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Ultrasonics Sonochemistry Nov 2022The chemotype of arylsulfonamide derivatives of cyclic arylguanidines is a source of molecules with valuable biological activities, including antimicrobial and antitumor...
The chemotype of arylsulfonamide derivatives of cyclic arylguanidines is a source of molecules with valuable biological activities, including antimicrobial and antitumor properties. The methods of the synthesis presented in the literature are characterized with low selectivity and high environmental nuisance. In this publication, we present a developed alternative and earlier undescribed pathway C, for the synthesis of arylsulfonamide derivatives of cyclic arylguanidines (N-(1H-arylimidazol-2-yl)arylsulfonamides and N-(1,4-dihydroquinazolin-2-yl)arylsulfonamides), including reaction between 2-(methylsulfanyl)-benzimidazole or 2-(methylsulfanyl)-3,4-dihydroquinazoline with arylsulfonamides. We also optimized previously reported methods; A (reaction of 2-aminobenzimidazole or 2-amino-3,4-dihydroquinazoline with arylsulfonyl chlorides) and B (reaction of dimethyl-(arylsulfonyl)carbonodithioimidate with aryldiamines). The conducted research allowed achieving two independent ecological and quick methods of obtaining the desired products. We used ecological methods of ultrasound-assisted or microwave synthesis, solvent-free reactions and a"green" reaction environment. In both pathways, it has proven advantageous to use HO as the solvent and KCO (1 or 3 equivalent) as the basic agent. In the sonochemical variant, the efficiency reached B: 37-89 %, C: 90 % in 60 min (P = 80 W and f = 40 kHz), while in the microwave synthesis it was B: 38-74 %, C: 63-85 % in 0.5-4 min (P = 50 W). Path A led to a complementary substitution product (i.e. 1-(arylsulfonyl)-1H-benzimidazol-2-amine or 1-(arylsulfonyl)-1,4-dihydroquinazolin-2-amine). We obtained a small group of compounds that were tested for cytotoxicity. The 10f (N-(1,4-dihydroquinazolin-2-yl)naphthalene-1-sulfonamide) showed cytotoxic activity towards human astrocytoma cell line 1321 N1. The calculated IC value was 8.22 µM at 24 h timepoint (doxorubicin suppressed 1321 N1 cell viability with IC of 1.1 µM). The viability of the cells exposed to 10f for 24 h dropped to 48.0 % compared to vehicle control, while the cells treated with doxorubicin experienced decline to 47.5 %. We assessed its potential usefulness in pharmacotherapy in the ADMET study, confirming its ability to cross the blood-brain barrier (Pe = 5.0 ± 1.5 × 10 cm/s) and the safety of its potential use in terms of DDI and hepatotoxicity.
Topics: Humans; Sulfonamides; Antineoplastic Agents; Cell Survival; Sulfanilamide; Doxorubicin; Structure-Activity Relationship; Cell Line, Tumor; Molecular Structure
PubMed: 36183548
DOI: 10.1016/j.ultsonch.2022.106165 -
Molecules (Basel, Switzerland) Nov 2022The extensive use of sulfonamides seriously threatens the safety and stability of the ecological environment. Developing green inexpensive and effective adsorbents is...
The extensive use of sulfonamides seriously threatens the safety and stability of the ecological environment. Developing green inexpensive and effective adsorbents is critically needed for the elimination of sulfonamides from wastewater. The non-modified biochar exhibited limited adsorption capacity for sulfonamides. In this study, the attapulgite-doped biochar adsorbent (ATP/BC) was produced from attapulgite and rice straw by calcination. Compared with non-modified biochar, the specific surface area of ATP/BC increased by 73.53−131.26%, and the average pore width of ATP/BC decreased 1.77−3.60 nm. The removal rates of sulfadiazine and sulfamethazine by ATP/BC were 98.63% and 98.24%, respectively, at the mass ratio of ATP to rice straw = 1:10, time = 4 h, dosage = 2 g∙L−1, pH = 5, initial concentration = 1 mg∙L−1, and temperature = 20 °C. A pseudo-second-order kinetic model (R2 = 0.99) and the Freundlich isothermal model (R2 = 0.99) well described the process of sulfonamide adsorption on ATP/BC. Thermodynamic calculations showed that the adsorption behavior of sulfonamides on the ATP/BC was an endothermic (ΔH > 0), random (ΔS > 0), spontaneous reaction (ΔG < 0) that was dominated by chemisorption (−20 kJ∙mol−1 > ΔG). The potential adsorption mechanisms include electrostatic interaction, hydrogen bonding, π−π interaction, and Lewis acid−base interactions. This study provides an optional material to treat sulfonamides in wastewater and groundwater.
