Phosphorylation of polyprenols by phosphorous acid amides

Phosphorylation of the hydroxyl group of polyprenol by amides of phosphorous acid with the purpose of producing novel bioactive compounds has been investigated. Di- and monoamidophosphites and thiophosphates of polyprenol have been obtained. Their structure has been confirmed by ³¹P-, ¹H-, and ¹³C NMR spectroscopy and MALDI-TOF mass spectrometry.     

N alpha-arylsulfonyl-omega-amidinophenyl-alpha-aminoalkyl-carboxylic acid amides as specific thrombin inhibitors

Structure-activity relationships for the inhibition of thrombin and trypsin by N alpha-substituted amidinophenyl-alpha-aminoalkylcarboxylic acid amides are presented. Secondary cyclic amides of N alpha-substituted 4-amidinophenylalanine and 2-amino-5-(4-amidinophenyl)valeric acid were found to be potent and specific inhibitors of thrombin, whereas trypsin was inhibited strongly by primary amides of 2-amino-4-(4-amidinophenyl) butyric acid. For this type of inhibitor the carbon amide structure seems to play a decisive role in the enzyme-inhibitor interaction.     

The preparation of bile acid amides and oxazolines

Amides obtained by the condensation of some bile acid chlorides with 2-amino-2-methyl-l-propanol on cyclization yield bile acid oxazolines. Physical properties of these bile acid derivatives are described. Some of the oxazolines are non-toxic and are inhibitors of 7-dehydroxylaseactivity in fecal anaerobic bacteria and purified enzymes from these bacteria.     

Identification of fatty acid amides in human plasma

A family of five long-chain fatty acid carboxamides has been identified and semi-quantified in human plasma by GC-MS. One saturated and four unsaturated amides were found. Luteal phase plasma from 16 women was studied, and all five of the amides were found in ten of the subjects, but none in the other six. The structure of these endogenous amides was established by comparing their GC and MS characteristics with those of the synthetic amides prepared by ammonolysis of corresponding long-chain fatty acid acyl chlorides.     

The preparation of bile acid amides and oxazolines, II, the synthesis of the amides and oxazolines of ursodeoxycholic acid, deoxycholic acid, hyodeoxycholic acid and cholic acid

Bile acid amides and oxazolines were synthesized by a sequence of steps involving the reaction of the free bile acid with formic acid to yield the formyloxy derivative, preparation of the formyloxy acid chloride, condensation of the acid chloride with 2-amino-2-methyl-1-propanol to give the amide and, finally, cyclization of the amide with thionyl chloride to give the oxazoline. The oxazolines were characterized by physical constants, thin layer and gas-liquid chromatography and identified by elemental analysis and gas-liquid chromatography-mass spectrometry. Some of the bile acid oxazoline derivatives alter the activity of bacterial 7-dehydroxylases $\text{in vitro}$, and inhibit the growth of certain anaerobic bacteria in pure culture.     

The distribution of hydroxycinnamic acid amides in flowering plants

Hydroxycinnamic acid amides have been identified as the main phenolic constituents in the reproductive organs of a range of flowering plants.     

Synthesis and proapoptotic activity of oleanolic acid derived amides

Thirty-one different 3-O-acetyl-OA derived amides have been prepared and screened for their cytotoxic activity. In the SRB assays nearly all the carboxamides displayed good cytotoxicity in the low μM range for several human tumor cell lines. Low EC₅₀ values were obtained especially for the picolinylamides 14–16, for a N-[2-(dimethylamino)-ethyl] derivative 27 and a N-[2-(pyrrolinyl)-ethyl] carboxamide 28. These compounds were submitted to an extensive biological testing and proved compound 15 to act mainly by an arrest of the tumor cells in the S phase of the cell cycle. Cell death occurred by autophagy while compounds 27 and 28 triggered apoptosis.     

Aliphatic acid amides of the fruits of Zanthoxylum piperitum

Six aliphatic acid amides (1-6) were isolated from the pericarp of Zanthoxylum piperitum fruits. MS and NMR spectroscopic investigation revealed that these compounds have a ketone and/or hydroxyl group(s) in the unsaturated aliphatic acid moiety of the structure of the amides. Combinations 3-4 and 5-6 are stereoisomers in terms of the relative configurations of their two asymmetric carbons.     

Synthesis and antituberculosis activity of new fatty acid amides

This work reports the synthesis of new fatty acid amides from C16:0, 18:0, 18:1, 18:1 (OH), and 18:2 fatty acids families with cyclic and acyclic amines and demonstrate for the first time the activity of these compounds as antituberculosis agents against Mycobacterium tuberculosis H₃₇Rv, M. tuberculosis rifampicin resistance (ATCC 35338), and M. tuberculosis isoniazid resistance (ATCC 35822). The fatty acid amides derivate from ricinoleic acid were the most potent one among a series of tested compounds, with a MIC 6.25 μg/mL for resistance strains.     

