)2]×4H2O have been obtained and characterized by elemental and thermal analyses and several spectroscopic techniques (ESI-MS, IR, UV-Vis, fluorescence). The studies concerning complex formation between vanadyl and rutin (Rut) performed in different solutions show the formation of mononuclear complexes with 1:1 and 1:2 metal to ligand stoichiometry

Synthesis and Antioxidant Activity Evaluation of New Compounds from Hydrazinecarbothioamide and 1,2,4-Triazole Class Containing Diarylsulfone and 2,4-Difluorophenyl Moieties

In the present investigation, new hydrazinecarbothioamides 4–6 were synthesized by reaction of 4-(4-X-phenylsulfonyl)benzoic acids hydrazides (X= H, Cl, Br) 1–3 with 2,4-difluorophenyl isothiocyanate and further these were treated with sodium hydroxide to obtain 1,2,4-triazole-3-thione derivatives 7–9. The reaction of 7–9 with α-halogenated ketones, in basic media, afforded new S-alkylated derivatives 10–15. The structures of the synthesized compounds have been established on the basis of 1H-NMR, 13C-NMR, IR, mass spectral studies and elemental analysis. The antioxidant activity of all compounds has been screened. Hydrazinecarbothioamides 4–6 showed excellent antioxidant activity and 1,2,4-triazole-3-thiones 7–9 showed good antioxidant activity using the DPPH method

Synthesis and Characterization of New 5-Aryl-2-[para- -(4-chlorophenylsulfonyl)phenyl]-4-methyloxazoles

Oxazoles and 5(4H)-oxazolones are five-membered heterocyclic compounds that have a large number of applications in medicinal, agrochemical products, optical materials, etc. and have been used as highly versatile intermediates in the synthesis of a variety of organic molecules. The wide range of biological activities of oxazoles includes pharmaceutical properties such as anti- * email: [email protected] In continuation of the previous part in this series Experimental part Melting points were measured on a Böetius apparatus and are uncorrected. FT-IR spectra were registered on a Bio-Rad FTS-135 IR spectrophotometer using the standard KBr pellet disc technique, in the 4000-400 cm -1 region. UV spectra were recorded in methanolic solution (2.5 x10 -5 M) on an Analytik Jena SPECORD 40 spectrophotometer, within the range 200-600 nm. NMR spectra were recorded on a Varian Gemini 300BB apparatus, operating at 300 MHz for 1 H-NMR and 75 MHz for 13 C-NMR, using DMSO-d 6 and CDCl 3 as solvents. Chemical shifts are expressed in parts per million downfield from tetramethylsilane (TMS) as an internal standard and coupling constants are given in hertz (where, s = singlet, d = doublet, dd = double doublet, t = triplet, tt = triple triplet, q = quartet, cv = quintet, m = multiplet). Elemental analyses for C, H, N and S was obtained using a Carlo-Erba Analyser Series L-1108 apparatus. Preparation of 4-(4-chlorophenylsulfonyl)benzoyl chloride (2) 4-(4-Chlorophenylsulfonyl)benzoic acid 1 (5.93 g, 20 mmol) was converted into the corresponding acid chlorid

Preparation and Characterization of Dextran Coated Iron Oxide Nanoparticles Thin Layers

In the present study, we report the synthesis of a dextran coated iron oxide nanoparticles (DIO-NPs) thin layer on glass substrate by an adapted method. The surface morphology of the obtained samples was analyzed by Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), optical, and metallographic microscopies. In addition, the distribution of the chemical elements into the DIO-NPs thin layer was analyzed by Glow Discharge Optical Emission Spectrometry (GDOES). Furthermore, the chemical bonds formed between the dextran and iron oxide nanoparticles was investigated by Fourier Transform Infrared Spectroscopy (FTIR). Additionally, the HepG2 viability incubated with the DIO-NPs layers was evaluated at different time intervals using MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The goal of this study was to obtain a DIO-NPs thin layer which could be used as a coating for medical devices such as microfluidic channel, microchips, and catheter. The results of the surface morphology investigations conducted on DIO-NPs thin layer suggests the presence of a continuous and homogeneous layer. In addition, the GDOES results indicate the presence of C, H, Fe, and O signal intensities characteristic to the DIO-NPs layers. The presence in the IR spectra of the Fe-CO metal carbonyl vibration bonds prove that the linkage between iron oxide nanoparticles and dextran take place through carbon–oxygen bonds. The cytotoxicity assays highlighted that HepG2 cells morphology did not show any noticeable modifications after being incubated with DIO-NPs layers. In addition, the MTT assay suggested that the DIO-NPs layers did not present any toxic effects towards HEpG2 cells

Acylhydrazones and Their Biological Activity: A Review

Due to the structure of acylhydrazones both by the pharmacophore –CO–NH–N= group and by the different substituents present in the molecules of compounds of this class, various pharmacological activities were reported, including antitumor, antimicrobial, antiviral, antiparasitic, anti-inflammatory, immunomodulatory, antiedematous, antiglaucomatous, antidiabetic, antioxidant, and actions on the central nervous system and on the cardiovascular system. This fragment is found in the structure of several drugs used in the therapy of some diseases that are at the top of public health problems, like microbial infections and cardiovascular diseases. Moreover, the acylhydrazone moiety is present in the structure of some compounds with possible applications in the treatment of other different pathologies, such as schizophrenia, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. Considering these aspects, we consider that a study of the literature data regarding the structural and biological properties of these compounds is useful