Correlation between CMC and chromatographic index: simple and effective evaluation of the hydrophobic/hydrophilic balance of bile acids

The discovery that bile acids are involved in the modulation of nuclear steroid receptors has prompted renewed interest in this field of research. Due to the nature of research in this field, a technique that enables simple and effective assessment of the hydrophobic/hydrophilic balance, thus improving and speeding up evaluations of the biological profiles of these compounds, is greatly needed. In this context, both CMC value determination and RP-HPLC mobility evaluation were explored as possible approaches. While the CMC was calculated using the noninvasive conductimetric method, the RP-HPLC mobility was assessed by measuring the retention factor at several mobile phase compositions and extrapolating back to the pure aqueous mobile phase. The correlation of the CMC with the derived chromatographic hydrophobic index ϕ ₀ was satisfactory. Figure Experimental versus predicted pCMC values     

1,2,3-Triazolo[4,5-e]-1,2,4-triazolo[3,4-c]pyrimidines

Some new 1,2,3-triazolo[4,5-e]-1,2,4-triazolo[3, 4 -c]pyrimidmes were prepared starting from the corresponding 1,2,3-triazolo[4,5-d]pyrimidines via the formation of the 1,2,4-triazole ring. Thus suitable hydrazino derivatives 6 were condensed with triethyl orthoformate, triethyl orthoacetate and triethyl orthobenzoate to give the expected tricyclic derivatives 7 , 8 and 9 . Intramolecular cyclization of the ethoxycarbonylhydrazino derivatives 10 gave the tricyclic compounds 11 bearing an hydroxyl group in the 3 position. The v-triazolo-s-triazolopyrimidine derivatives were tested towards the A₁ and A_2A adenosine receptors in binding assays, but they did not show any receptor affinity.     

Dipeptides containing D-serine or D-isoserine from the same (R)-aziridine-2-imide by a simple reversal of the synthetic procedure

The ring expansion of 3-unsubstituted (R)-aziridine-2-imide-containing dipeptide under acidic conditions gives rise to oxazoline-5-imide regio and stereoselectively, which can be hydrolysed to the dipeptide containing D-isoserine. On the other hand, the ring opening of 3-unsubstituted (R)-aziridine-2-ester dipeptide, easily obtained from the same (R)-aziridine, gives the regioisomeric dipeptide containing D-serine.     

An Experimental Evidence of a Metal−Metal Bond in μ‐Carbonylhexacarbonyl[μ‐(5‐oxofuran‐2(5H)‐ylidene‐κC,κC)]‐dicobalt(Co−Co)[Co2(CO)6(μ‐CO)(μ‐C4O2H2)]

The orthorhombic crystal structure of [Co₂(CO)₆(μ‐CO)(μ‐C₄O₂H₂)] ( 1 ) was determined at 150 K (Fig. 1). Two C−H⋅⋅⋅O bonds connect the molecules, forming waving ribbons along the b axis. The experimental electron density, determined with the aspherical‐atom formalism, was analyzed with the topological theory of molecular structure. The presence of the Co−Co bond critical point indicates for the first time the existence of a metal−metal bond in a system with bridged ligands. The bond critical properties of the intramolecular bonds and of the intermolecular interactions show features similar to those found in [Mn₂(CO)₁₀], confirming our previously established bonding classification for organometallic and coordination compounds.     

Labdane Diterpenoids from Salvia tingitana Etl. Synergize with Clindamycin against Methicillin-Resistant Staphylococcus aureus

Quorum-sensing (QS) is a regulatory mechanism in bacterial communication, important for pathogenesis control. The search for small molecules active as quorum-sensing inhibitors (QSI) that can synergize with antibiotics is considered a good strategy to counteract the problem of antibiotic resistance. Here the antimicrobial labdane diterpenoids sclareol (1) and manool (2) extracted from Salvia tingitana were considered as potential QSI against methicillin-resistant Staphylococcus aureus. Only sclareol showed synergistic activity with clindamycin. The quantification of these compounds by LC–MS analysis in the organs and in the calli of S. tingitana showed that sclareol is most abundant in the flower spikes and is produced by calli, while manool is the major labdane of the roots, and is abundant also in the leaves. Other metabolites of the roots were abietane diterpenoids, common in Salvia species, and pentacyclic triterpenoids, bearing a γ-lactone moiety, previously undescribed in Salvia. Docking simulations suggested that 1 and 2 bind to key residues, involved in direct interactions with DNA. They may prevent accessory gene regulator A (AgrA) binding to DNA or AgrA activation upon phosphorylation, to suppress virulence factor expression. The antimicrobial activity of these two compounds probably achieves preventing upregulation of the accessory gene regulator (agr)-regulated genes.     

