C5 Epimer Research Articles

Exploration of vitamin D hydroxy metabolites C3 epimers in cardiovascular patients: comparative cross-sectional study

Abstract Background Research on vitamin D deficiency has recently surged in popularity. This issue has been acknowledged as a widespread problem, often called a "pandemic", and approximately 90% of the Polish population suffers from vitamin D deficiency. The 3-epi-25(OH)D2 and 3-epi-25(OH)D3 metabolites are stereoisomers of 25(OH)D2 and 25(OH)D3 metabolites, and they may be accidentally measured when determining 25(OH)D levels and result in overestimating metabolite concentrations. Purpose Our study aims to identify vitamin D hydroxy metabolites (25-hydroxyvitamin D2, 25-hydroxyvitamin D3, and their epimers 3-epi-25-hydroxyvitamin D2 and 3-epi-25-hydroxyvitamin D3) in patients with cardiovascular disease and healthy volunteers. To our knowledge, no similar studies have been conducted on this topic. Method We included 27 adult patients with venous thrombosis (fourteen males and thirteen females, aged 64.11±14.84 years) and 35 healthy volunteers (thirty-three females and two males, aged 36.37±12.29 years). We used our validated UPLC-MS/MS method to measure the concentrations of 25(OH)D2, 25(OH)D3, 3-epi-25(OH)D2, and 3-epi-25(OH)D3. Statistica 13.3 with Plus Kit 3.0 was used for the statistical assessment. Normal variables were represented as mean and standard deviation, and non-normal variables as the median and interquartile range. A P-value < 0.05 was considered statistically significant for all tests. Results Patients had significantly lower levels of epi-25(OH)D2 than the healthy control group (0.6 [0.4] ng/mL vs. 2.2 [1.3-4.3] ng/mL, p = 0.004). Similarly, they exhibited significantly lower levels of %epi-25(OH)D2 (8.6 [6-22.3] % vs. 39.4 [18.5] %, p = 0.035). Females had higher levels of 25(OH)D3 than males (26.5 [16.2-37.9] ng/mL vs. 18.8 [7.5] ng/mL, p = 0.04). They also exhibited higher levels of total 25(OH)D3 (30.3 [15.6] ng/mL vs. 19.4 [7.8] ng/mL, p = 0.016). Higher age (OR 1.12, 95% CI 1.07 to 1.18), being male (OR 17.77, 95% CI 3.54 to 89.3), and lower % 3-epi-25(OH)D2 (OR 0.92, 95% CI 0.84 to 0.998) were univariate predictors for patients with venous thrombosis. Conclusion: Demographic factors within a given population may affect the 25(OH)D3 concentration. The results indicate that vitamin D epimeric metabolites, particularly epi-25(OH)D2, and their percentage were different in patients compared to healthy volunteers. Additional studies involving a larger population are necessary to fully comprehend the relationship between these vitamin D epimeric metabolites and cardiovascular health

Novel 99mTc-Labeled Mannose Derivative as a Highly Promising Single Photon Emission Computed Tomography Probe for Tumor Imaging.

18F-2-fluoro-2-deoxy-d-glucose ([18F]FDG) has been the most used positron emission tomography imaging agent for clinical applications. Single photon emission computed tomography (SPECT) imaging is cheaper and used more widely for diagnostic use, but there is no SPECT tumor imaging agent for clinical applications comparable to [18F]FDG. Mannose is a C2 epimer of glucose and can also be transported into tumor cells via glucose transporters (GLUTs). To develop a novel SPECT tumor imaging agent with satisfactory tumor uptake and tumor/nontarget ratios, here a mannose derivative (CN7DM) was synthesized and radiolabeled with technetium-99m to prepare [99mTc]Tc-CN7DM. The six-coordinated structure of [99mTc]Tc-CN7DM was confirmed by the corresponding rhenium compound (Re-CN7DM). [99mTc]Tc-CN7DM was transported into cancer cells via GLUTs and may be trapped in the cancer cells by electrostatic attraction. The probe exhibited high uptake in tumors and low uptake in nontarget tissues in mice bearing different tumors, indicating that [99mTc]Tc-CN7DM exhibited promising potential for SPECT tumor imaging and warranted further clinical investigation.

