- Structure-activity relationship study and biological evaluation of SAC-Garlic acid conjugates as novel anti-inflammatory agents
-
A series of S-allyl-L-cysteine (SAC) with garlic acid conjugates as anti-inflammatory agents were designed and synthesized. Among the 40 tested compounds, SMU-8c exhibited the most potent inhibitory activity to Pam3CSK4-induced nitric oxide (NO) in RAW264.7 macrophages with IC50 of 22.54 ± 2.60 μM. The structure-activity relationship (SAR) study suggested that the esterified carboxyl group, carbon chain extension and methoxylation phenol hydroxy could improve the anti-inflammatory efficacy. Preliminary anti-inflammatory mechanism studies showed that SMU-8c significantly down-regulated the levels of Pam3CSK4 triggered TNF-α cytokine in human THP-1 cells, mouse RAW 264.7 macrophages, as well as in ex-vivo human peripheral blood mononuclear cells (PBMC) with no influence on cell viability. SMU-8c specifically blocked the Pam3CSK4 ignited secreted embryonic alkaline phosphatase (SEAP) signaling with no influence to Poly I:C or LPS triggered TLR3 or TLR4 signaling. Moreover, SMU-8c suppressed TLR2 in HEK-Blue hTLR2 cells and inhibited the formation of TLR1-TLR2, and TLR2-TLR6 complex in human PBMC. In summary, SMU-8c inhibited the TLR2 signaling pathway to down-regulate the inflammation cytokines, such as NO, SEAP and TNF-α, to realize its anti-inflammatory activity.
- Bi, Jingjie,Wang, Wenqing,Du, Junxi,Chen, Kun,Cheng, Kui
-
p. 233 - 245
(2019/07/02)
-
- The application of template selectophores for the preparation of molecularly imprinted polymers
-
Molecularly imprinted polymers are versatile materials with wide application scope for the detection, capture and separation of specific compounds present in complex feed stocks. A major challenge associated with their preparation has been the need to sacrifice one mole equivalent of the template molecule to generate the complementary polymer cavities that selectively bind the target molecule. Moreover, template molecules can often be difficult to synthesise, expensive or lack stability. In this study, we describe a new approach, directed at the use of synthetic selectophores, chosen as readily prepared and low cost structural analogues with recognition groups in similar three-dimensional arrangements as found in the target molecule. To validate the approach, a comparative study of selectophores related to the polyphenolic compound (E)-resveratrol has been undertaken using traditional and green chemical synthetic approaches. These molecular mimic compounds were employed as polymer templates and also as binding analytes to interrogate the recognition sites associated with the molecularly imprinted polymers. Importantly, the study confirms that the use of selectophores has the potential to confer practical advantages, including access to more efficient methods for selection and preparation of suitable template molecules with a broader range of molecular diversity, as well as delivering imprinted polymers capable of recognizing the target compound and structurally related products.
- Danylec, Basil,Schwarz, Lachlan J.,Harris, Simon J.,Boysen, Reinhard I.,Hearn, Milton T. W.
-
p. 17601 - 17613
(2015/10/12)
-
- PREPARATION METHOD OF ACYLBENZENES
-
A process for the production of acylbenzenes, comprising reacting diacetoxybenzoyl chloride with a Grignard reagent in the presence of an iron-containing catalyst. The acylbenzenes are useful intermediates in a multistep process for the preparation of resveratrol.
- -
-
-
- PREPARATION METHOD OF ACYLBENZENES
-
A process for the production of acylbenzenes, comprising reacting diacetoxybenzoyl chloride with a Grignard reagent in the presence of an iron-containing catalyst. The acylbenzenes are useful intermediates in a multistep process for the preparation of resveratrol.
- -
-
-
- MOLECULARLY IMPRINTED POLYMERS
-
The present invention provides methods of designing molecularly imprinted polymers (MIPs) which have applications in extracting bioactive compounds from a range of bioprocessing feedstocks and wastes. The present invention is further directed to MIPs designed by the methods of the present invention.
- -
-
-
- Novel Sirtuin Activating Compounds and Methods for Making the Same
-
The present invention includes methods for preparing resveratrol, resveratrol esters and substituted and unsubstituted stilbenes of the formula given below; where each Y is —O or halogen, each Z is —O or halogen, each n and each m is independently the value of 0, 1, 2, 3, 4 or 5, each A and each B is independently selected from Pn, R or absent, each V and each W is independently selected from Pn, straight or branched alkyl of from (2) to (6) carbon atoms and cycloalkyl of from (3) to (8) carbon atoms, alkoxy, phenyl, benzyl or halogen, R is independently selected from the group comprising alkyl with at least one carbon atom, aryl and aralkyl, Pn is an alcohol protecting group and diastereoisomers of the foregoing. The compounds are made from a multi-step process including a N-heterocyclic carbon-type ligand coupling in the presence of a base with benzyol halide and styrene coupling partners. These compounds show increased stability for use in the food, cosmetic and pharmaceutical industries.
