Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Benzyl Compounds”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1994

Percutaneous absorption of benzyl acetate through rat skin in vitro. 3. A comparison with human skin.

The comparative absorption of the fragrance and industrial compound, benzyl acetate, has been studied in rat and human skin, using shaved, full-thickness dorsal skin of male Fischer 344 rats and full-thickness human skin obtained from patients undergoing surgical resection. Penetration of the compound through rat and human skin was evaluated in vitro in flow-through diffusion cells following topical application of neat [methylene-14C] benzyl acetate (33.1 mg/cm2) to the epidermal surface and occlusion with a teflon cap, 2.9 cm above the skin surface. The absorption of benzyl acetate across rat skin was rapid and extensive, reaching 34.3 +/- 3.9% of the applied dose (11.3 +/- 1.3 mg/cm2) (mean +/- SD, n = 12) at 24 hr and 55.8 +/- 5.0% of the applied dose (18.5 +/- 1.7 mg/cm2) at 72 hr. The penetration of benzyl acetate was significantly (P < 0.05) less rapid and extensive through human skin, reaching 5.5 +/- 0.1% of the applied dose (1.8 +/- 0.0 mg/cm2) (mean +/- SD, n = 12) at 24 hr and 17.8 +/- 3.3% of the applied dose (5.9 +/- 1.1 mg/cm2) at 72 hr. The rate of penetration of benzyl acetate was greater through rat skin than through human tissue at all time points studied up to 72 hr. The maximum rate of skin penetration was 0.6 +/- 0.1 mg/cm2/hr and 0.1 +/- 0.0 mg/cm2/hr through rat and human skin, respectively. These data indicate that systemic exposure to benzyl acetate may occur after skin contact in humans. They also support the evidence from the literature that human skin is generally less permeable to xenobiotics than rat skin.

Animals↗
PubMed1999

Probing the "active site" of diamine oxidase: structure-activity relations for histamine potentiation by O-alkylhydroxylamines on colonic epithelium.

The responses of the canine colonic epithelium to histamine are potentiated by O-alkylhydroxylamines. A study of a series of such compounds suggested that active compounds had the structure R-O-NH2, substitution of a nitrogen led to total loss of activity. The locus of the potentiation effect was traced to the inhibition of diamine oxidase. A new series of aliphatic and aromatic O-alkylhydroxylamines were synthesized to explore further the structure-activity relations of this effect. The potentiating effects of these compounds were determined by examining the changes in short circuit current (Isc) produced by histamine and from the activity of a soluble preparation of diamine oxidase. We found that 1) branched compounds are less active than their straight chain counterparts, 2) greater steric bulk of the aliphatic substituent decreased activity, 3) the presence of a double bond had no significant effect though a triple bond reduced activity, 4) longer straight chain compounds were less active than the shorter chain derivatives and 5) all benzylic compounds were less active than the straight chain aliphatics. O-1-benzyl was inactive however the meta or para oxygen substituted compounds as well as the O-(1-E-Cinnamyl) derivative were active. A current model for the action of diamine oxidase proposes a crucial role for a trihydroxyphenylalanine quinone cofactor as part of the active site together with a copper atom. Using molecular modeling based on our inhibition data we are able to define the region of space that is just beyond the reactive carbonyl of the trihydroxyphenylalanine residue at the active site of diamine oxidase. We suggest that a negatively charged species, such as an aspartate or a glutamate, resides in a trough about 7 to 8 A from the trihydroxyphenylalanine carbonyl carbon and this species aids in the strong selective binding of substrates such as putrescine and histamine.

Amine Oxidase (Copper-Containing)↗
PubMed2004

Increased anti-P-glycoprotein activity of baicalein by alkylation on the A ring.

