Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LACTONES”

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 181 records · Page 10Linked to original sources
PubMed2006

Pharmacokinetics of lactone, carboxylate and total 9-nitrocamptothecin with different doses and administration routes in rats.

9-Nitrocamptothecin (9-NC) is a newly developed poorly soluble derivative of camptothecin and has a wide spectrum of anticancer activity in preclinical evaluation. The effects of the dose and administration route on pharmacokinetics and lactone/carboxylate equilibrium of 9-NC were studied in rats. A single intravenous dose of 1.5, 3 or 6 mg/kg of 9-NC solution was given to male rats (n = 6 per dose level). In another study, a single dose of 6 mg/kg 9-NC solution was given orally to rats (n = 6). Plasma samples were drawn at predetermined intervals and the concentrations of lactone, carboxylate and total 9-NC were determined by a validated HPLC method. Pharmacokinetic analysis was performed using non-compartmental analysis. Analysis of variance showed that the pharmacokinetic characteristics of lactone, carboxylate and total 9-NC were all independent of dose (p > 0.05). Based on the AUC measurements, the lactone 9-NC constituted 52% +/- 4%, 49% +/- 6% and 55% +/- 6% of the circulating total 9-NC in rats after intravenous administration of 1.5, 3, 6 mg/kg 9-NC solution, respectively. After oral administration of 6 mg/kg, the pharmacokinetics parameters were significantly different from those of intravenous administration at the same dose (p < 0.05). The lactone ratio was 60% +/- 14%. The absolute bioavailability of lactone and total 9-NC were calculated to be 23.4% and 22.7%, respectively. In conclusion, the pharmacokinetics of lactone, carboxylate and total 9-NC are not dose-dependent. Lactone, carboxylate and total 9-NC are poorly absorbed following oral administration. Both the dose and the route of administration have little effect on the lactone/carboxylate equilibrium of 9-NC in rats in vivo. But the route of administration plays an important part on the pharmacokinetics of 9-NC.

Administration, Oral↗
PubMed1995

High-performance liquid chromatographic analysis of the lactone and carboxylate forms of a topoisomerase I inhibitor (the antitumor drug GI147211) in plasma.

A sensitive reversed-phase high-performance liquid chromatographic method has been developed and validated for the quantitation of the lactone form (GI147211) of a topoisomerase I inhibitor and its carboxylate form (GI190421) from dog plasma. The method consists of two solid-phase extraction methods. The first method, referred to as the lactone-only method, utilizes a diol Bond Elut cartridge to separate the two forms and measures the lactone directly. The second method, referred to as the total method, converts the carboxylate form to the lactone through acidification of the plasma sample. Total lactone is then extracted from the sample using a C18 Bond Elut cartridge. The carboxylate is quantitated indirectly from the difference of the total and lactone-only. The range of the standard curve for the lactone-only method is 0.096-38.5 nM (0.05-20 ng/ml) and for the total method is 0.193-19.3 nM (0.1-10 ng/ml). This is the most sensitive method reported to date for a camptothecin analogue.

Animals↗
PubMed2005

Simultaneous determination of the lactone and carboxylate forms of irinotecan (CPT-11) and its active metabolite SN-38 by high-performance liquid chromatography: application to plasma pharmacokinetic studies in the rat.

