Sulfonamide Derivatives Research Articles

Elucidation of benzene sulfonamide derivative binding at a novel interprotomer pocket of wild type and mutants of coxsackievirus B3 viral capsid using molecular dynamics simulations and density functional theory

Coxsackievirus B3 (CVB3), a serotype of enterovirus B, causes hand, foot, and mouth disease; pericarditis; and myocarditis. A benzene sulfonamide derivative is reported to have inhibitory activity against wild-type (WT) and eight mutants of the viral capsid of CVB3. Furthermore, the crystal structure of the complex formed between WT viral capsid of CVB3 and the derivative revealed binding at a novel druggable interprotomer pocket. We investigated how the compound could be a potent inhibitor of both WT and some mutants of CVB3 by determining binding to the viral capsid and the interaction energy with the binding pocket based on molecular dynamics simulations and density functional theory. We found that hydrogen bonds, pi–pi interactions, and electrostatic interactions are the key interactions with a protomer unit of CVB3 viral capsid. The residual interaction energy determined using density functional theory revealed key binding with VP1:Arg234 and a residue in the nearby VP1 unit (VP1’:Arg219). These results explain why the compound is still a potent inhibitor against eight mutants. Moreover, the decreased inhibitory activity for some mutants could be explained by the calculated binding energy and the highest occupied molecular orbital and lowest unoccupied molecular orbital energy. The results will be helpful for the development of drugs resistant to CVB3.

Potent and selective carbonic anhydrase inhibition activities of pyrazolones bearing benzenesulfonamides

This research introduces a series of fourteen 4-aryl-hydrazonopyrazolone sulfonamide derivatives, denoted as 3(a-g) and 4(a-g), which encompass various aromatic substitutions. The aim was to assess the inhibitory potential of these compounds against four significant isoforms, including the cytosolic isoforms hCA I and II, as well as the tumor-associated membrane-bound isoforms hCA IX and XII. Most of the tested compounds exhibited substantial inhibition against the tumor-associated isoform hCA IX, with Ki values spanning from 1.1 to 158.2 nM. Notably, compounds 3e and 3g showed particularly strong inhibitory activity against the tumor-associated membrane-bound isoforms, hCA IX and XII, while maintaining a high selectivity ratio over cytosolic off-target isoforms hCA I and II. This selectivity is vital due to the potential of hCA IX and hCA XII as drug targets for hypoxic tumors. In an effort to create novel analogs that exhibit enhanced carbonic anhydrase inhibitory activity and specificity, we investigated the structure–activity relationships of these compounds and provided a concise interpretation of our findings. Consequently, these compounds merit consideration for subsequent medicinal and pharmacological research, holding potential for developing novel therapeutic agents targeting specific isoforms in hypoxic tumors.

Design, synthesis and biological evaluation of triazole, sulfonamide and sulfonyl urea derivatives of N-acylhomoserine lactone as quorum sensing inhibitors

Triazole, sulfonamide and sulfonyl urea derivatives of N-acylhomoserine lactones (AHLs) have been prepared from homoserine lactone hydrobromide which in turn is derived from l-methionine. The molecules were screened against Chromobacterium violaceum ATCC 12472 for their quorum sensing inhibitory (QSI) activity. Among them, compounds 6, 7 and 14 were exhibited comparable antibacterial activities with reference to penicillin and streptomycin as 37.5 µg/mL, while compounds 7, 13 and 17 exhibited promising QSI activity. These compounds represent a synthetically accessible class of AHL analogs could find utility to improve their potency.

