Effect of Magnesium on Ventricular Extrasystoles in Children.

Magnesium (Mg) is a crucial element for cardiovascular system and its deficiency results in a variety of cardiac arrhythmias. The aim of this study is to determine the effect of oral Mg supplementation on the frequency of ventricular extrasystoles (VES) in children. Magnesium supplementation was given to 42 children who had VES without structural heart disease. Clinical, electrocardiographic, and Holter monitoring studies were reviewed. The mean baseline 24 h VES burden on Holter monitoring was 10.26% ± 4.13% and it was decreased to 6.62% ± 3.88% after. There was no significant difference between the pre-treatment serum Mg levels and the decrease in the frequency of VES. In conclusion, oral Mg therapy was found to be effective at suppressing VES in children regardless of serum Mg levels. Large and randomized studies are needed to demonstrate the effect of magnesium on VES suppression.

Ventricular Extrasystole in Children: Single-Center Experience.

OBJECTIVE: Ventricular extrasystole is one of the most common rhythm disorders in children, and almost all of them are characterized by normal cardiac functions without structural cardiac abnormalities. The aim of this study was to assess the clinical course of ventricular extrasystole in children who did not have cardiac structural abnormalities. MATERIALS AND METHODS: This retrospective study analyzed 24-hour rhythm Holter recordings performed in our clinic in children. Patients diagnosed with isolated ventricular extrasystole in Holter records and without structural heart disease on echocardiography were included in the evaluation. RESULTS: A total of 20 160 Holter results were evaluated in the study, and 226 patients (male; 66%) met the criteria. The mean follow-up time was 8.7 ± 3.2 years. While 81.8% of the patients were asymptomatic, the most common symptom was palpitation and 5 patients had syncope. Of the patients, 72 (31.8%) received medical therapy. Beta-blockers were the most often pre- scribed medication. Cardiomyopathy did not develop in any of the patients during the follow- up period. A partial reduction in the frequency of ventricular extrasystole was observed in 42% of the patients, while complete recovery was observed in 22%. CONCLUSION: Ventricular extrasystole in children generally has a good prognosis; most of them are asymptomatic, and the rates of spontaneous regression over time are quite high, regard- less of the origin.

A rare and fatal cause of hypertrophic cardiomyopathy: Danon disease.

Danon disease is a rare and fatal disease caused by a mutation in the lysosome-associated membrane protein 2 gene. Impaired intracellular autophagy causes lysosomal vacuoles to accumulate mainly in myocardial and skeletal muscle cells, leading to hypertrophic cardiomyopathy, skeletal myopathy, and varying degrees of intellectual disability. Two distinct childhood presentations of Danon disease are described in this report.

The Role of External Loop Recorders in Arrhythmia-Related Symptoms in Children: A Single Center Experience.

In this study, we report our experience with the use of external loop recorders (ELRs), in terms of diagnostic efficiency according to symptoms and symptom-rhythm correlation in pediatric patients. We evaluated ELRs applied to 178 patients between April 2017 and November 2020 at our center. The mean age of 172 patients included in the study was 13.6 ± 3.8 years, and 69.8% were female. ELR indications were palpitations in 98 (56.9%) cases, chest pain and palpitations in 43 (25%) cases, presyncope/syncope in 28 (16.2%) cases, and pacemaker/ implantable cardioverter-defibrillator (ICD) problems in 3 (0.2%) cases. ELR recording times were 14.2 ± 9.7 days on average, ranging from 2 to 67 days. While the symptom-rhythm correlation was 29.1% in total, when the indications were evaluated one by one, this correlation was found to be 30.2% in palpitations, 34.7% in chest pain and palpitations, and 10.7% in presyncope/syncope. The total diagnostic efficiency was 68.1%. In the follow-up of ELR cases, a total of 139 (80.8%) patients received clinical follow-up without medication, 15 (8.8%) patients received medical treatment, and 18 (10.4%) patients underwent EPS. The cardiac ELR system is useful in detecting underlying arrhythmias. Demonstrating sinus tachycardia at the time of the symptom may be seen as negative finding, but while experiencing symptoms, it is diagnostically valuable and may help avoid further investigation with costly and invasive diagnostic procedures. For diagnostic efficiency and cost effectiveness, the optimal recording time is 2 weeks, but it should be extended to 4 weeks in cases such as of presyncope/syncope that cannot be explained with a 2-week ELR use.