Topics: Adsorption; Sulfonamides; Wastewater; Water Pollutants, Chemical; Sulfanilamide; Oryza; Adenosine Triphosphate
PubMed: 36432176
DOI: 10.3390/molecules27228076 -
Molecules (Basel, Switzerland) Sep 2022-(Aminoalkyl)azabicyclo[3.2.2]nonanes possess antiplasmodial and antitrypanosomal activity. A series with terminal tetrazole or sulfonamido partial structure was...
-(Aminoalkyl)azabicyclo[3.2.2]nonanes possess antiplasmodial and antitrypanosomal activity. A series with terminal tetrazole or sulfonamido partial structure was prepared. The structures of all new compounds were confirmed by NMR and IR spectroscopy and by mass spectral data. A single crystal structure analysis enabled the distinction between isomers. The antiprotozoal activities were examined in vitro against strains of and (STIB 900). The most active sulfonamide and tetrazole derivates showed activities in the submicromolar range.
Topics: Alkanes; Antimalarials; Antiprotozoal Agents; Parasitic Sensitivity Tests; Plasmodium falciparum; Sulfanilamide; Sulfonamides; Tetrazoles; Trypanosoma brucei rhodesiense
PubMed: 36234752
DOI: 10.3390/molecules27196217 -
BMC Infectious Diseases Nov 2023As an opportunistic pathogen, Nocardia often occurring in the immunocompromised hosts. As the unspecifc clinical presentation and low identification rate of the culture...
OBJECTIVE
As an opportunistic pathogen, Nocardia often occurring in the immunocompromised hosts. As the unspecifc clinical presentation and low identification rate of the culture dependent methods, Nocardia infection may be under-diagnosis. Recent study have reported physicians could benefit from metagenomic next-generation sequencing (mNGS) in Nocardia diagnosis. Herein, we present patients with a positive detection of nocardiosis in mNGS, aiming to provide useful information for an differential diagnosis and patients management.
METHODS
A total of 3756 samples detected for mNGS from March 2019 to April 2022 at the Fifth Affifiliated Hospital of Sun Yat-sen University, were screened. Clinical records, laboratory finding, CT images and mNGS results were reviewed for 19 patients who were positive for Nocardia genus.
RESULTS
Samples from low respiratory tract obtained by bronchoscope took the major part of the positive (15/19). 12 of 19 cases were diagnosis as Nocardiosis Disease (ND) and over half of the ND individuals (7/12) were geriatric. Nearly all of them (10/12) were immunocompetent and 2 patients in ND group were impressively asymptomatic. Cough was the most common symptom. Nocardia cyriacigeorgica (4/12) was more frequently occurring in ND, followed by Nocardia abscessus (3/12). There are 3 individuals detected more than one kind of Nocardia species (Supplementary table 1). Except one with renal failure and one allergic to sulfamethoxazole, all of them received co-sulfonamide treatment and relieved eventually.
CONCLUSION
Our study deciphered the clinical features of patients with positive nocardiosis detected by mNGS. Greater attention should be paid to the ND that occurred in the immunocompetent host and the geriatric. Due to the difficulties in establishing diagnosis of Nocardiosis disease, mNGS should play a much more essential role for a better assessment in those intractable cases. Co-sulfonamide treatment should still be the first choice of Nocardiosis disease.
Topics: Humans; Aged; Tertiary Care Centers; High-Throughput Nucleotide Sequencing; Nocardia; Nocardia Infections; Sulfamethoxazole; Sulfanilamide; China
PubMed: 37940842
DOI: 10.1186/s12879-023-08615-z -
Journal of Enzyme Inhibition and... Dec 2023A novel library of human carbonic anhydrase (hCA) inhibitors based on the 2-sulfanilamido[1,2,4]triazolo[1,5-]pyrimidine skeleton modified at its 7-position was prepared...