Development and validation of LC-MS/MS for quantifying omadacycline from stool for gut microbiome studies

This study developed and validated a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify omadacycline and its epimerization in stool to facilitate microbiome studies. Omadacycline was extracted in a methanol-water-ethylenediaminetetraacetic acid (ETDA) solvent containing deuterated omadacycline as internal standard, followed by dilution. In an optimal gradient elution mode, omadacycline and its C4 epimer were separated within 5 min on reversed-phase C18 column. The method showed a broad working range of 0.1–200 ng/ml with a limitation of detection (LOD) of 0.03 ng/ml, little fecal matrix effect, good intra-day and inter-day accuracy (90–101 %), precision (2–15 %), and recovery rate (99–105 %). The method was sufficiently sensitive to quantify omadacycline in human fecal samples (n = 82) collected during a 10-day therapy course and at follow-up (day 13 and day 30) that ranged from 1 to 4785 µg/g. Further analysis revealed that ∼9 % of omadacycline was epimerized in fecal matrix control while, on average, 37.4 % was epimerized in human fecal samples. This study developed and validated a novel, simple, sensitive, and accurate method utilizing LC-MS/MS to quantify omadacycline its epimerization in the human gut. This has important implications for future studies of omadacycline and other tetracycline-class antibiotics as part of gut microbiome studies.

Total Synthesis of Tetracyclic Spirooxindole Alkaloids via a Double Oxidative Rearrangement/Cyclization Cascade.

Skeleton rearrangement could rapidly transfer simple molecules to complex structures and has significant potential in the total synthesis of natural products. We developed a one-pot reaction cascade of double oxidative rearrangement of furan and indole followed by a nucleophilic cyclization that was successfully applied for the formal synthesis of rhynchophylline/isorhynchophylline and the first total synthesis of (±)-7(R)-geissoschizol oxindole/(±)-7(S)-geissoschizol oxindole. In addition, the geissoschizol oxindoles were revised to their C3 epimers, and the mechanism for the reversed stereochemistry through the retro-Mannich/Mannich cascade was proposed and supported by density functional theory calculations.

Systematic Investigation of Cellular Response to Hydroxyl Group Orientation Differences on Gold Glyconanoparticles.

Nanoparticle (NP) surfaces act as the interface as they interact with living systems and play a critical role in defining their cellular response. The nature of these interactions should be well understood to design safer and more effective NPs to be used in a wide range of biomedical applications. At the moment, it is not clear how a subtle change in surface chemistry will affect an NP's behavior in a biological system. Thus, understanding the role of such a small change is critical and may allow one to fine-tune a biological response. In this study, the cellular response to -OH orientation differences generated on gold glyconanoparticles, which are recently considered promising therapeutic agents as they mimic a glycocalyx, is investigated. As model molecules, glucose and mannose (C2 epimer) as monosaccharides and lactose and maltose (galactose and glucose as free units, C4 epimer) as disaccharides were chosen to monitor the cellular response in A549, BEAS-2b, and MDA-MB-231 cells through cellular uptake, cytotoxicity, and cell cycle progression. The three cell lines gave various and remarkable cellular responses to the same subtle -OH differences on gold glyconanoparticles, and it is determined that not only -OH orientation differences but also the number of saccharides on gold glyconanoparticles affect the cellular response. It was shown that mannose (C2 epimer to glucose) was significant with the promise of being a therapeutic agent for lung cancer therapy, whereas the toxicological profile of MDA-MB-231 cells was affected by AuNPs-glucose the most. This study demonstrates that clearly small chemical alterations on a NP surface can result in a significant cellular response. It can be concluded that the -OH orientation at the second and fourth carbon of a carbohydrate ring has a critical role in designing and engineering novel gold glyconanoparticles (consisting of monolayer mono- or disaccharides) for a specific cancer therapy.