Irinotecan (CPT-11) and its main metabolite SN-38 are potent anticancer derivatives of camptothecin (CPT), with active lactone and inactive carboxylate forms coexisting. A simple and sensitive HPLC method using the ion-pairing reagent tetrabutylammonium hydrogen sulfate (TBAHS) was developed to simultaneously determine all four analytes in rat plasma samples. Camptothecin (CPT) was used as internal standard. The mobile phase was 0.1M potassium dihydrogen phosphate containing 0.01 M TBAHS (pH 6.4)-acetonitrile (75:25, v/v). Separation of the compounds was carried out on a Hypersil C18 column, monitored at 540 nm (excitation wavelength at 380 nm). All four compounds gave linear response as a function of concentration over 0.01-10 microM. The limit of quantitation in rat plasma was 0.01, 0.008, 0.005 and 0.005 microM for CPT-11 lactone, CPT-11 carboxylate, SN-38 lactone and SN-38 carboxylate, respectively. The method was successfully used in the study on the effect of coadministered thalidomide on the plasma pharmacokinetics of CPT-11 and SN-38 in rats. Coadministered thalidomide (100mg/kg body weight by intraperitoneal injection) significantly increased the AUC(0-10h) values of CPT-11 lactone and CPT-11 carboxylate by 32.6% and 30.3 %, respectively, (P < 0.01), but decreased the values by 19.2% and 32.4% for SN-38 lactone and carboxylate, respectively, (P < 0.05). Accordingly, the value of total body clearance (CL) of CPT-11 lactone was significantly lower in combination group compared to the control (1.329 versus 1.837 L/h/kg, P = 0.0002). Plasma t(1/2beta) values for SN-38 lactone and carboxylate were significantly (P < 0.01) smaller in rats with coadministered thalidomide, as compared to rats receiving CPT-11 alone. Further studies are needed to explore the underlying mechanisms for the observed kinetic interaction between CPT-11 and thalidomide.

Animals↗
PubMed2000

Structural requirements of sesquiterpene lactones to inhibit LPS-induced nitric oxide synthesis in RAW 264.7 macrophages.

Some sesquiterpene lactones were recently demonstrated to inhibit inducible nitric oxide synthase (iNOS)-dependent nitric oxide (NO) synthesis. The primary objective of the present study was, therefore, to find evidence for structural requirements of sesquiterpene lactones regarding their capability to inhibit iNOS-dependent NO synthesis. Sesquiterpene lactones 1-11 were examined for their influence on nitrite accumulation in cell culture supernatants of LPS-induced RAW 264.7 macrophages. Except the taraxinic acid beta-D-glucopyranosylester 8 all compounds showed a dose-dependent inhibition of nitrite accumulation in cell culture supernatants with IC50 values ranging from 0.5 to 36.8 microM. High activity seemed to be dependent on an alpha-methylene-gammalactone functionality. Cytotoxicity and the ability to inhibit activation of transcription factor NF-kappaB are further biological activities of sesquiterpene lactones. The second point of interest was, therefore, whether the structural requirements of sesquiterpene lactones for these activities may differ or be the same for those needed to inhibit iNOS-dependent NO synthesis. Using concentrations of 1-11 required to inhibit NO synthesis cell viability was determined and NF-kappaB binding activity was measured by gel-shift experiments. Interestingly, compounds almost equally effective in inhibiting nitrite accumulation did not show the same cytotoxic potential, and most sesquiterpene lactones inhibited nitrite accumulation at concentrations where inhibition of NF-kappaB activation was not significant. These results suggest that different biological activities of sesquiterpene lactones have different structural requirements.

Animals↗
PubMed1987

Kinetics and mechanism of human leukocyte elastase inactivation by ynenol lactones.

Human leukocyte elastase (HLE), a serine protease involved in inflammation and tissue degradation, can be irreversibly inactivated in a time- and concentration-dependent manner by ynenol lactones. Ynenol lactones that are alpha-unsubstituted do not inactivate but are alternate substrate inhibitors that are hydrolyzed by the enzyme. Ynenol lactones that are both substituted alpha to to the lactone carbonyl and unsubstituted at the acetylene terminus are rapid inactivators of HLE and inactivate pancreatic elastase and trypsin more slowly. 3-Benzyl-5(E)-(prop-2-ynylidene)tetrahydro-2-furanone inactivates HLE with biphasic kinetics and an apparent second-order rate of up to 22,000 M-1 s-1 (pH 7.8, 25 degrees C). The rate of inactivation is pH-dependent and is slowed by a competitive inhibitor. The partition ratio is 1.6 +/- 0.1. Rapid removal of ynenol lactone during the course of inactivation yields a mixture of acyl and inactivated enzyme species, which then shows a partial recovery of activity that is time- and pH-dependent. Inactivation is not reversible with hydroxylamine. The enzyme is not inactivated if the untethered allenone is added exogenously. All of these results are consistent with a mechanism involving enzyme acylation at serine-195 by the ynenol lactone, isomerization of the acyl enzyme to give a tethered allenone, and capture of a nucleophile (probably histidine-57) to inactivate the enzyme. Substitution at the acetylene terminus of ynenol lactones severely reduces their ability to inactivate HLE, because allenone formation is slowed and/or nucleophile capture is hindered. Chemical competence of each of these steps has been demonstrated [Spencer, R.W., Tam, T.F., Thomas, E.M., Robinson, V.J.,& Krantz, A. (1986) J. Am. Chem. Soc. 108, 5589-5597].