Synthesis, characterization, in vitro cytotoxicity and antimicrobial investigation and evaluation of physicochemical properties of novel 4-(2-methylacetamide)benzenesulfonamide derivatives.

In this study, several sulfonamide derivatives, 4-(2-methylacetylamino)benzenesulfonamides were synthesized. Chemical structures of the derivatives were characterized by 1H NMR, 13C NMR, LC-MS-MS, UV-Vis, FTIR, photoluminescence and elemental analysis. Sulfanilamide was reacted with 2-bromopropionyl bromide, in the presence of pyridine, to form bromo-substituted sulfonamide key intermediates, which were subsequently treated with secondary amines to obtain novel sulfonamide derivatives. All the synthesized compounds were evaluated for in vitro antimicrobial activities and cytotoxicity. Increases in ring size, and rings bearing a nitrogen heteroatom led to improvements in antimicrobial activities. As the presence of CA IX and CA XII enzymes have been implicated in some cancerous tumors, the studies presented herein focuses on targeting these enzymes. It was found that the synthesized derivatives had in vitro anti-cancer properties, where compounds (3-6) were found to be active against all cancerous cells, and no cytotoxic effects on normal cells were observed.

Synthesis of 4-sulfamoylphenyl-benzylamine derivatives with inhibitory activity against human carbonic anhydrase isoforms I, II, IX and XII.

Imine derivatives were obtained by condensation of sulfanilamide with substituted aromatic aldehydes. The Schiff bases were thereafter reduced with sodium borohydride, leading to the corresponding amines, derivatives of 4-sulfamoylphenyl-benzylamine. These sulfonamides were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). We noted that the compounds incorporating secondary amine moieties showed a better inhibitory activity against all CA isozymes compared to the corresponding Schiff bases. Low nanomolar CA II, IX and XII inhibitors were detected, whereas the activity against hCA I was less potent. The secondary amines incorporating sulfonamide or similar zinc-binding groups, poorly investigated chemotypes for designing metalloenzyme inhibitors, may offer interesting opportunities in the field due to the facile preparation and possibility to explore a vast chemical space.

Synthesis of Schiff base derivatives of 4-(2-aminoethyl)-benzenesulfonamide with inhibitory activity against carbonic anhydrase isoforms I, II, IX and XII.

Schiff base derivatives were obtained by reaction of 4-(2-aminoethyl)benzenesulfonamide with aromatic aldehydes. The corresponding secondary amine derivatives were also prepared by reduction of the imine compounds with NaBH4. These derivatives were investigated as inhibitors of four human carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic isozymes hCA I and II, as well as, the transmembrane, tumor-associated hCA IX and XII. Some of the newly synthesised compounds showed effective inhibitory activities against these CA isozymes. Many low nanomolar inhibitors were detected against all isoforms among the secondary amines whereas the Schiff bases were by far less active compared to the corresponding reduced derivatives among all investigated isoforms.

4-{[4-(Di-methyl-amino)-benzyl-idene]amino}-benzene-sulfonamide.

The title Schiff base compound, C15H17N3O2S, is non-planar with a dihedral angle of 69.88 (4)° between the planes of the benzene rings. In the crystal, pairs of N-H⋯N hydrogen bonds, between the sulfonamide nitro-gen-H atom and the azomethine N atom, link the mol-ecules into inversion dimers, forming R 2 (2)(16) ring motifs. These dimers are linked by N-H⋯O hydrogen bonds, between the sulfonamide nitro-gen-H atom and one sulfonamide O atom, forming sheets lying parallel to (100). Within the sheets there are weak parallel slipped π-π inter-actions involving inversion-related benzene-sulfonamide rings [centroid-centroid distance = 3.8800 (9) Å; normal distance = 3.4796 (6) Å; slippage = 1.717 Å].

4-(3-Chloro-2,2-dimethyl-propanamido)-benzene-sulfonamide.