İMİDAZOLİNON BAZLI SÜLFONAMİD TÜREVLERİ: SENTEZ, KARAKTERİZASYON VE BAZI METABOLİK ENZİMLERE KARŞI İNHİBİTÖR ÖZELLİKLERİ

Objective: The purpose of the work was to investigate new synthetic compounds of imidazolinone-based sulfonamide derivatives as potent and selective enyzme inhibitors. A number of compounds synthesized and their inhibitory action against acetylcholine esterase (AChE), and human (h) carbonic anhydrase (CA) isoforms I and II were investigated. Material and Method: The identity of the compounds has been confirmed by HRMS, 1H NMR, and 13C NMR. The pharmacological potential of the compounds has been determined by in vitro enzyme-based assays. Result and Discussion: In this study, a series of imidazolinone-based sulfonamide derivatives were synthesized from 4-(2,4-dimethoxybenzylidene)-2-phenyloxazol-5(4H)-one, sodium acetate, glacial acetic acid, and suitable sulfonamide derivatives such as sulfaguanidine (3), sulfanilamide (4), sulfadiazine (5). These compounds showed potent inhibitory action against acetylcholine esterase (AChE), and human (h) carbonic anhydrase (CA) isoforms I and II. Compound 4 (Ki=19.53±1.23 nM) was a potent and selective inhibitor against hCA I while compound 3 (Ki=16.49±2.20 nM) was found to be potent inhibitor against hCA II. Compound 5 with Ki of 11.68±1.45 nM showed a potent inhibitory effect against the AChE enzyme. Imidazolinone-based sulfonamides can be used in the design of selective CAs inhibitors and anti-Alzheimer's compounds for further studies.

In silico research on new sulfonamide derivatives as BRD4 inhibitors targeting acute myeloid leukemia using various computational techniques including 3D-QSAR, HQSAR, molecular docking, ADME/Tox, and molecular dynamics

Acute myeloid leukemia, a serious condition affecting stem cells, drives uncontrollable myeloblast proliferation, leading to accumulation. Extensive research seeks rapid, effective chemotherapeutics. A potential option is a BRD4 inhibitor, known for suppressing cell proliferation. Sulfonamide derivatives probed essential structural elements for potent BRD4 inhibitors. To achieve this goal, we employed 3D-QSAR molecular modeling techniques, including CoMFA, CoMSIA, and HQSAR models, along with molecular docking and molecular dynamics simulations. The validation of the 2D/3D QSAR models, both internally and externally, underscores their robustness and reliability. The contour plots derived from CoMFA, CoMSIA, and HQSAR analyses played a pivotal role in shaping the design of effective BRD4 inhibitors. Importantly, our findings highlight the advantageous impact of incorporating bulkier substituents on the pyridinone ring and hydrophobic/electrostatic substituents on the methoxy-substituted phenyl ring, enhancing interactions with the BRD4 target. The interaction mode of the new compounds with the BRD4 receptor (PDB ID: 4BJX) was investigated using molecular docking simulations, revealing favorable binding energies, supported by the formation of hydrogen and hydrophobic bonds with key protein residues. Moreover, these novel inhibitors exhibited good oral bioavailability and demonstrated non-toxic properties based on ADMET analysis. Furthermore, the newly designed compounds along with the most active one from series 58, underwent a molecular dynamics simulation to analyze their behavior. The simulation provided additional evidence to support the molecular docking results, confirming the sustained stability of the analyzed molecules over the trajectory. This outcome could serve as a valuable reference for designing and developing novel and effective BRD4 inhibitors. Communicated by Ramaswamy H. Sarma

New quinazoline sulfonamide derivatives as potential anticancer agents: Identifying a promising hit with dual EGFR/VEGFR-2 inhibitory and radiosensitizing activity