Alkynes↗
PubMed1987

Strong inhibitory effect of furanoses and sugar lactones on beta-galactosidase Escherichia coli.

Various sugars and their lactones were tested for their inhibition of beta-galactosidase (Escherichia coli). L-Ribose, which in the furanose form has a hydroxyl configuration similar to that of D-galactose at positions equivalent to the 3- and 4-positions of D-galactose, was a very strong inhibitor, and D-lyxose, which in the furanose form also resembles D-galactose, was a much better inhibitor than expected. Structural comparisons prelude the pyranose forms of these sugars from being significant contributors to the inhibition, and inhibition at different temperatures (at which there are different furanose concentrations) strongly supported the conclusion that the furanose form is inhibitory. Studies with sugar derivatives that can only be in the furanose form also supported the conclusion. This is the first report of the inhibitory effect of furanose on beta-galactosidase. Lactones were also inhibitory. Every lactone tested was much more inhibitory than was its parent sugar. D-Galactonolactone was especially good. Experiments indicated that it was D-galactono-1,5-lactone rather than D-galactono-1,4-lactone which was inhibitory. Inhibition of beta-galactosidases from mammalian sources by lactones has been reported previously, but this is the first report of the effect of beta-galactosidase from E. coli. Since furanoses in the envelope form are analogous (in some ways) to half-chair or sofa conformations and since lactones with six-membered rings probably have half-chair or sofa conformations, the results indicate that beta-galactosidase probably destabilizes its substrate into a planar conformation of some type and that the galactose in the transition state may, therefore, also be quite planar.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate Conformation↗
PubMed2000

Synthesis and biological activity of alpha-methylene-gamma-lactones as new aroma chemicals.

Seven kinds of alpha-methylene-gamma-lactones with an alkyl group at the C-4 position were synthesized according to a previously described method, with yields of 28-34%. These alpha-methylene-gamma-lactones had characteristic and unique odors. All alpha-methylene-gamma-lactones added a roast-like odor to materials. The antimicrobial effects of alpha-methylene-gamma-lactones were investigated by using a paper disk diffusion method. The results showed the alpha-methylene-gamma-lactones inhibited the growth of three bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas fluorescens) and two fungi (Saccharomyces cerevisiae and Aspergillus niger). In particular, alpha-methylene-gamma-undecalactone and alpha-methylene-gamma-dodecalactone exhibited potent inhibition of the growth of these microorganisms compared to butyl p-hydroxybenzoate as standard antibiotic. The umu test revealed that the alpha-methylene-gamma-lactones suppressed the SOS-inducing activity of three mutagens, furylfuramide, UV irradiation, and Trp-P-1, respectively. The antimicrobial effects and the suppressive effects of SOS induction by alpha-methylene-gamma-lactones had a tendency to intensify as the number of carbons in the side chain increased.

Alkanes↗
PubMed2001

Evidence of starch inclusion complexation with lactones.