In the title compound, C11H15ClN2O3S, the 3-chloro-2,2-dimethyl-propanamide and sulfonamide substituents are arranged on opposite sides of the benzene ring plane. In the crystal, mol-ecules are linked by N-H⋯O and C-H⋯O hydrogen bonds, forming a three-dimensional network.

4-(5-Chloro-penta-namido)-benzene-sulfonamide.

The mol-ecular conformation of the title compound, C11H15ClN2O3S, is stabilized by a C-H⋯O hydrogen bond, forming an S(6) ring motif. In the crystal, mol-ecules are linked by two pairs of inversion-related N-H⋯O hydrogen bonds, generating R2(2)(8) and R2(2)(20) ring motifs, resulting in chains running along [0-11]. These chains are connected by N-H⋯O hydrogen bonds along [100], forming layers parallel to (011). There are also C-H⋯π inter-actions between the layers, which consolidate the three-dimensional structure.

4-[3-(4-Methyl-piperidin-1-yl)propan-amido]-benzene-sulfonamide monohydrate.

In the title compound, C15H23N3O3S·H2O, the piperidine ring has a chair conformation. In the crystal, the sulfonamide mol-ecules are linked by N-H⋯O hydrogen bonds, forming a layer parallel to (10-1). The layers are inter-connected via N-H⋯Ow, Ow-H⋯N and Ow-H⋯O (w = water) hydrogen bonds, forming a three-dimensional network.

Synthesis of sulfanilamide derivatives and investigation of in vitro inhibitory activities and antimicrobial and physical properties.

Novel sulfanilamide derivatives were synthesized and evaluated for carbonic anhydrase inhibitory activity as a target for the treatment of glaucoma, and antibacterial properties for use in chemotherapy. Synthesized compounds were characterized by FT-IR, (1)H NMR, (13)C NMR and photoluminescence. In vitro inhibitory activities were measured by UV-Vis and some of the compounds were found have greater inhibitory effects than the lead compound sulfanilamide. The correlation between inhibitory activity, biological properties and the physicochemical properties of water solubility and partition coefficients was also investigated. Sulfanilamide derivatives gave intense emissions upon irradiation by UV light and a dimethyl substituted compound and a cyclic analog have photoluminescence quantum yields 42% and 31% and long excited-state lifetimes of 3.92 and 2.91 ns, respectively.

3-Chloro-N-(4-sulfamoylphen-yl)propanamide.

In the title compound, C(9)H(11)ClN(2)O(3)S, the dihedral angle between the benzene ring and the amido -NHCO- plane is 15.0 (2)°. An intra-molecular C-H⋯O hydrogen bond generates an S(6) ring motif. In the crystal structure, the amino NH(2) group is involved in inter-molecular N-H⋯O hydrogen bonds, which connect the mol-ecules into a double layer structure expanding parallel to the bc plane. The layers are further linked by an amido N-H⋯O hydrogen bond. Between the layers, a weak π-π inter-action with a centroid-centroid distance of 3.7447 (12) Šis also observed.

2-Chloro-N-(4-sulfamoylphen-yl)acetamide.

In the title compound, C(8)H(9)ClN(2)O(3)S, the benzene ring makes a dihedral angle of 4.1 (9)° with the amido -NHCO- plane including the major occupancy component of the carbonyl O atom [19 (4)° for the minor component]. An intra-molecular C-H⋯O inter-action occurs. The O atom of the carbonyl group is disordered over two positions with site-occupancy factors of 0.67 (11) and 0.33 (11). Inter-molecular N-H⋯O hydrogen bonds help to stabilize the crystal structure.

Synthesis, spectroscopy, X-ray structure and redox behaviors of 4-(N-R-salicylideneimine)-2,6-diphenylphenols.