A New Kid on the Block: Sacituzumab Govitecan for the Treatment of Breast Cancer and Other Solid Tumors

Human trophoblast cell-surface antigen-2 (Trop-2) is a membrane glycoprotein involved in cell proliferation and motility, frequently overexpressed in epithelial tumors. Thus, it represents an attractive target for anticancer therapies. Sacituzumab govitecan (SG) is a third-generation antibody-drug conjugate, consisting of an anti-Trop-2 monoclonal antibody (hRS7), a hydrolyzable linker, and a cytotoxin (SN38), which inhibits topoisomerase 1. Specific pharmacological features, such as the high antibody to payload ratio, the ultra-toxic nature of SN38, and the capacity to kill surrounding tumor cells (the bystander effect), make SG a very promising drug for cancer treatment. Indeed, unprecedented results have been observed with SG in patients with heavily pretreated advanced triple-negative breast cancer and urothelial carcinomas, and the drug has already received approval for these indications. These results are coupled with a manageable toxicity profile, with neutropenia and diarrhea as the most frequent adverse events, mainly of grades 1–2. While several trials are exploring SG activity in different tumor types and settings, potential biomarkers of response are under investigation. Among these, Trop-2 overexpression and the presence of BRCA1/2 mutations seem to be the most promising. We review the available literature concerning SG, with a focus on its toxicity spectrum and possible biomarkers of its response.     

Fantappié-Arcidiacono Spacetime and Its Consequences in Quantum Cosmology

Einstein’s gravitational theory gave rise to a new conception of the Universe and Cosmology has been enclosed in the realm of Science and not only of Philosophy as before the Einstein work. Despite this, the presence of the Big Bang singularity, flatness and horizon problems led to the statement that Standard Cosmological Model, based on General Relativity and Standard Model of particle physics, is inadequate to describe the Universe in extreme regimes. Due to this facts, alternative gravitational theories and alternative approaches to cosmology have been proposed during the years. One of the most fruitful approach has been that of Projective Relativity and, in this paper, we analyze the developments of this theory. Projective Relativity, initially proposed by Fantappié and subsequently developed by Arcidiacono, has been recently revisited by prof. Ignazio Licata and other authors. The cosmological consequences of such extension appear relevant. In the following, we analyze the effects of the group approach on the metrics and on the dynamics and we will consider its properties in connection with varying speed of light.     

Reactions of Co2(CO)8 and of Co2(CO)6L (L = 3-pentyn-1-ol, 1,4-butyn-diol or 2-methyl-3-butyn-2-ol) with 2(diphenylphosphino)ethyl-trietoxysilane and tris(hydroxymethyl)phosphine for applications to new sol-gel materials

The complex Co₂(CO)₆[μ-η²-(H₃CCCCH₂CH₂OH)] (1) with the ligand 3-pentyn-1-ol (pol) has been synthesized following established procedures. Its structure has been determined by X-ray analysis. The complex Co₂(CO)₆(mbo) (mbo = 2-methyl-3-butyn-2-ol, HCCC(CH₃)₂OH), (3), along with the already known Co₂(CO)₆(bud) (bud = 1,4-butyn-diol, HOCH₂CCCH₂OH) (2), and Co₂(CO)₈ were reacted with 2(diphenylphosphino)ethyl-triethoxysilane [Ph₂PCH₂CH₂Si(OCH₂CH₃)₃] (dpts) and tris(hydroxymethyl)phosphine [P(CH₂OH)₃] (thp). With dpts, mono- and di-substituted complexes were obtained: these were characterized by analytical and spectroscopic techniques. The structures of Co₂(CO)₆(dpts)₂ (5) and of Co₂(CO)₄(pol)(dpts)₂ (8) have been determined by X-ray analysis.Complex (1) was reacted with 3-(triethoxysilyl)propyl isocyanate [(H₃CCH₂O)₃Si(CH₂)₃NCO] (tsi): the new complex Co₂(CO)₆[H₃CCCCH₂CH₂OC(O)NH(CH₂)₃Si(OCH₂CH₃)₃] (9) was obtained and spectroscopically characterized. The complex has also been reacted with tetraethyl orthosilicate (teos); a new inorganic-organometallic material was obtained. Complex (5) has been grafted on the mesoporous material SBA-15. The hybrid inorganic-organometallic materials obtained have been characterized by inductively coupled plasma-mass spectrometry (ICP-MS), infrared spectroscopy (FT-IR) under vacuum conditions, X-ray diffraction (XRD) and scanning electron microscopy coupled to EDS probe (SEM-EDS).     

ESI-MS and MALLS analysis of quaternary structure of molluscan hemocyanins

The understanding of the function of macromolecular complexes is mainly related to a precise knowledge of their structure. Recently, the development of suitable mass spectrometric techniques (electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI)) and multi-angle laser light scattering has enabled mass determination of native complexes and of their subunits. By these techniques, the structure and association/dissociation behavior of huge molecules of molluscan Octopus vulgaris, Sepia officinalis and Rapana venosa have been characterized. Molecular masses of the native and dissociated molecule of cephalopodan Hcs O. vulgaris (3545 and 359.3?kDa, respectively) and S. officinalis (4134 and 443.8?kDa, respectively) revealed that only one type subunit organizes their molecules, while the presence of two isoforms with different masses (422.8 and 400.0?kDa) has been determined for gastropodan R. venosa Hc, aggregated into didecamers. The difference of their structural subunits was also established after limited proteolysis with TPCK-trypsin. Eight functional units (FUs) with masses of?~?50?kDa were isolated from both subunits of RvH and isoform of Sepia officinalis, while seven FUs were purified from OvH. Further characterization of proteins by ESI-mass spectrometry (MS) and MALDI-MS, methods gave insights into post-translational modifications such as glycosylation. Glycosylation of O. vulgaris and S. officinalis Hcs was suggested based on the differences (11.6 and 40.0?kDa, respectively) between the masses measured by ESI-MS and those calculated by their gene sequences.