Starch, in particular the linear amylose, is able to form inclusion complexes with a wide spectrum of ligand molecules, among them flavor compounds. The complexing ability of a homologous series of gamma- and delta-lactones with potato starch was followed by amperometric iodine titration, differential scanning calorimetry, and wide-angle X-ray diffraction measurements. Lactones with a linear chain of a size > or = C(5) form inclusion complexes with starch, whereas lactones with a short linear chain, such as gamma-heptalactone, show poor complexing ability. The thermal stability of starch-lactone complexes increases with increasing chain length of the lactone. In general, lactones induce the formation of V(h) helices. Only delta-decalactone complexes with starch were not definitely identified as V(h) amylose helices. Complexation of starch dispersions with lactones induce turbidity and gelation or phase separation, both phenomena being the result of microphase separation.

Amylose↗
PubMed1995

Steroidal spiro-gamma-lactones that inhibit 17 beta-hydroxysteroid dehydrogenase activity in human placental microsomes.

The important enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) is known to regulate intracellular levels of biologically active steroids, namely, androgens and estrogens. In an effort to develop potent inhibitors of 17 beta-HSD for reducing the levels of active steroids, we found that steroidal spiro-gamma-lactones inhibit 17 beta-HSD activity. In this report, we describe the synthesis of 11 spiro-gamma-lactone analogs containing a steroidal C-18 or C-19 nucleus and compare their relative inhibitory effects on 17 beta-HSD activity in the human placenta microsomes that catalyze the interconversion of androgens and estrogens. To void the interaction of the cytosolic 17 beta-HSD activity that is specific for the interconversion of estrone and estradiol, we used 4-androstenedione as substrate. Analysis of the inhibitory effect exerted by these analogs on microsomal 17 beta-HSD activity indicates that spiro-gamma-lactones containing the C-18 nucleus are more potent inhibitors than C-19 nucleus analogs. The best inhibition was obtained with the phenolic spiro-gamma-lactone 7 (3-hydroxy-19-nor-17 alpha-pregna-1,3,5(10)-triene 21,17-carbolactone), which has an IC50 value of 0.27 microM, and was much lower than the competitive effect of the unlabeled substrate 4-androstenedione, which has an IC50 value of 1.40 microM. Preincubation with lactone 7 did not inactivate 17 beta-HSD activity. The results thus suggest that lactone 7 is a reversible in inhibitor. Lactone 7 is selective for microsomal 17 beta-HSD activity, as no inhibition was observed for cytosolic 17 beta-HSD activity.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

Bicyclic lactones derived from kainic acid as novel selective antagonists of neuroexcitatory amino acids.

The bicyclic [2S-(2 alpha,3 beta,4 beta)]-2-carboxy-4-(1-hydroxy-1-methylethyl)-3- pyrrolidineacetic acid delta-lactone (4), as well as its 4-[1-hydroxy-1-(iodomethyl)ethyl], 4-[1-hydroxy-1-(hydroxymethyl)ethyl], and 4-[1-hydroxy-1-[(phenyl-thio)methyl]ethyl] analogues, 6, 7, and 9, respectively, were designed and synthesized as potential selective antagonists of neuroexcitatory amino acids. When applied to rat brain slices, these lactones, which are chemically derived from kainic acid, inhibit the stimulation of Na+ fluxes induced by the neuroexcitants kainic acid and N-methyl-D-aspartic acid. Lactone 4 and the hydroxy lactone 7 block preferentially the response to N-methyl-D-aspartic acid, while the iodo lactone 6 and the phenylthio lactone 9 are mainly kainic acid antagonists. Total inhibitions can be obtained, half of the maximal effect being observed at lactone concentrations in the range of 0.2-3 mM.

Amino Acids↗
PubMed2006

Conformationally constrained analogues of diacylglycerol. 26. Exploring the chemical space surrounding the C1 domain of protein kinase C with DAG-lactones containing aryl groups at the sn-1 and sn-2 positions.