The aqueous extract of Scutellariae baicalensis Georgi has inhibitory activity against P-gp 170, a multiple drug resistant gene product. Baicalein, one of the major flavones, was found to be responsible for this activity. The hydroxyl groups of the A ring of baicalein were systematically alkylated in order to assess the effect of such modifications on the activity against P-gp 170. The impact of the baicalein modifications on activity against the growth of a human nasopharyngeal cancer cell line KB and its P-gp 170 overexpressing cell line KB/MDR were also examined. The results indicate that alkylation of R5 of baicalein does not have a major impact on the interaction with P-gp 170, whereas alkylation of R6 or R7 alone or both, could enhance the interaction of baicalein with P-gp 170 as well as the amount of intracellular accumulation of vinblastine, a surrogate marker for the activity of P-gp 170 pump of KB/MDR cells. In this case, the optimal linear alkyl functionality is a propyl side chain. These modifications could also alter the activity of compounds inhibiting cell growth. Among the different compounds synthesized, the most potent molecule against P-gp 170 is 5-methoxy-6,7-dipropyloxyflavone (23). Its inhibitory activity against P-gp 170 is approximately 40 times better, based on EC50 (concentration of the compound enhancing 50% of the intracellular vinblastine accumulation in the KB/MDR cells) and 3 times higher, based on Amax (the intracellular vinblastine accumulation of the KB/MDR cells caused by the compound) as compared to baicalein. Compound 23 is also a more selective inhibitor than baicalein against P-gp 170, because its cytotoxicity is less than that observed for baicalein. The growth inhibitory IC50 of compound 23 against KB and KB/MDR cells are about the same, suggesting that compound 23 is unlikely to be a substrate of P-gp 170 pump. Acetylation of R6, R7 or both could also decrease EC50 and increase Amax. Acetylated compounds are more toxic than baicalein, and their potency against cell growth is compromised by the presence of P-gp 170, suggesting that these compounds are substrates of P-gp 170. Benzylation of R6 or R7 but not both also enhanced anti-P-gp170 activity and potency against cell growth; however, the presence of P-gp 170 in cells did not have an impact on their sensitivity to these molecules, suggesting that the benzylated compounds are inhibitors but not substrates of P-gp 170, and perhaps have a different mechanism of action. In conclusion, the substitutions of R6 and R7 hydroxyl groups by alkoxy groups, acetoxy groups, or benzyloxy groups could yield compounds with different modes of action against P-gp 170 with different mechanisms of action against cell growth.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Palladium-catalyzed benzylation of active methine compounds without additional base: remarkable effect of 1,5-cyclooctadiene.

[reaction: see text] The palladium complex prepared from DPPF and Cp(eta3-C3H5)Pd is an effective catalyst for the alkylation of active methine compounds with benzylic carbonates under neutral conditions. The addition of 1,5-cyclooctadiene brought about remarkable improvement in the lifetime of the palladium catalyst, which led to high yields of the desired benzylation products.

Journal Article↗
PubMed2003

Synthesis and biological evaluations of pyrazolo[3,4-d]pyrimidines as cyclin-dependent kinase 2 inhibitors.

A series of 1,4,6-trisubstituted pyrazolo[3,4-d]pyrimidines 15-19, 30-38 capable of selectively inhibiting CDK2 activity were synthesized by derivatization at C-4, C-6 and N-1 with various amines and lower alkyl groups. For above synthetic compounds, biological evaluation was carried out and structure-activity relationship was examined. In our series, 4-anilino compounds exhibited better CDK2 inhibitory activity and antitumor activity compared to 4-benzyl compounds. The compounds 33a,b having a 3-fluoroaniline group at C-4 showed comparable or superior CDK2 inhibitory activity to those of olomoucine and roscovitine as reference compounds. In general, the unsubstituted compounds (30a,b, 33a,b, 36a,b) at N-1 possessed higher potency than the substituted compounds (32a,b, 34a,b) for the CDK2 inhibitory activity. As for EGFR inhibitory activity, most compounds didnot have a significant activity. The compounds 32a,b exhibited potent cell growth inhibitory activity against human cancer cell lines, but their CDK2 inhibitory activities were slightly poorer than olomoucine.

