Isolation of Scalarane-Type Sesterterpenoids from the Marine Sponge Dysidea sp. and Stereochemical Reassignment of 12-epi-phyllactone D/E

The chemical investigation of the marine sponge Dysidea sp., which was collected from Bohol province in the Philippines, resulted in the identification of 15 new scalarane-type sesterterpenoids (1–14, 16), together with 15 known compounds. The chemical structures of the new compounds were elucidated based on NMR spectroscopy and HRMS. The structure of 12-epi-phyllactone D/E (15) isolated during this study was originally identified in 2007. However, careful inspection of our experimental 13C NMR spectrum revealed considerable discrepancies with the reported data at C-9, C-12, C-14, and C-23, leading to the correction of the reported compound to the C-12 epimer of 15, phyllactone D/E. The biological properties of compounds 1–16 were evaluated using the MDA-MB-231 cancer cell line. Compound 7, which bears a pentenone E-ring, exhibits significant cytotoxicity with a GI50 value of 4.21 μM.

Where Is the Unmatched Transition Metal in Substoichiometric Diboride Line Compounds?

<div>The atomic structure and local composition of high quality epitaxial substoichiometric titanium</div><div>diboride (TiB_1.9) thin film, deposited by unbalanced magnetron sputtering, were studied using</div><div>analytical high-resolution scanning transmission electron microscopy, density functional theory</div><div>and image simulations. The unmatched Ti is pinpointed to planar defects on {1-100} prismatic</div><div>planes and attributed to the absence of B between Ti planes that locally relaxes the structure.</div><div>This mechanism allows the line compound to accommodate the off-stoichiometry and remain</div><div>a line compound between defects. The planar defects are embedded in otherwise stoichiometric</div><div>TiB₂ and are delineated by insertion of dislocations. An accompanied decrease in Ti-Ti bond</div><div>lengths along and across the faults is observed.</div><div>Introduction</div>

Where Is the Unmatched Transition Metal in Substoichiometric Diboride Line Compounds?

<div>The atomic structure and local composition of high quality epitaxial substoichiometric titanium</div><div>diboride (TiB_1.9) thin film, deposited by unbalanced magnetron sputtering, were studied using</div><div>analytical high-resolution scanning transmission electron microscopy, density functional theory</div><div>and image simulations. The unmatched Ti is pinpointed to planar defects on {1-100} prismatic</div><div>planes and attributed to the absence of B between Ti planes that locally relaxes the structure.</div><div>This mechanism allows the line compound to accommodate the off-stoichiometry and remain</div><div>a line compound between defects. The planar defects are embedded in otherwise stoichiometric</div><div>TiB₂ and are delineated by insertion of dislocations. An accompanied decrease in Ti-Ti bond</div><div>lengths along and across the faults is observed.</div><div>Introduction</div>

Anticancer activity of some new series of 2-(substituted)amino-1,3-thiazole derivatives

A series of thiazole derivatives were synthesized and structurally elucidated by IR, 1H NMR, 13C NMR, mass and elemental analyses. The prepared compounds were screened for their cytotoxic activity against Leukemia HL-60 cell line. Compound 4b was considered as the most promising antitumor candidate among the tested compounds. Mechanism of action of compound 4b evaluated by flow cytometric assay revealed cell cycle arrest at G2/M phase and pre-G1 apoptosis. The ratio of apoptosis was also determined. Moreover, compound 4b increased the concentration of caspase 3 by 4 fold more than untreated control.

RISE-HEP project part 1: Treatment sequences evaluation in hepatocellular carcinoma cell lines.

e15663 Background: For over ten years the most stimulating results in systemic therapy for advanced HCC derived from the use of sorafenib (S). But in the last two years several drugs, in particular other multikinase inhibitors like lenvatinib (L), regorafenib (R), cabozantinib (C), proved to be effective both as an alternative or a sequential therapy to sorafenib. In this widened and rapidly increased scenario, without any head-to-head trial, clinicians struggle to define the best drug and the best treatment sequence. Aim of the first part of this project is to evaluate the activity of different treatment sequences in HCC cell lines to pave the way to a future clinical trial investigating their efficacy. Methods: Compounds of S, R, L and C were dissolved in DMSO and aliquoted. HepG2 cell line, obtained from ECACC (Salisbury, UK), was seeded at the density of 3 x 104 cells/ml. After 24 h of incubation, compounds or vehicle (DMSO) were added. Treatments were performed in single administration and six replicates were carried out for each dose. At 48h post-treatment, cells were fixed and stained with acid solution. The absorbance was measured at 520 nm using an ELISA reader (BioTek Instruments, USA). The assay was also performed with the sequences of: S-R, S-C, L-R, L-C (first line treatments for 48h followed by the second compound for 48h). Higher doses than the minimum inhibiting one were tested. Results: S showed superior activity than L as first line compound. In the sequence assay S-C and S-R seems to have the best results in terms of cell viability. After L the best compound appears to be R. See table. Conclusions: Our results showed relevant variations in cell viability with different drug sequences. Already planned analyses in the RISE-HEP project in vivo and in humans are mandatory to confirm which sequence would have the highest efficacy.[Table: see text]

Novel Diamide-Based Benzenesulfonamides as Selective Carbonic Anhydrase IX Inhibitors Endowed with Antitumor Activity: Synthesis, Biological Evaluation and In Silico Insights

In this work, we present the synthesis and biological evaluation of novel series of diamide-based benzenesulfonamides 5a–h as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, II, IX and XII. The target tumor-associated isoforms hCA IX and XII were undeniably the most affected ones (KIs: 8.3–123.3 and 9.8–134.5 nM, respectively). Notably, diamides 5a and 5h stood out as a single-digit nanomolar hCA IX inhibitors (KIs = 8.8 and 8.3 nM). The SAR outcomes highlighted that bioisosteric replacement of the benzylidene moiety, compounds 5a–g, with the hetero 2-furylidene moiety, compound 5h, achieved the best IX/I and IX/II selectivity herein reported with SIs of 985 and 13.8, respectively. Molecular docking simulations of the prepared diamides within CA IX active site revealed the ability of 5h to establish an additional H-bond between the heterocyclic oxygen and HE/Gln67. Moreover, benzenesulfonamides 5a, 5b and 5h were evaluated for their antitumor activity against renal cancer UO-31 cell line. Compound 5h was the most potent derivative with about 1.5-fold more enhanced activity (IC50 = 4.89 ± 0.22 μM) than the reference drug Staurosporine (IC50 = 7.25 ± 0.43 μM). Moreover, 5a and 5h were able to induce apoptosis in UO-31 cells as evidenced by the significant increase in the percent of annexinV-FITC positive apoptotic cells by 22.5- and 26.5-folds, respectively.