- -
-
Page/Page column 25
(2008/12/04)
-
- Synthesis of polyhydroxylated ester analogs of the stilbene resveratrol using decarbonylative Heck couplings
-
Protected 3,5-hydroxy-benzoyl chlorides 3 were coupled with styrenes 4 to give hydroxylated stilbenes, analogs of resveratrol, an important antioxidant disease preventative agent isolated from grape skins and other dietary sources. Levulinate and chloroacetate protecting groups allowed for the selective production of mono- and di-acetate variations under palladium-N-heterocyclic carbene (NHC) catalyzed decarbonylative coupling conditions. Fluorinated analogs were also produced using Heck conditions with bromofluorobenzenes. Human HL-60 cell assays showed the 4′-acetoxy variant 11 to have improved activity (ED50 17 μM) relative to resveratrol (24 μM).
- Andrus, Merritt B.,Liu, Jing
-
p. 5811 - 5814
(2007/10/03)
-
- Synthesis of selenium-containing polyphenolic acid esters and evaluation of their effects on antioxidation and 5-lipoxygenase inhibition
-
Six novel selenium-containing polyphenolic acid esters were synthesized and evaluated as antioxidants and 5-lipoxygenase inhibitors. Synthesis of the title compounds involved the Mitsunobu reaction of polyphenolic acids (4-8, 14) with 2-phenylselenoethanol (3). Compounds 22, 23, and 25 were found to be very effective antioxidants and 5-lipoxygenase inhibitors with activity comparable to or better than caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE).
- Lin, Chi-Fu,Chang, Tsu-Chung,Chiang, Chih-Chia,Tsai, Hou-Jen,Hsu, Ling-Yih
-
p. 1402 - 1407
(2007/10/03)
-
- Synthesis of resveratrol using a direct decarbonylative Heck approach from resorcylic acid
-
The phytoalexin resveratrol has been made using a decarbonylative Heck reaction. The acid chloride derived from 3,5-dihydroxybenzoic acid was coupled with 4-acetoxystyrene in the presence of palladium acetate and N,N-bis-(2,6-diisopropylphenyl)dihydroimidazolium chloride to give the substituted stilbene in 73% yield as the key step.
- Andrus, Merritt B.,Liu, Jing,Meredith, Erik L.,Nartey, Edward
-
p. 4819 - 4822
(2007/10/03)
-
- Novel Enzymatic De-esterification Studies on Substituted Polyacetoxybenzamides
-
The regioselective capabilities of porcine pancreatic lipase in tetrahydrofuran and Candida rugosa lipase in diisopropyl ether have been investigated for selective deacetylation of peracetates of primary, secondary and tertiary amides of 2-hydroxy-, 2,4-dihydroxy-, 2,5-dihydroxy-, 3,5-dihydroxy- and 3,4,5-trihydroxybenzoic acids. The lipases exhibit random selectivity for the deacetylation of ortho-, meta- and para-acetoxy functions of di/triacetoxybenzamides leading to the formation of the corresponding partially and/or completely deacetylated benzamides. The amide group of all substrates under investigation remains inert to enzymatic hydrolysis. The results of deesterification are in good agreement with our earlier proposed mechanism of action of porcine pancreatic lipase on diaryl or aryl alkyl ketones in organic solvents.
- Parmar, Virinder S.,Kumar, Ajay,Prasad, Ashok K.,Kumar, Rajesh,Bisht, Kirpal S.,Poonam,Jain, Subhash C.,Olsen, Carl E.
-
p. 810 - 822
(2007/10/03)
-
- Selective tight binding inhibitors of trypanosomal glyceraldehyde-3- phosphate dehydrogenase via structure-based drug design
-
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the sleeping sickness parasite Trypanosoma brucei is a rational target for anti- trypanosomatid drug design because glycolysis provides virtually all of the energy for the bloodstream form of this parasite. Glycolysis is also an important source of energy for other pathogenic parasites including Trypanosoma cruzi and Leishmania mexicana. The current study is a continuation of our efforts to use the X-ray structures of T. brucei and L. mexicana GAPDHs containing bound NAD+ to design adenosine analogues that bind tightly to the enzyme pocket that accommodates the adenosyl moiety of NAD+. The goal was to improve the affinity, selectivity, and solubility of previously reported 2'-deoxy-2'-(3-methoxybenzamido)adenosine (1). It was found that introduction of hydroxyl functions on the benzamido ring increases solubility without significantly affecting enzyme inhibition. Modifications at the previously unexploited N6-position of the purine not only lead to a substantial increase in inhibitor potency but are also compatible with the 2'-benzamido moiety of the sugar. For N6-substituted adenosines, two successive rounds of modeling and screening provided a 330-fold gain in affinity versus that of adenosine. The combination of N6- and 2'- substitutions produced significantly improved inhibitors. N6-Benzyl (9a) and N6-2-methylbenzyl (9b) derivatives of 1 display IC50 values against L. mexicana GAPDH of 16 and 4 μM, respectively (3100- and 12500-fold more potent than adenosine). The adenosine analogues did not inhibit human GAPDH. These studies underscore the usefulness of structure-based drug design for generating potent and species-selective enzyme inhibitors of medicinal importance starting from a weakly binding lead compound.