Aniline Compounds↗
PubMed1983

Synthesis and biological evaluation of sparsomycin analogues.

Three series of sparsomycin analogues were prepared and examined for their ability to inhibit DNA or protein synthesis in bone marrow, P388 lymphocytic leukemia, and P815 mastocytoma cells. The compounds of series I and II, distinguished by the inclusion or exclusion of a hydroxymethyl functional group, were designed to elucidate the effect on activity of replacing the oxodithioacetal side chain of sparsomycin with 4-substituted benzyl groups. The series III analogues, which excluded the hydroxymethyl group and replaced the oxodithioacetal moiety of sparsomycin with a benzyl amide group, were designed to investigate the potential interaction of an amide oxygen in contrast to the sulfoxide oxygen of sparsomycin. Overall, the bromobenzyl-substituted analogues imparted the greatest inhibitory activity in the protein synthesis assay, while the methoxybenzyl-substituted analogues displayed the least. The methylbenzyl and the unsubstituted benzyl compounds were intermediate in inhibitory potential. The activity in the protein synthesis assay may correspond to the lipophilic and electronic characteristics of the substituents on the benzyl moiety of the analogues. All of the compounds were inactive in the DNA synthesis assay.

Animals↗
PubMed1994

Synthesis of O-[2-acetamido-2-deoxy-6-O-stearoyl- and -6-O-(2-tetradecylhexadecanoyl)-beta-D-glucopyranosyl]-(1-->4)-N- acetylnormuramoyl-L-alpha-aminobutanoyl-D-isoglutamine, lipophilic disaccharide analogues of MDP.

Silver triflate-promoted condensation of 3,4,6-tri-O-acetyl-2-deoxy-2- phthalimido-beta-D-glucopyranosyl bromide (1) with benzyl 2-acetamido-6-O-benzyl-2-deoxy-3-O- (methoxycarbonyl)methyl-alpha-D-glucopyranoside (4) afforded the key compound, benzyl 2-acetamido-6-O-benzyl-2-deoxy-3-O- (methoxy-carbonyl)methyl-4-O-(3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-b eta-D- glucopyranosyl)-alpha-D-glucopyranoside (5), which after deprotection was transformed into acid 10. Condensation of 10 with the benzyl ester of L-alpha-aminobutanoyl-D-isoglutamine and deisopropylidenation of the product 11 afforded the benzyl ester of N-(2-O-[benzyl 2-acetamido-4-O-(2-acetamido-3-O-benzyloxymethyl-2- deoxy-beta-D-glucopyranosyl)-6-O-benzyl-2,3-dideoxy-alpha-D-glucopyra nosid-3- yl]glycoloyl)-L-alpha-aminobutanoyl-D-isoglutamine (12). Partial O-acylation of 12 and hydrogenolysis of protecting groups gave the 6-O-stearoyl- and 6-O-(2-tetradecylhexadecanoyl)-disaccharide-dipeptides 17 and 18, respectively. Pyrogenicity and adjuvant activity in cell-mediated immunity are reported.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

2,4-Dichlorobenzyl thiocyanate, an antimitotic agent that alters microtubule morphology.

A compound of simple structure, 2,4-dichlorobenzyl thiocyanate (DCBT), is an antimitotic agent with a number of unusual properties. The drug causes an extreme reorganization of microtubules in cells in culture. Most normal microtubules disappear, and remaining tubulin-containing structures appear to be bundled or aggregated. DCBT irreversibly inhibits in vitro polymerization of purified tubulin, but only after a prolonged preincubation of the protein with the drug. Binding of radiolabeled DCBT to tubulin similarly requires a long incubation time, with the reaction not being complete even after 6 hr at 37 degrees C. A specific interaction with tubulin is also shown by the crossresistance to DCBT of Colcemid-resistant cells with an altered beta-tubulin. A human KB carcinoma cell line and a Chinese hamster ovary cell line selected for crossresistance to multiple chemotherapeutic agents, including most antimitotic drugs, are sensitive to DCBT. Initial structure-function studies have demonstrated weak antimitotic and antitubulin activity with the parent compound benzyl thiocyanate. Chlorination at either position 2 or position 4 of the phenyl ring produces compounds of intermediate activity (4-chlorobenzyl thiocyanate is more active than 2-chlorobenzyl thiocyanate). The thiocyanate moiety appears to be essential for activity.