Enzymatic depolymerization of alginate by two novel thermostable alginate lyases from Rhodothermus marinus.

Alginate (alginic acid) is a linear polysaccharide, wherein (1→4)-linked β-D-mannuronic acid and its C5 epimer, α-L-guluronic acid, are arranged in varying sequences. Alginate lyases catalyze the depolymerization of alginate, thereby cleaving the (1→4) glycosidic linkages between the monomers by a β-elimination mechanism, to yield unsaturated 4-deoxy-L-erythro-hex-4-enopyranosyluronic acid (Δ) at the non-reducing end of resulting oligosaccharides (α-L-erythro configuration) or, depending on the enzyme, the unsaturated monosaccharide itself. In solution, the released free unsaturated monomer product is further hydrated in a spontaneous (keto-enol tautomerization) process to form two cyclic stereoisomers. In this study, two alginate lyase genes, designated alyRm3 and alyRm4, from the marine thermophilic bacterium Rhodothermus marinus (strain MAT378), were cloned and expressed in Escherichia coli. The recombinant enzymes were characterized, and their substrate specificity and product structures determined. AlyRm3 (PL39) and AlyRm4 (PL17) are among the most thermophilic and thermostable alginate lyases described to date with temperature optimum of activity at ∼75 and 81°C, respectively. The pH optimum of activity of AlyRm3 is ∼5.5 and AlyRm4 at pH 6.5. Detailed NMR analysis of the incubation products demonstrated that AlyRm3 is an endolytic lyase, while AlyRm4 is an exolytic lyase, cleaving monomers from the non-reducing end of oligo/poly-alginates.

Valeridoids G - Q, Eleven seco-Iridoids from Valeriana jatamansi and Their Bioactivites.

Eleven new seco-iridoids, valeridoids G-Q (1-6 and 8-12), along with four known products, 9-epi-valtral C (7), desacylbaldrinal (13), 11-methoxyviburtinal (14) and baldrinal (15), were obtained from Valeriana jatamansi. Among them, the new compounds were identified by their NMR, HR-ESI-MS spectroscopic data and ECD calculation. Moreover, valeridoid N and O were a pair of C3 epimers, whose ether bonds between C-1 and C-3 opened, and new ether bonds formed between C-3 and C-6. Valeridoid Q belonged to the C-1 degradation of seco-iridoids. As a result, 9-epi-valtral C displayed significant inhibition on Streptococcus agalactiae, Staphylococcus aureus, Staphylococcus argenteus, Shigella flexneri and Klebsiella pneumoniae, and valeridoid Q exhibited the most significant inhibition against Salmonella enteritidis. 9-Epi-valtral C and baldrinal selectively inhibited the growth of human glioma stem cells. Valeridoid Q exhibited significant anti-influenza activity, while valeridoid O inhibited nitric oxide production.

An LC-MS/MS Method for Analysis of Vitamin D Metabolites and C3 Epimers in Mice Serum: Oral Supplementation Compared to UV Irradiation.