The enzymatic formation of novel bile acid primary amides

Bifunctional peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the copper-, ascorbate-, and O(2)-dependent cleavage of C-terminal glycine-extended peptides and N-acylglycines to the corresponding amides and glyoxylate. The alpha-amidated peptides and the long-chain acylamides are hormones in humans and other mammals. Bile acid glycine conjugates are also substrates for PAM leading to the formation of bile acid amides. The (V(MAX)/K(m))(app) values for the bile acid glycine conjugates are comparable to other known PAM substrates. The highest (V(MAX)/K(m))(app) value, 3.1 +/- 0.12 x 10(5) M(-1) s(-1) for 3-sulfolithocholylglycine, is 6.7-fold higher than that for d-Tyr-Val-Gly, a representative peptide substrate. The time course for O(2) consumption and glyoxylate production indicates that bile acid glycine conjugate amidation is a two-step reaction. The bile acid glycine conjugate is first converted to an N-bile acyl-alpha-hydroxyglycine intermediate which is ultimately dealkylated to the bile acid amide and glyoxylate. The enzymatically produced bile acid amides and the carbinolamide intermediates were characterized by mass spectrometry and two-dimensional (1)H-(13)C heteronuclear multiple quantum coherence NMR.     

Targeted lipidomics: fatty acid amides and pain modulation

Mass spectrometric approaches to the identification and quantification of lipid signalling molecules are reviewed. Fatty acid amides are an important new class of lipid signalling molecules which include oleamide, the endocannabinoid anandamide, the endovanilloid/endocannabinoid N-arachidonoyldopamine (NADA) and the endovanilloid N-oleoyldopamine (OLDA) among many others. This diverse group of endogenous compounds comprises combinations of acyl backbones coupled by an amide bond to any of a variety of different small polar molecules such as ethanolamine, various amino acids, and catecholamines. Many fatty acid amides appear to play a role in pain and inflammation. Targeted lipidomics of fatty acid amides aims to identify new members of this diverse class of compounds, of which only a few representative molecules have been characterized to date. This effort has been made feasible by advances in chromatography and mass spectrometry, which permits: (1) identification of compounds present in complex mixtures, (2) astronomical increases in sensitivity due to miniaturization of HPLC components, and (3) novel scanning modes that permit the identification of compounds exhibiting similar structural components. Insofar as lipid signalling molecules such as prostanoids, leukotrienes and endocannabinoids operate via G-protein coupled receptors (GPCR), it appears likely that many of the numerous lipids awaiting identification may serve as ligands for any of the greater than 150 orphan GPCRs.     

Synthesis and evaluation of caffeic acid amides as antioxidants

A series of amides of caffeic acid has been synthesised and their antioxidant properties evaluated as lipid peroxidation inhibitors. Anilides of caffeic acid were found to be very efficient antioxidants with IC50's of 0.3 microM.     

Fatty acid amides from freshwater green alga Rhizoclonium hieroglyphicum

Freshwater green algae Rhizoclonium hieroglyphicum growing in the Ural Mountains were examined for their fatty acid amides using capillary gas chromatography-mass spectrometry (GC-MS). Eight fatty acid amides were identified by GC-MS. (Z)-9-octadecenamide was found to be the major component (2.26%).     

Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D inhibitors

Gallic acid, one of the most abundant plant phenolic acids, has been modified to cathepsin D protease inhibitors. The strategy of modification was proposed basing on some previously reported structure and activity relationship (SAR) studies. The synthesized naphthophenone fatty acid amide derivatives have been evaluated for in vitro cathepsin D inhibition activity. Two of them have shown significant inhibition activity with IC(50) values of 0.06 and 0.14 microM, respectively, as compared against pepstatin (0.0023 microM), the most potent inhibitor known so far. The study revealed that such attempts on gallic acid based pharmacophores might result in potent inhibitors of cathepsin D.     

Synthesis and biological activity of retinoic acid receptor-alpha specific amides

Retinoids are analogues of all-trans-retinoic acid, a powerful hormone that mediates many fundamental biological processes. Cancer and other serious hyperproliferative diseases are attractive therapeutic targets for retinoids, but the therapeutic use of retinoids is limited due to severe toxicity. We report here the design of retinoid receptor-alpha specific ligands with growth inhibitory activity in breast cancer cell lines, and which do not cause the cutaneous toxicity associated with the currently available nonselective retinoid agonists.