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Despite much research and undeniable advances, cancer treatment and prevention has remained a major challenge for scientists. Both genetic and epigenetic changes are involved in the growth and development of cancer complex and multifactorial disease. Among the possible treatment options, multidrug epigenetic therapy such as the use of dual epigenetic inhibitors, has been a popular option in recent years. Histone deacetylases (HDACs) as epigenetic eraser and bromodomain-containing protein 4 (BRD4) as epigenetic reader are epigenetic modifiers, which are rapidly being investigated. Using of a single molecule that simultaneously targets HDACs and BRD4 has been recently employed by medicinal chemists. Presently, there are no approved BRD4 inhibitor and dual BRD4/HDAC inhibitor in the drug market but evidence suggests their possible therapeutic potential in various diseases, such as cancer. In this review, the overall structure of the synthesized dual BRD4/HDAC small molecule inhibitors, lead compounds, and the biological and pharmacological properties of the most potent dual BRD4/HDAC inhibitor in each category are all collected in the hopes of assisting in the development of stronger and more selective dual BRD4/HDAC inhibitors in future studies.

In this study, the Supercritical Carbon Dioxide (scCO

The Doebner reaction is the chemical reaction of an aniline with an aldehyde and pyruvic acid to form quinoline-4-carboxylic acids. Although Doebner reaction is a simple procedure for synthesis of ...

Abstract: Following the outbreak of the coronavirus, global efforts to find a vaccine and drug affecting Covid-19 have been widespread. Reusing some of the available drugs has had relatively satisfactory results. One of the classes of drugs studied against SARS-CoV-2 is the HDAC inhibitors collected in this review. Among the most important points of this study can be mentioned the following: (a) SARS-COV-2 infection can influence the ACE/ACE2-ATR1-Cholesterol-HDAC axis signaling (b) By limiting endocytosis and decreasing ACE2-spike protein recognition at the same time, Romidepsin may hinder SARS-2-S-driven host cell entry. (c) HDAC inhibitors affect the expression of ABO, ACE2 and TMPRSS2 in epithelial cell lines. (d) Valproic acid may help to reduce ARDS as well as hospitalizations and death. (e) Trichostatin A inhibits antigen expression, viral RNA load and infectious particle production in SARS-CoV-2.

HDAC inhibitors and NO donors have both demonstrated independently broad therapeutic potential in a variety of diseases. Borretto et al. presented the topic of NO-HDAC dual inhibitors for the first time in 2013 as an attractive new topic. Here we collected the general structure of all synthesized NO-HDAC dual inhibitors, lead compounds, synthesis methods and biological features of the most potent dual NO-HDAC inhibitor in each category with the intention of assisting in the synthesis and optimization of new drug-like compounds for diverse diseases. Based on studies done so far, NO-HDAC dual inhibitors have displayed satisfactory results against wound healing (3), heart hypertrophy (3), inflammatory, cardiovascular, neuromuscular illnesses (11a-11e) and cancer (6a-6o, 9a-9d, 10a-10d, 16 and 17). NO-HDAC dual inhibitors can have high therapeutic potential for various diseases due to their new properties, NO properties, HDAC inhibitor properties and also due to the effects of NO on HDAC enzymes.

Triblock copolymers of PEG-PCL-PEG (PEGCL) were fabricated using ring opening polymerization (ROP) of ϵ-caprolactone. 1H NMR and FTIR spectra of the PEGCL triblock were used to confirm the structure and determine the molecular weight. The peaks from –OCH3 and –CH2CH2O- in PEG blocks and –(CH2)3–, –COCH2-, and –CH2OCO- within PCL blocks were determined. PEGCL powder was mixed with dexamethasone (DXMT) and then compressed applying a hydraulic pressure of 9 × 10 −2 MPa, which resulted in the formation of disc-like tablets. Following that, the scaffolds with tablet shape were placed into the scCO2 gas foaming apparatus. Central composite design (CCD) was used to obtain the maximum porosity % with the scCO2 variables of soaking time (ts), pressure (P), temperature (T), and time required to depressurize (td). At the maximum porosity % (79.18%), P, T, Ts, and Td were 234 bar, 49 °C, 2.0 h, and 5 min, respectively. Cumulative in-vitro drug release assay revealed that at post-scCO2 treatment, the scaffolds delivered an almost complete release (79.18 ± 1.39%) while at pre-scCO2 treatment, release percentage was 41.07 ± 1.72% after 30 days. This confirmed suitable release time and properties for controlled delivery of the dexamethasone loaded in PEG-PCL-PEG (PEGCL) triblock copolymer-based scaffolds. So, using the scCO2 gas foaming method provides the possibility to construct morphologically and structurally adjustable porous PEG-PCL-PEG scaffolds.

In the title mol-ecule, C(11)H(14)N(4)O(3)S, the tetra-zole and benzene rings are nearly perpendicular to each other, forming a dihedral angle of 104.93 (14)°. The crystal packing exhibits weak inter-molecular C-H⋯O hydrogen bonds.