Herein, we report the synthesis of a series of new quinazoline sulfonamide conjugates 2–16 and their evaluation as potential anticancer agents via dual targeting of EGFRT790M and VEGFR-2. The newly synthesized compounds were designed based on the structure requirements of the target receptors and were confirmed using spectral data. The compounds were evaluated for their cytotoxicity against four cancer cell lines (HepG2, MCF-7, HCT116 and A549) using MTT assay. The most active compounds were further evaluated for their inhibitory activity against EGFRT790M and VEGFR-2. Compound 15 showed the most significant cytotoxic activity with IC50 = 0.0977 µM against MCF-7 and the most potent inhibitory activity against both EGFR and VEGFR with IC50 = 0.0728 and 0.0523 µM, respectively. Compound 15 was able to induce apoptosis in MCF-7 cells and cell cycle arrest at the G2/M phase. The relative safety profile of 15 was assessed using HEK-293 normal cell line and an ADMET profile was carried out. Radiosensitizing evaluation of 15 proved its significant ability to sensitize the cancer cell to the effect of radiation after being subjected to a single dose of 8 Gy gamma irradiation. Molecular docking studies revealed that 15 could bind to the ATP-binding site of EGF and VEGF receptors, inhibiting their activity.

Antibacterial, Cytotoxic and Genotoxic Assessment of New Sulfonamide Derivatives.

In the last few years, the interest in sulfonamides has expanded owing to their broad spectrum of biological activities. Their flexible structure turns them into amazing candidates to replace old drugs or develop modern multi-target agents. In this study, a series of new sulfonamides (sul1-5) was evaluated, in vitro, for the antibacterial, cytotoxic and genotoxic effects. The antibacterial activity was investigated against 12 clinical and 4 reference strains. Cytotoxic activity was carried out by the brine shrimp bioassay and the genotoxicity was assessed in the Ames test. An interesting antibacterial activity was showed especially against Gram negative strains. The inhibition zones varied between 15 and 30 mm, and the Minimum Inhibitory Concentrations (MIC's) values between 0.5 and 256 μg/ml. No antibacterial activity was shown with S. aureus isolates. Only Sul1 and Sul4 were active against P. aeruginosa. Compounds Sul1 and Sul2 showed a significant cytotoxicity with LC50 equal to 18.29 and 18 μg/ml respectively, and a genotoxic effect against TA100 and TA1535 Salmonella strains. Only compounds Sul3, Sul4 and Sul5 with an interesting antibacterial activity, no cytotoxicity and no genotoxic effects, could be exploited against resistant pathogens as new drugs.

Sulfonamide Derivatives as Novel Surfactant/Alkaline Flooding Processes for Improving Oil Recovery.

Over time, oil consumption has increased along with a continuous demand for petroleum products that require finding ways to increase hydrocarbon production more economically and effectively. So, enhanced oil recovery technologies are believed to be very promising and will serve as a key to meeting the future energy demand. This paper aims to introduce an innovative method to boost the EOR by using two novel types of surfactants synthesized from sulfonamide derivatives. Types I and II surfactants were analyzed using Fourier transform infrared spectroscopy, and their characterization was further performed using 1H NMR and 13C NMR spectroscopy. Additionally, the evaluation of these surfactants included interfacial tension measurements at concentrations up to 0.9 wt %. The combination of types I and II surfactants with alkaline (NaOH) was also investigated by the measurements of interfacial tension. A series of coreflood and sandpack tests under high-salinity conditions were carried out to assess the effects of a surfactant alone and alkaline-surfactant as a combination on improving oil recovery. The rock wettability was evaluated using relative permeability saturation curves, and the oil displacement efficiency was determined using fractional flow curves. The coreflood results demonstrated that alkaline-surfactant flooding with the chemical formula 0.2 wt % surfactant type II plus 0.5 wt % NaOH achieved a higher oil recovery of 74% OOIP compared to surfactant flooding with the chemical formula 0.5 wt % surfactant type II (64% OOIP) and waterflooding (saline solution with a 35,000 ppm salinity: 48% OOIP). Moreover, the experimental results showed that under both core and sandpack flood conditions, there was a noticeable reduction in oil-water interfacial tension, a change in rock wettability to more water-wet, and higher efficiency of oil displacement when alkaline was added to the surfactant. Based on current research, the alkaline-surfactant formulation is strongly recommended for chemical flooding because of its high efficacy and relatively low cost.