Introduction: The most common forms of vitamin D in human and mouse serum are vitamin D3 and vitamin D2 and their metabolites. The aim of this study is to determine whether diet and sunlight directly affect the circulating concentrations of vitamin D metabolites in a mouse model. We investigated the serum concentrations of eight vitamin D metabolites—vitamin D (vitamin D3 + vitamin D2), 25OHD (25OHD3 + 25OHD2), 1α25(OH)2D (1α25(OH)2D2, and 1α25(OH)2D3)—including their epimer, 3-epi-25OHD (3-epi-25OHD3 and 3-epi-25OHD2), and a bile acid precursor 7alpha-hydroxy-4-cholesten-3-one (7αC4), which is known to cause interference in liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Method: The LC-MS/MS method was validated according to FDA-US guidelines. The validated method was used for the analysis of mouse serum samples. Forty blood samples from mice were collected and divided into three groups. The first group, the DDD mice, were fed a vitamin D-deficient diet (25 IU VD3/kg of diet) and kept in the dark; the second group, the SDD mice, were maintained on a standard-vitamin D diet (1000 IU VD3) and kept in the dark; and the third group, SDL, were fed a standard-vitamin D diet (1000 IU VD3) but kept on a normal light/dark cycle. LC-MS/MS was used for the efficient separation and quantitation of all the analytes. Results: The validated method showed good linearity and specificity. The intraday and interday precision were both <16%, and the accuracy across the assay range was within 100 ± 15%. The recoveries ranged between 75 and 95%. The stability results showed that vitamin D metabolites are not very stable when exposed to continuous freeze–thaw cycles; the variations in concentrations of vitamin D metabolites ranged between 15 and 60%. The overlapping peaks of vitamin D, its epimers, and its isobar (7αC4) were resolved using chromatographic separation. There were significant differences in the concentrations of all metabolites of vitamin D between the DDD and SDL mice. Between the groups SDD (control) and SDL, a significant difference in the concentrations of 3-epi-25OHD was noted, where C3 epimer was about 30% higher in SDL group while no significant differences were noted in the concentrations of vitamin D, 25OHD, 1α25(OH)2D, and 7αC4 between SDD and SDL group. Conclusions: A validated method, combined with a simple extraction technique, for the sensitive LC-MS/MS determination of vitamin D metabolites is described here. The method can eliminate the interferences in LC-MS/MS analysis caused by the overlapping epimer and isobar due to them having the same molecular weights as 25OHD. The validated method was applied to mouse serum samples. It was concluded that a standard-vitamin D diet causes an increase in the proportion of all the vitamin D metabolites and C3 epimers and isobar, while UV light has no pronounced effect on the concentrations of the majority of the vitamin D metabolites except 3-epi-25OHD. Further studies are required to confirm this observation in humans and to investigate the biochemical pathways related to vitamin D’s metabolites and their epimers.

Sulfamate-tethered aza-Wacker approach towards analogs of Bactobolin A.

Here, we describe an approach towards analogs of the potent antibiotic Bactobolin A. Sulfamate-tethered aza-Wacker cyclization reactions furnish key synthons, which we envision can be elaborated into analogs of Bactobolin A. Docking studies show that the C4 epimer of Bactobolin A and the C4/C6 diastereomer interact with different residues of the 23S rRNA (bacterial ribosome 50S subunit) than the natural product, suggesting that these molecules could be valuable tool compounds for fundamental studies of the bacterial translational machinery.

Cryogenic Infrared Spectroscopy Reveals Structural Modularity in the Vibrational Fingerprints of Heparan Sulfate Diastereomers.

Heparan sulfate and heparin are highly acidic polysaccharides with a linear sequence, consisting of alternating glucosamine and hexuronic acid building blocks. The identity of hexuronic acid units shows a variability along their sequence, as d-glucuronic acid and its C5 epimer, l-iduronic acid, can both occur. The resulting backbone diversity represents a major challenge for an unambiguous structural assignment by mass spectrometry-based techniques. Here, we employ cryogenic infrared spectroscopy on mass-selected ions to overcome this challenge and distinguish isomeric heparan sulfate tetrasaccharides that differ only in the configuration of their hexuronic acid building blocks. High-resolution infrared spectra of a systematic set of synthetic heparan sulfate stereoisomers were recorded in the fingerprint region from 1000 to 1800 cm-1. The experiments reveal a characteristic combination of spectral features for each of the four diastereomers studied and imply structural modularity in the vibrational fingerprints. Strong spectrum-structure correlations were found and rationalized by state-of-the-art quantum chemical calculations. The findings demonstrate the potential of cryogenic infrared spectroscopy to extend the mass spectrometry-based toolkit for the sequencing of heparan sulfate and structurally related biomolecules.