Cell Line↗
PubMed2001

Involvement of the mitochondrial death pathway in chemopreventive benzyl isothiocyanate-induced apoptosis.

In the present study, we studied the molecular mechanism underlying cell death induced by a cancer chemoprotective compound benzyl isothiocyanate (BITC). The cytotoxic effect of BITC was examined in rat liver epithelial RL34 cells. Apoptosis was induced when the cells were treated with 20 mum BITC, characterized by the appearance of phosphatidylserine on the outer surface of the plasma membrane and caspase-3 activation, whereas no caspase activation and propidium iodide incorporation into cell were detected with 50 mum BITC that induced necrosis. The mitochondrial death pathway was suggested to be involved in BITC-induced apoptosis because the treatment of cells with BITC-induced caspase-9-dependent apoptosis and mitochondrial transmembrane potential (Delta Psi m) alteration. We demonstrated here for the first time that BITC directly modifies mitochondrial functions, including inhibition of respiration, mitochondrial swelling, and release of cytochrome c. Moreover, glutathione depletion by diethyl maleate significantly accelerated BITC-triggered apoptosis, suggesting the involvement of a redox-dependent mechanism. This was also implicated by the observations that intracellular accumulation of reactive oxygen species, including superoxide (O(2)) and hydroperoxides (HPOs), was indeed detected in the cells treated with BITC and that the intracellular HPO level was significantly attenuated by pretreatment with N-acetylcysteine. The treatment with a pharmacological scavenger of O(2), Tiron, also diminished the HPO formation by approximately 80%, suggesting that most of the HPOs were H(2)O(2) derived from the dismutation of O(2). These results suggest that BITC induces apoptosis through a mitochondrial redox-sensitive mechanism.

Animals↗
PubMed2001

Diastereoselective ruthenium-Cp complexation of enantiopure arene compounds possessing stereogenic benzylic alcohol functionalities.

[reaction--see text] Enantiopure (arene)ruthenium compounds possessing a stereogenic benzylic alcohol functionality were stereoselectively synthesized by diastereoselective ruthenium-Cp complexation to a distinct arene face. This diastereoselective ruthenium-Cp complexation was further extended to biaryl compounds linked with a six-membered lactone bridge for the synthesis of enantiomerically pure, axially chiral biaryls.

Journal Article↗
PubMed2002

Synthesis and calcium channel antagonist activity of new 1,4-dihydropyridine derivatives containing dichloroimidazolyl substituents.

A group of dialkyl, dicycloalkyl and diaryl ester analogues of nifedipine (CAS 21829-25-4), in which the ortho-nitrophenyl group at position 4 is replaced by a 4,5-dichloroimidazolyl substituent, were synthesized and evaluated as calcium channel antagonists using the high K+ contraction of guinea-pig ileal longitudinal smooth muscle. The results for the symmetrical esters in alkyl esters series showed that increasing the length of the methylene chain in C3 and C5 ester substituents (from n = 0 to n = 2) increased the activity. When increasing of the length was accompanied by increase of the hindrance, the activity decreased. In the unsymmetrical diester series, the results showed when R1 is a small substituent (R1 = Me), increasing of the lipophilic property in R2 substituent increases the activity if this high lipophilicity is not accompanied by steric hindrance. The results demonstrate that in the unsymmetrical series, several compounds (benzyl methyl, benzyl isopropyl and cyclohexyl ethyl) had activity similar to that of the reference drug nifedipine. In symmetrical diesters compounds, the most active compound was the diphenethyl ester derivative being more active than nifedipine. These structure-activity data indicate that the 4-(4,5-dichloroimidazolyl) moiety is the bioisoester of 3-nitrophenyl and 2,3-dichlorophenyl moieties.