Design, synthesis, and biological investigation of selective human carbonic anhydrase II, IX, and XII inhibitors using 7-aryl/heteroaryl triazolopyrimidines bearing a sulfanilamide scaffold.
A novel library of human carbonic anhydrase (hCA) inhibitors based on the 2-sulfanilamido[1,2,4]triazolo[1,5-]pyrimidine skeleton modified at its 7-position was prepared by an efficient convergent procedure. These derivatives were evaluated for their inhibition properties against a representative panel of hCA isoforms (hCA I, II, IV, IX, and XII). The target tumour-associated isoforms hCA IX and XII were potently inhibited with s in the low nanomolar range of 5-96 nM and 4-72 nM, respectively. Compounds , , , and were the most potent hCA IX inhibitors with s of 5.1, 8.6, 4.7, and 5.1 nM, respectively. Along with derivatives and , compounds and potently inhibited hCA XII isoform with s in a single-digit nanomolar range of 8.8, 5.4, 4.3, and 9.0 nM, respectively. Compounds , , and exhibited the best selectivity against hCA IX and hCA XII isoforms over off-target hCA II, with selectivity indexes ranging from 5 to 14.
Topics: Humans; Carbonic Anhydrase II; Structure-Activity Relationship; Carbonic Anhydrase IX; Antigens, Neoplasm; Carbonic Anhydrase I; Protein Isoforms; Sulfanilamides; Carbonic Anhydrase Inhibitors; Molecular Structure
PubMed: 37850364
DOI: 10.1080/14756366.2023.2270180 -
Journal of Enzyme Inhibition and... Dec 2022The almost empty armamentarium to treat schistosomiasis, a neglected parasitic disorder caused by trematode flatworms of the genus , except Praziquantel (PZQ), urged to...
The almost empty armamentarium to treat schistosomiasis, a neglected parasitic disorder caused by trematode flatworms of the genus , except Praziquantel (PZQ), urged to find new alternatives to fight this infection. Carbonic Anhydrase from (SmCA) is a possible new target against this nematode. Here, we propose new PZQ derivatives bearing a primary sulphonamide group in order to obtain hybrid drugs. All compounds were evaluated for their inhibition profiles on both humans and Schistosoma CAs, X-ray crystal data of SmCA and hCA II in adduct with some inhibitors were obtained allowing the understanding of the main structural factors responsible of activity. The compounds showed inhibition of immature and adult , but further optimisation is required for improved activity.
Topics: Animals; Carbonic Anhydrases; Humans; Praziquantel; Schistosoma mansoni; Schistosomicides; Sulfanilamide; Sulfonamides
PubMed: 35635137
DOI: 10.1080/14756366.2022.2078970 -
The Journal of Veterinary Medical... Jul 2016The oral pharmacokinetics of three sulfonamides, sulfadimidine (pKa 7.5), sulfadiazine (pKa 6.5) and sulfanilamide (pKa 10.5), with different rates of unionization in... (Comparative Study)
Comparative Study
The oral pharmacokinetics of three sulfonamides, sulfadimidine (pKa 7.5), sulfadiazine (pKa 6.5) and sulfanilamide (pKa 10.5), with different rates of unionization in rumen juice, were compared in Shiba goats to clarify the relationship between drug absorption profiles after their oral administration as well as their degree of unionization in the rumen. Sulfonamides were administered either into the left jugular vein or orally to five male goats at doses of 10 mg/kg body weight, using a crossover design with at least a 3-week washout period. The Tmax of sulfadimidine, sulfadiazine and sulfanilamide reached 2.0 ± 1.2, 6.0 ± 0.0, and 7.8 ± 1.6 hr, respectively, after their oral administration, and this was followed by their slow elimination due to a slow rate of drug absorption from the gastrointestinal tract. The MAT and t1/2ka of sulfadiazine (13.2 ± 2.0 and 10.9 ± 1.08 hr) were significantly longer than those of sulfanilamide (9.09 ± 1.67 and 7.46 ± 1.70 hr) and sulfadimidine (7.52 ± 0.85 and 5.17 ± 0.66 hr). These results suggest that the absorption rates of highly unionized drugs (such as sulfanilamide and sulfadimidine) from the forestomach of goats may be markedly higher than less unionized ones (such as sulfadiazine). The mean oral bioavailability of sulfadiazine was high (83.9 ± 17.0%), whereas those of sulfadimidine and sulfanilamide were low (44.9 ± 16.4% and 49.2 ± 2.11%, respectively).