D-galactose catabolism in archaea: operation of the DeLey-Doudoroff pathway in Haloferax volcanii.

The haloarchaeon Haloferax volcanii was found to grow on D-galactose as carbon and energy source. Here we report a comprehensive analysis of D-galactose catabolism in H. volcanii. Genome analyses indicated a cluster of genes encoding putative enzymes of the DeLey-Doudoroff pathway for D-galactose degradation including galactose dehydrogenase, galactonate dehydratase, 2-keto-3-deoxygalactonate kinase and 2-keto-3-deoxy-6-phosphogalactonate (KDPGal) aldolase. The recombinant galactose dehydrogenase and galactonate dehydratase showed high specificity for D-galactose and galactonate, respectively, whereas KDPGal aldolase was promiscuous in utilizing KDPGal and also the C4 epimer 2-keto-3-deoxy-6-phosphogluconate as substrates. Growth studies with knock-out mutants indicated the functional involvement of galactose dehydrogenase, galactonate dehydratase and KDPGal aldolase in D-galactose degradation. Further, the transcriptional regulator GacR was identified, which was characterized as an activator of genes of the DeLey-Doudoroff pathway. Finally, genes were identified encoding components of an ABC transporter and a knock-out mutant of the substrate binding protein indicated the functional involvement of this transporter in D-galactose uptake. This is the first report of D-galactose degradation via the DeLey-Doudoroff pathway in the domain of archaea.

Advances in Application of Alginate Lyase And Its Enzymatic Hydrolysate

Alginate is a linear, water-soluble acidic seaweed polysaccharide composed of L-guluronic acid and its C5 epimer D-mannuronic acid, a general term for hydrophilic derivatives of alginic acid. It is widely found in various brown algae. Alginate lyase and its enzymatic hydrolysate have a variety of biological activities and become a new research hotspot. This paper reviews the source, classification, enzymatic mechanism and enzymatic properties of alginate lyase, and summarizes the function and application of alginate lyase and its enzymatic hydrolysate brown algal oligosaccharide, in order to provide a base for the development and application of alginate lyase and its products.

Efficiently Anti-Obesity Effects of Unsaturated Alginate Oligosaccharides (UAOS) in High-Fat Diet (HFD)-Fed Mice.

Obesity and its related complications have become one of the leading problems affecting human health. However, current anti-obesity treatments are limited by high cost and numerous adverse effects. In this study, we investigated the use of a non-toxic green food additive, known as unsaturated alginate oligosaccharides (UAOS) from the enzymatic degradation of Laminaria japonicais, which showed effective anti-obesity effects in a high-fat diet (HFD) mouse model. Compared with acid hydrolyzed saturated alginate oligosaccharides (SAOS), UAOS significantly reduced body weight, serum lipid, including triacylglycerol (TG), total cholesterol (TC) and free fatty acids (FFA), liver weight, liver TG and TC, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels, adipose mass, reactive oxygen species (ROS) formation, and accumulation induced in HFD mice. Moreover, the structural differences in β-d-mannuronate (M) and its C5 epimer α-l-guluronate (G) did not cause significant functional differences. Meanwhile, UAOS significantly increased both AMP-activated protein kinase α (AMPKα) and acetyl-CoA carboxylase (ACC) phosphorylation in adipocytes, which indicated that UAOS had an anti-obesity effect mainly through AMPK signaling. Our results indicate that UAOS has the potential for further development as an adjuvant treatment for many metabolic diseases such as fatty liver, hypertriglyceridemia, and possibly diabetes.

The Characterization of 18F-hGTS13 for Molecular Imaging of xC- Transporter Activity with PET.