Diacylglycerol lactones (DAG-lactones) are known to operate as effective agonists of protein kinase C (PKC), surpassing in potency the activity of natural diacylglycerol (DAG). Localization of activated PKC isozymes in the cell is determined in part by the different cellular scaffolds, the lipid composition of the specific membranes, and the targeting information intrinsic to the individual isoforms bound to DAG. This multifaceted control of diversity suggests that, to develop effective DAG-lactones capable of honing in on a specific cellular target, we need to gain a better understanding of the chemical space surrounding its binding site. Seeking to augment the chemical repertoire of DAG-lactone side chains that could steer the translocation of PKC to specific cellular domains, we report herein the effects of incorporating simple or substituted phenyl residues. A combined series of n-alkyl and phenyl substitutions were used to explore the optimal location of the phenyl group on the side chains. The substantial differences in binding affinity between DAG-lactones with identical functionalized phenyl groups at either the sn-1 or sn-2 position are consistent with the proposed binding model in which the DAG-lactone binds to the C1 domain of PKC with the acyl chain oriented toward the interior of the membrane and the alpha-alkylidene or alpha-arylalkylidene chains directed to the surface of the C1 domain adjacent to the lipid interface. We conclude that DAG-lactones containing alpha-phenylalkylidene side chains at the sn-2 position represent excellent scaffolds upon which to explore further chemical diversity.

Diglycerides↗
PubMed2000

Conformationally constrained analogues of diacylglycerol (DAG). 17. Contrast between sn-1 and sn-2 DAG lactones in binding to protein kinase C.

In previous work, we have obtained potent protein kinase C (PK-C) ligands with low-namomolar binding affinities by constructing diacylglycerol (DAG) mimetics in which the sn-2 carbonyl of DAG was constrained into a lactone ring. An additional structural element that helped achieve high binding affinity was the presence of branched acyl or alpha-alkylidene chains. In the present study, the effects of similarly branched chains on a different lactone system, where the lactone carbonyl is now equivalent to the sn-1 carbonyl of DAG, are investigated. In this new lactone template, the two chiral centers must have the S-configuration for enzyme recognition. As with the sn-2 DAG lactones, the branched chains were designed to optimize van der Waals contacts with a group of conserved hydrophobic amino acids located on the rim of the C1 domain of PK-C. The acyl and alpha-alkylidene chains were also designed to be lipophilically equivalent (8 carbons each). Eight new compounds (7-14) representing all possible combinations of linear and branched acyl and alpha-alkylidene were synthesized and evaluated. The sn-1 DAG lactones were less effective as PK-C ligands than the sn-2 DAG lactones despite having a similar array of linear or branched acyl and alpha-alkylidene chains

Diglycerides↗
PubMed2006

Practical, catalytic, asymmetric synthesis of beta-lactones via a sequential ketene dimerization/hydrogenation process: inhibitors of the thioesterase domain of fatty acid synthase.

The recent finding that the FDA-approved antiobesity agent orlistat (tetrahydrolipstatin, Xenical) is a potent inhibitor of the thioesterase domain of fatty acid synthase (FAS) led us to develop a concise and practical asymmetric route to pseudosymmetric 3,4-dialkyl-cis-beta-lactones. The well-documented up-regulation of FAS in cancer cells makes this enzyme complex an interesting therapeutic target for cancer. The described route to 3,4-dialkyl-beta-lactones is based on a two-step process involving Calter's catalytic, asymmetric ketene dimerization of acid chlorides followed by a facial-selective hydrogenation leading to cis-substituted-beta-lactones. Importantly, the ketene dimer intermediates were found to be stable to flash chromatography, enabling opportunities for subsequent transformations of these optically active, reactive intermediates. Subsequent alpha-epimerization and alpha-alkylation or acylation led to trans-beta-lactones and beta-lactones bearing alpha-quaternary carbons, respectively. Several of the ketene dimers and beta-lactones displayed antagonistic activity (apparent Ki in the low micromolar range) in competition with a fluorogenic substrate toward a recombinant form of the thioesterase domain of fatty acid synthase. The best antagonist, a simple phenyl-substituted cis-beta-lactone 3d, displayed an apparent Ki (2.5 +/- 0.5 microM) of only approximately 10-fold lower than that of orlistat (0.28 +/- 0.06 microM). In addition, mechanistic studies of the ketene dimerization process by ReactionView infrared spectroscopy support previous findings that ketene formation is rate determining.