Animals↗
PubMed1975

Chemical Basis for Greenbug Resistance in Small Grains: II. Identification of the Major Neutral Metabolite of Benzyl Alcohol in Barley.

((14)C)Benzyl alcohol was administered either by uptake through the roots or by injection directly into the stems of wheat (Triticum aestivum L. em Thell), sorghum (Sorghum bicolor. L Moench) and two strains of barley (Hordeum vulgare L.). One strain of barley was susceptible to the greenbug (Schizaphis granium Rondani), and the other was greenbug-resistant. In all four plants, several radioactive metabolites were formed. The major neutral metabolite has been identified as benzyl-beta-d-glucopyranoside. This glucoside was found to have no biological activity against the greenbug under conditions in which the parent compound, benzyl alcohol, inhibits the reproduction of this insect pest.

Journal Article↗
PubMed1976

Inhibition of separated forms of phosphodiesterases from pig coronary arteries by uracils and by 7-substituted derivatives of 1-methyl-3-isobutylxanthine.

A series of 7-substituted 1-methyl-3-isobutylxanthines was designed in an attempt to increade the specificity of the 1-methyl-3-isobutylxanthine (MIX) structure for one of the two cyclic nucleotide phosphodiesterase peaks isolated by DEAE-cellulose chromatography of the soluble fraction of the intima + media layer of pig coronary arteries. A series of 1,3-dialkyluracils was of low potency as inhibitors of either peak I or peak II. The 7-substituted xanthines were prepared by alkylation of MIX with the corresponding alkyl or aralkyl halide in DMF containing K2CO3. These compounds were, in general, much less potent inhibitors of peak II activity than was MIX, but some of them retained the potency of MIX as inhibitors of peak I and, therefore, were relatively specific for inhibition of peak I. 7-Bzl-MIX was the most selective compound tested; it was a potent inhibitor of peak I activity but was much less effective as an inhibitor of peak II activity. Substitution of either electron-withdrawing (nitro) or electron-donating (methoxy) groups on the 7-benzyl moiety reduced the effectiveness of the 7-benzyl compounds as inhibitors of peak I. Chlorobenzyl substitution increased the potency slightly over the benzyl but not the selectivity between peaks.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2003

Benzothiadiazine dioxide human cytomegalovirus inhibitors: synthesis and antiviral evaluation of main heterocycle modified derivatives.

The benzothiadiazine dioxide derivatives are potent non-nucleoside human cytomegalovirus (HCMV) inhibitors. As part of our comprehensive structure-activity relationship (SAR) study of these compounds, we have now proposed structural modifications on the heterocyclic moiety both on the number and the nature of the fused heterocycle and on the kind of heteroatoms present on it. Synthesis of these new compounds (benzyl derivatives of thiadiazines, thienothiadiazines, benzothienothiadiazines and quinazolines) and the antiviral evaluation against HCMV has been performed. SAR investigation on this class of compounds has defined the structural requirements for potency and toxicity. They have revealed two important clues: i) a fused ring to the thiadiazine framework is necessary to maintain the anti-HCMV action, and ii) the sulfamido moiety in the main heterocycle is crucial to avoid cytotoxicity.

Antiviral Agents↗
PubMed1982

Inhibition of rat liver cytochrome P-450 by benzyl hydrodisulfide.