The aim of this study was development of an improved PET radiotracer for measuring xC- activity with increased tumor uptake and reduced uptake in inflammatory cells compared with (S)-4-(3-18F-fluoropropyl)-l-glutamate (18F-FSPG). Methods: A racemic glutamate derivative, 18F-hGTS13, was evaluated in cell culture and animal tumor models. 18F-hGTS13 was separated into C5 epimers, and the corresponding 18F-hGTS13-isomer1 and 18F-hGTS13-isomer2 were evaluated in H460 tumor-bearing rats. Preliminary studies investigated the cellular uptake of 18F-hGTS13-isomer2 in multiple immune cell populations and states. Results:18F-hGTS13 demonstrated excellent H460 tumor visualization with high tumor-to-background ratios, confirmed by ex vivo biodistribution studies. Tumor-associated radioactivity was significantly higher for 18F-hGTS13 (7.5 ± 0.9 percentage injected dose [%ID]/g, n = 3) than for 18F-FSPG (4.6 ± 0.7 %ID/g, n = 3, P = 0.01). 18F-hGTS13-isomer2 exhibited excellent H460 tumor visualization (6.3 ± 1.1 %ID/g, n = 3) and significantly reduced uptake in multiple immune cell populations relative to 18F-FSPG. 18F-hGTS13-isomer2 exhibited increased liver uptake relative to 18F-FSPG (4.6 ± 0.8 vs. 0.7 ± 0.01 %ID/g), limiting its application in hepatocellular carcinoma. Conclusion:18F-hGTS13-isomer2 is a new PET radiotracer for molecular imaging of xC- activity that may provide information on tumor oxidation states. 18F-hGTS13-isomer2 has potential for clinical translation for imaging cancers of the thorax because of the low background signal in healthy tissue.

Chemoenzymatic Synthesis of Hygromycin Aminocyclitol Moiety and its C2 Epimer

This manuscript describes the enantioselective synthesis of the aminocyclitol moiety of the antibiotic hygromycin A in eight steps and 39 % overall yield from a non‐chiral starting material. The sequence made use of an initial enzymatic step to transfer chirality to an aromatic ring and was followed by selective organic chemistry transformations (oxidation, protection, azidation, hydrolysis) of the six‐membered ring in order to achieve the target. The approach is also amenable to the synthesis of other related unnatural analogues as exemplified by the synthesis of the C2 epimer of the natural aminocyclitol. All the intermediates were fully characterized, and the absolute stereochemistry assigned by spectrometric methods.

Total Synthesis of Natural Hyacinthacine C5 and Six Related Hyacinthacine C5 Epimers.

The total synthesis of natural (+)-hyacinthacine C5 was achieved, which allowed correction of its initially proposed structure, as well as six additional hyacinthacine C-type compounds. These compounds were readily accessible from two epimeric anti-1,2-amino alcohols. Keeping a common A-ring configuration, chemical manipulation occurred selectively on the B-ring of the hyacinthacine C-type products through methods of syn-dihydroxylation, SN2 ring-opening of a cyclic sulfate, and also employing either ( R)- or ( R, S)-α-methylallyl amine for the Petasis borono Mannich reaction. Our small analogue library was then assessed for its glycosidase inhibitory potency against a panel of glycosidases. (-)-6- Epi-hyacinthacine C5 and (+)-7- epi-hyacinthacine C5 (compound names are based on the corrected structure of hyacinthacine C5) proved most active, with inhibitory activities ranging between weak (IC50 = 130 μM) and moderate (IC50 = 9.9 μM) against the α-glucosidases of rat intestinal maltase, isomaltase, and sucrase, thus identifying potential new leads for future antidiabetic drug development.

Mechanistic Implications of the Deamination of TDP-4-amino-4-deoxy-d-fucose Catalyzed by the Radical SAM Enzyme DesII.