Alkenes↗
PubMed2000

Trapping phosphodiester-quinone methide adducts through in situ lactonization.

The goal of in situ modification of DNA via phosphodiester alkylation has led to our design of quinone methide derivatives capable of alkylating dialkyl phosphates. A series of catechol derivatives were investigated to trap the phosphodiester-quinone methide alkylation adduct through in situ lactonization. The catechol derivatives were uniquely capable of characterizable p-quinone methide formation for mechanistic clarity. These investigations revealed that with a highly reactive lactonization group (phenyl ester), lactonization competed with quinone methide formation. Lactone-forming groups of lower reactivity (methyl ester, n-propyl ester, and dimethyl amide) allowed quinone methide formation followed by phosphodiester alkylation; however, they were ineffective at in situ lactonization to drain the phosphodiester alkylation equilibrium to the desired phosphotriester product. The derivatives tethered with lactone-forming functionality of intermediate reactivity (chloro-, trichloro-, and trifluoroethyl esters), allowed quinone methide formation, phosphodiester alkylation, and in situ lactonization to efficiently afford the trapped phosphotriester adduct.

Alkylating Agents↗
PubMed2003

Hydrolysis, lactonization, and identification of alpha(2 --> 8)/alpha(2 --> 9) alternatively linked tri-, tetra-, and polysialic acids.

Alpha-(2 --> 8)/alpha(2 --> 9) alternatively linked polysialic acid (PSA) can be identified by controlled hydrolysis followed by the analysis with capillary electrophoresis (CE). Due to the different stability of alpha(2 --> 8) and alpha(2 --> 9) linkages in acidic hydrolysis, oligosialic acids (OSAs) from the hydrolysis of alpha(2 --> 8)/alpha(2 --> 9) OSA/PSA could be classified into two groups in the CE profile. The group with an odd numerical degree of polymerization (DP) had two peaks in the CE profile, and the other group, with even number of DP, showed one peak. Each alternating alpha(2 --> 8)/alpha(2 --> 9) linked OSA contains two isomers: one starts with the alpha(2 --> 8) linkage from the nonreducing end and the other starts with the alpha(2 --> 9) linkage from the nonreducing end. Trimers and tetramers were isolated by using a Mono Q column with an HPLC system. The two trimer isomers are alpha(2 --> 8)/alpha(2 --> 9) and alpha(2 --> 9)/alpha(2 --> 8) linkages and only showed partial separation by CE. After lactonization, sialidase hydrolysis, and alkaline treatment, the two trimer isomers could be separated and identified by CE analysis, but only the alpha(2 --> 8)/alpha(2 --> 9) trimer could be converted to the dilactone in glacial acetic acid. The two tetramer isomers could be converted to four monolactones and three dilactones. These lactonized species could be identified on the basis of several principles in sialidase hydrolysis and lactonization. In conclusion, regioselectivity on the lactonization of oligosialic acids proceeds under several principles: (1) Lactonization takes place more easily in the alpha(2 --> 8) linkage than in the alpha(2 --> 9) linkage; (2) all of the positions of alpha(2 --> 8) linkages in alpha(2 --> 8)/alpha(2 --> 9) alternatively linked OSA can be lactonized regardless of external or internal carboxyl groups involved; and (3) for the site of alpha(2 --> 9) linkage, only internal carboxyl groups can be lactonized.

Acetic Acid↗
PubMed1994

Multiple N-acyl-L-homoserine lactone autoinducers of luminescence in the marine symbiotic bacterium Vibrio fischeri.