Topics: Administration, Oral; Animals; Anti-Infective Agents; Goats; Injections, Intravenous; Male; Sulfadiazine; Sulfamethazine; Sulfanilamide; Sulfanilamides
PubMed: 27010464
DOI: 10.1292/jvms.15-0601 -
The Journal of Physical Chemistry. B Aug 2023Antibiotics play a key role in the fight against bacterial diseases. However, bacteria quickly learn how to minimize the effects of antibiotics and strengthen their...
Antibiotics play a key role in the fight against bacterial diseases. However, bacteria quickly learn how to minimize the effects of antibiotics and strengthen their resistance. Thus, the fight against them becomes more and more difficult and there is a constant search for new bactericidal compounds. It is important in this type of search to determine the basic properties of compounds such as p, hydrogen bond formation, or hydrophobicity. Here, we present the results of our in silico study of five sulfonamide derivatives differing in alkylamine substituent length. Based on our results, we propose a model of three possible p values for each of the studied compounds. Interestingly, the use of Muckerman's approach for p determination exhibits that theoretical and experimental results are in very good agreement. Intramolecular hydrogen bond formation affects p. The strength of the H-bond interaction increases from ethyl to butylamine and then decreases with the elongation of the alkylamine chain. The obtained partition coefficients (expressed here in the value of log ) increase with the number of carbon atoms in the alkylamine chain following Lipinski's rule of five. The presented results provide important structural, physicochemical, and thermodynamic information that allows for the understanding of the influence of some sulfonamides and their possible activity.
Topics: Sulfonamides; Models, Theoretical; Sulfanilamide; Anti-Bacterial Agents
PubMed: 37478052
DOI: 10.1021/acs.jpcb.3c01965 -
Molecules (Basel, Switzerland) Oct 2022Diabetes mellitus is a chronic metabolic disorder in which the pancreas secretes insulin but the body cells do not recognize it. As a result, carbohydrate metabolism...
Diabetes mellitus is a chronic metabolic disorder in which the pancreas secretes insulin but the body cells do not recognize it. As a result, carbohydrate metabolism causes hyperglycemia, which may be fatal for various organs. This disease is increasing day by day and it is prevalent among people of all ages, including young adults and children. Acarbose and miglitol are famous alpha-glucosidase inhibitors but they complicate patients with the problems of flatulence, pain, bloating, diarrhea, and loss of appetite. To overcome these challenges, it is crucial to discover new anti-diabetic drugs with minimal side effects. For this purpose, benzotriazinone sulfonamides were synthesized and their structures were characterized by FT-IR, H-NMR and C-NMR spectroscopy. alpha-glucosidase inhibition studies of all synthesized hybrids were conducted using the spectrophotometric method. The synthesized compounds revealed moderate-to-good inhibition activity; in particular, nitro derivatives and were found to be the most effective inhibitors against this enzyme, with IC values of 32.37 ± 0.15 µM and 37.75 ± 0.11 µM. In silico studies, including molecular docking as well as DFT analysis, also strengthened the experimental findings. Both leading compounds and showed strong hydrogen bonding interactions within the enzyme cavity. DFT studies also reinforced the strong binding interactions of these derivatives with biological molecules due to their lowest chemical hardness values and lowest orbital energy gap values.
Topics: Child; Humans; Glycoside Hydrolase Inhibitors; alpha-Glucosidases; Molecular Docking Simulation; Acarbose; Sulfonamides; Spectroscopy, Fourier Transform Infrared; Structure-Activity Relationship; Diabetes Mellitus; Sulfanilamide; Insulins; Molecular Structure
PubMed: 36296403
DOI: 10.3390/molecules27206783 -
The Journal of Pediatrics Jan 2018
Topics: Child; Clinical Trials as Topic; Drug Development; Drug Labeling; Guidelines as Topic; Humans; Patient Participation; Pediatrics; Sulfanilamide; Thalidomide; United States; United States Food and Drug Administration
PubMed: 28942898
DOI: 10.1016/j.jpeds.2017.08.011