DesII is a radical SAM lyase that catalyzes a deamination reaction during the biosynthesis of desosamine in Streptomyces venezuelae. Competing mechanistic hypotheses for this radical-mediated reaction are differentiated according to whether a 1,2-migration takes place and the timing of proton abstraction following generation of a substrate α-hydroxyalkyl radical intermediate. In this study, the deuterated C4 epimer of the natural substrate, TDP-4-amino-4-deoxy-d-[3-2H]fucose, was prepared and shown to be a substrate for DesII undergoing deamination alone with a specific activity that is only marginally reduced (∼3-fold) with respect to that of deamination of the natural substrate. Furthermore, pH titration of the deamination reaction implicates the presence of a hydron acceptor that facilitates catalysis but does not appear to be necessary. On the basis of these as well as previously reported results, a mechanism involving direct elimination of ammonium with concerted proton transfer to the nucleofuge from the adjacent α-hydroxyalkyl radical is proposed.

An efficient synthesis of the 1,6-dioxaspiro[4.4]nonan-2-one motif of the immunosuppressive triterpenoid Phainanoid F

We describe an efficient synthesis of the 1,6-dioxaspiro[4.4]nonan-2-one motif of the immunosuppressive triterpenoid Phainanoid F and its C4 epimer. A furan oxidative spirocyclization for constructing the spiro center was used as the key step. Other important reactions involved Sharpless asymmetric dihydroxylation, Weinreb ketone synthesis and Yamaguchi esterfication. The synthesis was achieved in 11 linear steps with 17.3% overall yield.

Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives

AbstractThe semisynthesis and biological activity of the naturally occurring abietane diterpenoids callitrisic acid (4a; 4-epidehydroabietic acid) and callitrisinol (6) are reported. These compounds and jiadifenoic acid C (5) were obtained from methyl callitrisate (4b) isolated from Sandarac resin for biological evaluation and comparison with the biological activities of C4 epimers such as dehydroabietic acid (2a). In particular, the antiproliferative activity against a panel of six representative human solid tumor cell lines (A549, HBL-100, HeLa, SW1573, T-47D, WiDr) and the effect on GABAA receptors (α 1 β 2 γ 2s) were evaluated. The GI50 values were in the range of 3.4–61 µM and the potentiation of IGABA was 269–311% at 100 µM. Callitrisinol (6) was found to be 6.7-fold more potent than the reference etoposide in the WiDr (colon) cancer cell line. The role of the stereogenic center at C4 for antiproliferative and GABAA receptor modulating activities in the dehydroabietane scaffold has thus been revealed.

Self-association of C3 and C6 epimers of hyodeoxycholate anions in aqueous medium: Hydrophobicity, critical micelle concentration and aggregation number

Hyodeoxycholic acids anion (HD) and it's 3- and 6-epimers (3e-HD and 6e-HD) are suitable for biopharmaceutical application since they possess α equatorial i.e. β axial OH groups so their membranotoxicity is reduced. Self-association of stereoisomers 3e-HD and 6e-HD has not been studied so far. According to the capacity factor (k, RPHPLC), hydrophobicity decreases in the following series: HD>3e-HD>6e-HD. However, critical micelle concentration (CMC) is the lowest for the 6e-HD (10mM, 25°C) and the highest for 3e-HD (38mM, 25°C), which is contrary to expectations according to their hydrophobicity. Aggregation number (n) has the highest value for 6e-HD (8, 25°C) and the lowest value for the stereoisomer 3e-HD (4, 25°C). The change in demicellisation capacity factor (∆Cp) decreases in the following series: 6e-HD (316Jmol−1K−1)>HD (260Jmol−1K−1)>3e-HD (181Jmol−1K−1). In the plane of ln k – ln CMC epimer 6e-HD is outliner related to the hydrophobic congeneric group. This suggests that, in formation of micelles of HD and 3e-HD, besides hydrophobic effect other interactions are neglected. However, in formation of 6e-HD micelle, beside hydrophobic effect significant interaction exists different from hydrophobic interaction (formation of hydrogen bonds between building units of the micelle).