- Aronov, Alex M.,Verlinde, Christophe L. M. J.,Hol, Wim G. J.,Gelb, Michael H.
-
p. 4790 - 4799
(2007/10/03)
-
- 1-arylpyrimidine derivatives and pharmaceutical use thereof
-
The present invention relates to 1-arylpyrimidine derivatives represented by general formula (I): STR1 wherein R1 is H, alkyl or aralkyl; Ar is 1-naphthyl, or a substituted or unsubstituted phenyl group; R4 is a substituted phenyl, a substituted styryl, 1-methylcyclohexyl, 4-methylcyclohexyl, 4-oxo-4H-pyran-2-yl or 2-oxo-2H-pyran-5-yl group; R5 and R6 are each independently H or alkyl; R3 is H, and R7 and R8 are combined together to be oxo, or else R3 and R7 are combined together to be another direct bond, and R5 and R8 are combined together to be a direct bond, or pharmaceutically acceptable salts thereof; and methods for treating allergic diseases with such compounds.
- -
-
-
- Structure-activity relationships of non-peptide vasopressin V(1a) antagonists: 1-(1-multi-substituted benzoyl 4-piperidyl)-3,4-dihydro-2(1H)- quinolinones
-
During our systematic studies on the arginine vasopressin receptor V(1a)- antagonistic activity of 1-(1-benzoyl substituted 4-piperidyl)-3,4-dihydro- 2(1H)-quinolinones, we found a general substituent effect on the benzene ring. Hydrogen-bonding ability a
- Kondo,Ogawa,Nakaya,Tominaga,Yabuuchi
-
p. 725 - 733
(2007/10/03)
-
- H-bonded oxyhemoglobin models with substituted picket-fence porphyrins: The model compound equivalent of site-directed mutagenesis
-
Iron(II) complexes of picket-fence-type porphyrins having one of the four pivalamide pickets replaced by a substituent capable of H-bonding have been synthesized as models for oxyhemoglobin. This synthetic approach is analogous to site-directed mutagenesis of the distal residues in oxygen-binding hemoproteins. Rate and equilibrium data for dioxygen binding have been determined to evaluate the effect of the H-bonding substituent and to make comparisons with more passive substituents. The effect of H-bonding on the dioxygen affinity under standard conditions (25 °C, toluene solvent, 1,2-dimethylimidazole as axial ligand) is best illustrated by the ca. 10-fold increase observed when one pivalamide substituent of picket-fence porphyrin is replaced by a phenylurea substituent. Other substituents influence dioxygen adduct stability in a variety of ways to reveal that even with an apparently straightforward systematic approach, there can be considerable difficulty in partitioning the various factors that influence O2 affinity. This applies to both model compounds and mutant proteins.
- Wuenschell, Gerald E.,Tetreau, Catherine,Lavalette, Daniel,Reed, Christopher A.
-
p. 3346 - 3355
(2007/10/02)
-
- Disubstituted piperazines
-
Piperazines of the formula STR1 and their salts, in which each of Ar1 and Ar2, independently of the other, represents phenyl that is unsubstituted or mono- or di-substituted by C1 -C7 -alkyl, C1 -C7 -alkoxy, cyano, halogen, trifluoromethyl, amino, C1 -C7 -alkylamino, di-C1 -C7 -alkylamino and/or by C1 -C7 -alkanoylamino, can be used as the active ingredients of medicaments and are manufactured in a manner known per se.
- -
-
-
- Benzopyrans having an unsaturated side chain
-
3-Formyl-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-1-ol, ethers and esters thereof having the formula STR1 wherein R is hydrogen, lower alkyl or lower alkanoyl and R6 is formyl or 1,3-dithiolan-2-yl but is 1,3-dithiolan-2-yl only when R is hydrogen, and derivatives thereof of the formula STR2 wherein R1 is hydrogen or lower alkanoyl, R2 is alkyl, aryl-lower alkyl or cycloalkyl-lower alkyl, A represents STR3 when R1 is hydrogen and R3 is lower alkyl, and A is STR4 when R1 is lower alkanoyl and R4 is the same lower alkanoyl represented by R1, processes of making such compounds and intermediates useful in such processes, pharmaceutical compositions containing the compounds and the use of the compounds as tranquilizing and antidepressant agents.
- -
-
-