In Vibrio fischeri, the synthesis of N-3-oxohexanoyl-L-homoserine lactone, the autoinducer for population density-responsive induction of the luminescence operon (the lux operon, luxICDABEG), is dependent on the autoinducer synthase gene luxI. Gene replacement mutants of V. fischeri defective in luxI, which had been expected to produce no autoinducer, nonetheless exhibited lux operon transcriptional activation. Mutants released into the medium a compound that, like N-3-oxohexanoyl-L-homoserine lactone, activated expression of the lux system in a dose-dependent manner and was both extractable with ethyl acetate and labile to base. The luxI-independent compound, also like N-3-oxohexanoyl-L-homoserine lactone, was produced by V. fischeri cells in a regulated, population density-responsive manner and required the transcriptional activator LuxR for activity in the lux system. The luxI-independent compound was identified as N-octanoyl-L-homoserine lactone by coelution with the synthetic compound in reversed-phase high-pressure liquid chromatography, by derivatization treatment with 2,4-dinitrophenylhydrazine, by mass spectrometry, and by nuclear magnetic resonance spectroscopy. A locus, ain, necessary and sufficient for Escherichia coli to synthesize N-octanoyl-L-homoserine lactone was cloned from the V. fischeri genome and found to be distinct from luxI by restriction mapping and Southern hybridization. N-Octanoyl-L-homoserine lactone and ain constitute a second, novel autoinduction system for population density-responsive signalling and regulation of lux gene expression, and possibly other genes, in V. fischeri. A third V. fischeri autoinducer, N-hexanoyl-L-homoserine lactone, dependent on luxI for its synthesis, was also identified. The presence of multiple chemically and genetically distinct but cross-acting autoinduction systems in V. fischeri indicates unexpected complexity for autoinduction as a regulatory mechanism in this bacterium.

4-Butyrolactone↗
PubMed1999

Acylhomoserine lactone synthase activity of the Vibrio fischeri AinS protein.

Acylhomoserine lactones, which serve as quorum-sensing signals in gram-negative bacteria, are produced by members of the LuxI family of synthases. LuxI is a Vibrio fischeri enzyme that catalyzes the synthesis of N-(3-oxohexanoyl)-L-homoserine lactone from an acyl-acyl carrier protein and S-adenosylmethionine. Another V. fischeri gene, ainS, directs the synthesis of N-octanoylhomoserine lactone. The AinS protein shows no significant sequence similarity with LuxI family members, but it does show sequence similarity with the Vibrio harveyi LuxM protein. The luxM gene is required for the synthesis of N-(3-hydroxybutyryl)-L-homoserine lactone. To gain insights about whether AinS and LuxM represent a second family of acylhomoserine lactone synthases, we have purified AinS as a maltose-binding protein (MBP) fusion protein. The purified MBP-AinS fusion protein catalyzed the synthesis of N-octanoylhomoserine lactone from S-adenosylmethionine and either octanoyl-acyl carrier protein or, to a lesser extent, octanoyl coenzyme A. With the exception that octanoyl coenzyme A served as an acyl substrate for the MBP-AinS fusion protein, the substrates for and reaction kinetics of the MBP-AinS fusion protein were similar to those of the several LuxI family members previously studied. We conclude that AinS is an acylhomoserine lactone synthase and that it represents a second family of such enzymes.

Bacterial Proteins↗
PubMed2006

Styryl lactones and their derivatives: biological activities, mechanisms of action and potential leads for drug design.

Nature is an inexhaustible source of natural compounds with interesting biological activities. In general, natural products are an important source of new compounds with a variety of structural arrangements and singular properties. Styryl lactones are a group of secondary metabolites ubiquitous in the genus Goniothalamus that have demonstrated to possess interesting biological properties, in particular antiproliferative activity against cancer cells. In general, the cytotoxicity of styryl lactones appears to be specific against cancer cells since insignificant effects of these compounds on normal cells are reported. A large body of evidence suggests that the antiproliferative activity of styryl lactones is associated with the induction of apoptosis in target cells. In the first part of this review we discuss the biological activities of styryl lactones focusing on cancer cells, the causal agent of Chagas' disease and the vectors for yellow fever and human lymphatic filariasis. Stru described in detail for ninety styryl lactones. The last part describes the molecular targets of styryl lactones for inducing apoptosis, as well as immunosuppressive and inflammatory processes. Overall, understanding how these compounds exert their activities in biological system is essential for future development and application of styryl lactones for human health.

Antineoplastic Agents, Phytogenic↗