The inhibition of rat liver microsomal cytochrome P-450 by benzyl hydrodisulfide has been examined as a model system for the inactivation of cytochrome P-450 seen during the microsomal metabolism of thiono-sulfur-containing compounds. Benzyl hydrodisulfide decreased enzymatic activity toward benzphetamine when incubated with hepatic microsomes prior to the assay for monooxygenase activity. In addition, incubation of microsomes with the hydrodisulfide caused a decrease in the level of cytochrome P-450 detectable as its carbon monoxide complex as well as a decrease in heme detectable as its pyridine-hemochromogen. In a typical experiment, the loss of enzymatic activity, cytochrome P-450, and heme were 65, 56, and 51%, respectively. These data suggest that the major loss of monooxygenase activity and of cytochrome P-450 which was seen on incubation of microsomes with benzyl hydrodisulfide results from an alteration in the structure of the heme moiety of cytochrome P-450. A similar alteration in the heme moiety of cytochrome P-450 is believed to be responsible, in part, for the loss of monooxygenase activity and cytochrome P-450 seen on incubation of parathion and other thiono-sulfur-containing compounds with hepatic microsomes or a reconstituted cytochrome P-450-containing monooxygenase system.

Animals↗
PubMed1998

Evaluation of benzyl selenocyanate glutathione conjugate for potential chemopreventive properties in colon carcinogenesis.

Observational, clinical and experimental studies have suggested that dietary supplementation with selenium can inhibit the development of colon cancer. Since toxicity and chemopreventive efficacy of selenium compounds depend to a large extent, on the form of selenium the development of efficacious organoselenium compounds with low toxicity is being pursued in our laboratory. We have assessed the chemopreventive properties of a newly synthesized organoselenium compound, benzyl selenocyanate glutathione conjugate (BSeSG), and of benzyl selenocyanate (BSC), as a positive control, using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) as a measure of efficacy. Five-week-old male F344 rats were fed the control diet (modified AIN-76A) or experimental diets containing 10 or 20 ppm BSeSG (1.7 and 3.4 ppm as Se, respectively), or 10 ppm BSC (4.1 ppm as Se). One week later, all animals except those in vehicle (normal saline)-treated groups were s.c. injected with AOM (15 mg/kg of body weight, once weekly for 2 weeks). All animals were sacrificed 7 weeks after the last AOM injection, and the ACF, levels of prostaglandin E2 (PGE2), cyclooxygenase protein expression (COX-1 and -2), and glutathione S-transferase type mu (GST-mu) were determined in the colon. As expected, dietary administration of BSC suppressed ACF development by about 37%. In rats administered 10 or 20 ppm BSeSG, the frequencies of AOM-induced colonic ACF were significantly decreased compared to those of rats given AOM and control diet by about 41% (P<0.01) and 61% (P<0.001), respectively. Administration of BSeSG inhibited PGE2 production (81-88% inhibition) via COX-2 synthesis in the colonic mucosa (18-60% inhibition). Also, BSeSG increased GST-mu protein activity in colonic mucosa (30-32% increase). These data suggest that a newly synthesized organoselenium compound, BSeSG might be a promising chemopreventive agent against colon carcinogenesis.

Animals↗
PubMed1991

Radioiodination and biodistribution of analogs of a calichemicin constituent.

Analogs of the aromatic constituent of calichemicins were labeled with 131I by exchange reactions. Radiochemical yield for methyl-4-hydroxy-5-iodo-2,3-dimethoxy-6-methylbenzoate was approx. 90%. For methyl-4-benzyloxy-2-hydroxy-3-iodo-6-methylbenzoate the yield was about 30%. Biodistribution studies were carried out in mice following intravenous administration of tracer doses. Average brain uptake of the first compound at 3 min was 0.28%, and that of the second 1.96%. Tissue distribution of the two compounds elsewhere was similar in nature. High uptake was observed initially in the liver; this reduced with time, while radioactivity in the GI-tract increased. The benzylated compound appeared potentially useful for designing a brain imaging radiopharmaceutical.

Animals↗