6-Aminocoumarin oxime-ether/sulfonamides as selective hCA IX and XII inhibitors: Synthesis, evaluation, and molecular dynamics studies.

Carbonic anhydrase isoforms IX and XII are overexpressed in hypoxic tumor cells regulating various physiological processes such as cell proliferation, invasion, and metastasis, resulting in the onset and spread of cancer. Selective inhibition of these enzymes is a promising strategy for anticancer therapy. Coumarin derivatives were identified as selective and potent inhibitors of these isoforms. This study reports 6-aminocoumarin sulfonamide and oxime ether derivatives linked through a chloroacetyl moiety tethered to piperazine and piperidone, respectively, showing selective inhibition against human carbonic anhydrase (hCA) IX and XII with Ki ranging from 0.51 to 1.18 µM and 0.89-4.43 µM. While the sulfonamide derivative 8a exhibited submicromolar inhibition against hCA IX and XII with Ki 0.89 and 0.51 µM, the oxime ether derivatives showed lower activity than the sulfonamides, with the compound 5n inhibiting hCA IX and hCA XII with a Ki of 1.055 and 0.70 µM, respectively. The above results demonstrate the potential of these derivatives as selective, potent inhibitors of carbonic anhydrase IX and XII and provide a foundation for further optimization and development as effective anticancer agents. Further, the binding mode of the synthesized derivatives in the active site were examined using molecular docking and dynamic simulation studies.

1-D MOF [Ag2(C10H10N3O3S)2(C4H8N)2]n: photocatalytic treatment, crystallographic evaluation, ADMET parameters, CT-DNA and anticancer activity

Newly synthesized dinuclear crystalline polymer, the silver complex of bidentate Sulfamethoxazole (Ag-SMX) in the presence of secondary ligand pyrrolidine has been characterized by elemental, spectral (1H-NMR spectra, FT-IR spectra, UV–Vis spectra.), powder XRD, and single-crystal X-ray diffraction (single-crystal) analysis. The synthesis molecular structure of the dinuclear [Ag2(C10H10N3O3S)2(C4H8N)2]n complex reveals a one-dimensional polymeric chain with seesaw geometry (τ4 = 0.71): two silvers interlink each other by argentophilic interaction with Ag1…Ag2 separation distance of 3.0047(6) Å. The Hirshfeld surfaces (HS) and 2D fingerprint plots were used to examine the interconnects in the crystal packing. Molecule properties including MEP, MPA, HOMO-LUMO energy, and global reactivity descriptor parameters were computed to understand the molecule’s stability. From ADMET parameters, human Intestinal Absorbance data revealed that the compound has the potential to be well absorbed, and also Ag-smx complex cannot cross the blood-brain barrier (BBB). The capacity of the silver complex to interact with CtDNA was investigated using absorption spectroscopy and viscosity tests. The interaction between CT-DNA reveals that the Ag-SMX complex exhibits the strongest binding affinity among all known sulfonamide derivatives and their metal complexes. The silver complex has higher inhibitory action than the free SMX ligand, according to data from a panel of gram (+ve) and gram (-ve) organisms’ minimum inhibitory concentrations. In vitro cytotoxicity investigation revealed that the IC50 value for Ag-SMX is 57.12 g/mL and for SMX is 100.90 g/mL against human lung cancer cell line (A549). This study revealed that, when compared to SMX free-ligand, Ag-SMX is the most effective in terms of cytotoxicity toward the human lung cancer cell line (A549 cell line). In under 120 min, the synthesized Ag-smx complex showed exceptional photo-degradation characteristics against methylene blue (MB) (10 ppm) in visible light radiation. Communicated by Ramaswamy H. Sarma

Theoretical Study on the Alkylimino-Substituted Sulfonamides with Potential Biological Activity.

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 pKa, 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 pKa values for each of the studied compounds. Interestingly, the use of Muckerman's approach for pKa determination exhibits that theoretical and experimental results are in very good agreement. Intramolecular hydrogen bond formation affects pKa. 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 P) 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.