A series of sterically hindered 4-(N-R-salicylaldimine)-2,6-diphenylphenols (X), where R=H (1), 3-CH3 (2), 5-CH3 (3), 3-OCH3 (4), 4-OCH3 (5), 5-OCH3 (6), 3-tBu (7), 5-tBu (8), 3,5-tBu2(9) and 5,6-benzo(10), were synthesized and their structure as well as redox behavior studied by analytical, spectroscopic [1H, (13C) NMR, IR, UV-vis and mass spectrometry] and cyclic voltammetric (CV) techniques. Single crystal X-ray diffraction studies of 7 evidenced its existence as non-planar enol-imine tautomer structure, in which the phenol ring of the molecule is twisted around C-N single bond by 21.5(2) degrees. The packing structure of 7 is stabilized by C-H...pi(Ph) and O...O and C...O intermolecular short contact interactions. The CV of X display rate is dependent on irreversible and quasi-reversible redox waves in the anodic and cathodic regions due to oxidation and reduction of phenolic and iminic groups, respectively. As evidenced by ESR and UV-vis study, chemical oxidation of X by PbO2 and (NH4)2Ce(NO3)6 in MeCN and CHCl3 generates stable phenoxyl radicals [(g approximately 2.005 and lambda approximately 450 nm (1600-8200 M(-1) cm(-1))].

A DFT-based quantum theoretic QSAR study of aromatic and heterocyclic sulfonamides as carbonic anhydrase inhibitors against isozyme, CA-II.

In this study, DFT/B3LYP level of theory with the 6-31G (d) basis set, was used to calculate a set of molecular descriptors of 30 sulfonamide compounds with carbonic anhydrase inhibitory activity. Quantitative structure-activity relationship (QSAR) models of the biological activity (K(i)) of 30 inhibitors of carbonic anhydrase (CA-II) were established using some of the following calculated quantum mechanical descriptors, dipole moment (mu), average polarizability (P), ionization potential (I), electron affinity (A), LUMO energy (epsilon(LUMO)), HOMO energy (epsilon(HOMO)), total energy at 0K (Te), entropy at 298K (S), electronegativity (chi), hardness (eta), electrophilicity (omega), and differences between HOMO and LUMO energies (epsilon(H)-epsilon(L)). The QSAR models obtained by employing multiple linear regression techniques are aimed at correlating the structures to their reported experimental inhibitory activity values, K(i). Among the models presented in this study, statistically the most significant one is a four-parameter linear equation with correlation coefficient, R(2) values of ca. 0.847 and the cross-validated correlation coefficient, R values of ca. 0.775. This study also reconstructed the obtained models using AM1-based calculated descriptors to demonstrate the superiority of DFT over AM1 for quantum calculations of mechanical descriptors. The results are discussed in the light of the main factors that influence the inhibitory activity of carbonic anhydrase (CA-II) isozyme.

Synthesis of alpha-fluoro- and alpha,alpha-difluoro-benzenemethanesulfonamides: new inhibitors of carbonic anhydrase.

Direct fluorination of arenemethanesulfonamide anions under mild conditions and in high yield has been accomplished using N-fluorobisbenzenesulfonimide, NFSi, on carbanions of N-tert-butyl- and N-bis-(4-methoxyphenyl-methyl)-benzenemethanesulfonamides giving novel alpha-fluoro- and alpha,alpha-difluoro-benzenemethanesulfonamides respectively: IC(50) and pK(a) data show that alpha-halogenation enhances sulfonamide acidity incrementally and correlates well with increased carbonic anhydrase inhibition, while lipophilicity is also enhanced.

Carbonic anhydrase inhibitors. Novel sulfanilamide/acetazolamide derivatives obtained by the tail approach and their interaction with the cytosolic isozymes I and II, and the tumor-associated isozyme IX.

A series of sulfonamides has been obtained by reacting sulfanilamide or 5-amino-1,3,4-thiadiazole-2-sulfonamide with omega-chloroalkanoyl chlorides, followed by replacement of the omega-chlorine atom with secondary amines. Tails incorporating heterocyclic amines belonging to the morpholine, piperidine and piperazine ring systems have been attached to these sulfonamides, by means of an alkanoyl-carboxamido linker containing from two to five carbon atoms. The new derivatives prepared in this way were tested as inhibitors of three carbonic anhydrase (CA, EC 4.2.1.1) isozymes, the cytosolic isozymes CA I and II, and the catalytic domain of the transmembrane, tumor-associated isozyme CA IX. Several low nanomolar CA I and CA II inhibitors were detected both in the aromatic and heterocyclic sulfonamide series, whereas the best hCA IX inhibitors (inhibition constants in the range of 22-35 nM) all belonged to the acetazolamide-like derivatives.