Tailored Tetrasubstituted Imidazole Carrying the Benzenesulfonamide Fragments as Selective Human Carbonic Anhydrase IX/XII Inhibitors.

A new series of tetrasubstituted imidazole carrying sulfonamide as zinc-anchoring group has been designed. The structures of the synthesized derivatives 5 a-l have been confirmed by spectroscopic analysis. These compounds incorporate an ethylenic spacer between the benzenesulfonamide and the rest of the trisubstituted imidazole moiety and were tested as inhibitors of carbonic anhydrases and for in-vitro cytotoxicity.

Anti-inflammatory effect of 3-fluorophenyl pyrimidinylimidazo[2,1-b]thiazole derivatives as p38α inhibitors.

In the present work, the anti-inflammatory effect of 30 compounds containing 3-fluorophenyl pyrimidinylimidazo[2,1-b]thiazole was investigated. All final target compounds showed significant Inhibitory effect on p38α. P38α is considered one of the key kinases in the inflammatory process due to its regulatory effect on pro-inflammatory mediators.

Anticancer Activities of Tetrasubstituted Imidazole-Pyrimidine-Sulfonamide Hybrids as Inhibitors of EGFR Mutants.

A new series of tetrasubstituted imidazole derivatives carrying pyrimidine sulfonamide pharmacophores has been synthesized and evaluated for their anticancer activities. In-vitro screening of these hybrids against a full 60-cell-line panel at a single dose of 10 μM showed significant growth inhibition of up to 95 %. The most active compound showed in-vitro anticancer activities against (i) abnormal HER2 and (ii) two mutants for EGFR.

Design and synthesis of novel rigid dibenzo[]azepines through ring closure technique as promising anticancer candidates against leukaemia and acting as selective topoisomerase II inhibitors and DNA intercalators.

In this research, two novel series of dibenzo[]azepines (14 candidates) were designed and synthesised based on the rigidification principle and following the reported doxorubicin's pharmacophoric features. The anti-proliferative activity was evaluated at the NCI against a panel of 60 cancer cell lines. Further, the promising candidates () were evaluated for their ability to inhibit topoisomerase II, where was noticed to be the most active congener.

Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline-Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors.

A series of quinoline-uracil hybrids () has been rationalized and synthesized. The inhibitory activity against hCA isoforms I, II, IX, and XII was explored. Compounds demonstrated powerful inhibitory activity against all tested hCA isoforms.

Lipid polymer hybrid nanocarriers as a combinatory platform for different anti-SARS-CoV-2 drugs supported by computational studies.

The COVID-19 pandemic caused by SARS-CoV-2 has demonstrated the potential of emergent pathogens to severely damage public health and global economies. As a consequence of the pandemic, millions of people have been forced into self-isolation, which has negatively affected the global economy. More efforts are needed to find new innovative approaches that could fundamentally change our understanding and management of this disaster.

Structure- and Ligand-Based Studies towards the Repurposing of Marine Bioactive Compounds to Target SARS-CoV-2.

This work was a structured virtual screening for marine bioactive compounds with reported antiviral activities which were subjected to structure-based studies against SARS-CoV-2 co-crystallized proteins. The molecular docking of marine bioactive compounds against the main protease (M, PDB ID: 6lu7 and 6y2f), the spike glycoprotein (PDB ID: 6vsb), and the RNA polymerase (PDB ID: 6m71) of SARS-CoV-2 was performed. Ligand-based approach with the inclusion of rapid overlay chemical structures (ROCS) was also addressed in order to examine the probability of these marine compounds sharing relevance and druggability with the reported drugs.

Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Fluorinated Candidates as PI3K Inhibitors: Targeting Fluorophilic Binding Sites.

Highly fluorinated candidates containing anticancer pharmacophores like thiosemicarbazone (-) and its cyclic analogues hydrazineylidenethiazolidine (-), 2-aminothiadiazole (-), and 2-hydrazineylidenethiazolidin-4-one (-) were synthesized, and their cytotoxic activity was assayed against 60 tumor cell lines. Compounds , , and displayed the most potent activity with lower toxic effects on MCF-10a. phosphatidylinositol 3-kinase (PI3K) enzyme inhibition was performed.

Enantioselective Separation of Chiral N1-Substituted-1-pyrazoles: Greenness Profile Assessment and Chiral Recognition Analysis.

Two commercialized polysaccharide-based chiral stationary phases, Lux cellulose-2 and Lux amylose-2, were examined for their chiral recognition ability on a set of 18 biologically active racemic 4,5-dihydro-1-pyrazole derivatives by applying normal and polar organic elution modes. The results showed that all compounds were baseline-resolved with at least one of the used elution modes. The cellulose-based column was superior using polar organic mobile-phase compositions with analysis times close to 5 min and resolutions up to 18, while the enantiomer-resolving ability of amylose-based columns was greater using the normal elution mode with analysis times close to 30 min and resolutions up to 30.

Design, synthesis, biological evaluation, and computational studies of novel thiazolo-pyrazole hybrids as promising selective COX-2 inhibitors: Implementation of apoptotic genes expression for ulcerogenic liability assessment.

A novel series of thiazolo-pyrazole hybrids has been prepared and assessed for their in vitro COX-1/COX-2 inhibitory activity. Compound 6c exhibited the most selective COX-2 inhibition profile (SI of 264) not far of Celecoxib (294). In-vivo anti-inflammatory activity revealed that compound 6d exhibited the highest activity (97.

Chirobiotic V Versus Chiralpak ID for the Enantioselective Chromatographic Separation of Chloroquine: Stability and Validation Study.

Chloroquine is a chiral antimalarial drug and demonstrates enantioselective pharmacodynamic and pharmacokinetic properties. However, this drug is administered as racemate. The knowledge of stereoselective aspects of these agents may be useful to better understand their mechanisms of action and to optimize their safety and/or clinical efficacy.

Polar solvent effects on tartaric acid binding by aromatic oligoamide foldamer capsules.

Aromatic oligoamide sequences able to fold into single helical capsules were functionalized with two types of side chains to make them soluble in various solvents such as chloroform, methanol or water and their propensity to recognize tartaric acid was evaluated. The binding affinities to tartaric acid and binding thermodynamics in different media were investigated by variable temperature (1)H NMR and ITC experiments, the two methods giving consistent results. We show that tartaric acid binding mainly rests on enthalpically favourable polar interactions that were found to be sufficiently strong to be effective in the presence of a polar aprotic solvent (DMSO) and even in pure methanol.

Enantiopure dihalocyclopropyl alcohols and esters by lipase catalyzed kinetic resolution.

Four halogenated cyclopropane derivatives with a side chain containing a primary (1 and 2) or secondary (3 and 4) alcohol moiety were subject to kinetic resolution catalyzed by lipases. Two of them containing secondary alcohol groups gave excellent results with Candida antarctica lipase B with E-values around 1000. Two enantiopure alcohols and two enantiopure butanoates are described: (1S,1'S)-1-(2',2'-dichloro-3',3'-dimethylcyclopropyl) ethanol (3), the corresponding (1R,1'R)-butanoate (3b) and (1S,1'S)-1-(1'-methyl-2',2'-dibromocyclopropyl) ethanol (4) and the corresponding (1R,1'R)-butanoate (4b).