Discovery of Anti‐Breast Cancer Thiophene Sulfonamide Derivatives: Design, Synthesis, Molecular Docking against EGFR, MM‐PBSA, MD Simulations, ADME/Tox, and in vitro Studies

AbstractWith aim of developing the crucial pharmacophoric properties of the reported EGFR inhibitors (EGFRIs), a series of thiophene compounds having ethyl 5‐methylthiophene‐3‐carboxylate core were designed. The designed compounds were subjected to molecular docking studies that indicated the potentialities of compounds AP−A8, A9, A13 and A15 to be EGFRIs. Then, the MD simulations studies confirmed the stability and the correct binding of compound AP−A15 – EGFR complex at both energetic and conformational levels. Furthermore, in silico ADMET prediction revealed that the majority of the proposed compounds had drug‐like characteristics and have minimal toxicity and unfavourable side effects. The designed compounds were synthesized and there in vitro anticancer activity against the cancer cell line (MCF‐7) was measured. Ethyl 5‐methyl‐4‐phenyl‐2‐(2‐(4‐(thiophen‐2‐ylsulfonyl)piperazin‐1‐yl)acetamido)thiophene‐3‐carboxylate (AP−A15) was found to be most potent compound with EC50 values 3.5 μM, which was very close to Tamoxifen and Brigatinib. Majority compounds showed good to moderate cytotoxic activities ranging from 3.5 μM to 35.9 μM.

Design, synthesis, and biological studies of novel sulfonamide derivatives as farnesoid X receptor agonists

Farnesoid X receptor (FXR) is considered as a promising target for the treatment of NASH. Although many non-steroidal FXR agonists have been reported, the structure types are quite scarce and mainly limited to the isoxazole scaffold derived from GW4064. Therefore, it is crucial to expand the structure types of FXR agonist to explore wider chemical space. In this study, the structure-based scaffold hopping strategy was performed by hybrid FXR agonist 1 and T0901317, which resulted in the discovery of sulfonamide FXR agonist 19. Molecular docking study reasonably explained the SAR in this series, and compound 19 fitted well with the binding pocket in a similar mode to the co-crystal ligand. In addition, compound 19 exhibited considerable selectivity against other nuclear receptors. In NASH model, compound 19 alleviated the typical histological features of fatty liver, including steatosis, lobular inflammation, ballooning, and fibrosis. Moreover, compound 19 exhibited acceptable safety profiles with no acute toxicity to major organ. These results suggested that the novel sulfonamide FXR agonist 19 might be a promising agent for the treatment of NASH.

In-silico screening based on molecular simulations of 3,4-disubstituted pyrrolidine sulfonamides as selective and competitive GlyT1 inhibitors

A systematic in-silico study based on molecular modeling techniques was conducted on thirty 3,4-disubstituted pyrrolidine sulfonamides derivatives to identify the drug candidate for treating schizophrenia and impairments associated with NMDA receptor hypofunction, through selective and competitive inhibition of GlyT1. QSAR analysis demonstrates that geometric and constitutional descriptors have a key function in human GlyT1 activity. The in-silico study concluded that the most active ligand labeled C19 was predicted to be a non-toxic inhibitor, with a desired ADME-Toxicity profile and a significant probability to penetrate the central nervous system (CNS). Molecular docking simulations confirmed that the C19 compound was docked to the active sites of drosophila melanogaster dopamine transporter (DAT) protein, creating a variety of chemical bonds towards TYR 124, ASP 475, GLU 480, ALA 479, and VAL 120 amino acids residues. The molecular dynamic (MD) technique combined with the MMGBSA approach confirmed that produced intermolecular interactions for the (DAT protein–C19 ligand) complex remain so stable during 100 ns of MD simulation time. Consequently, the C19 ligand is highly recommended for the treatment of schizophrenia and other disabilities linked to the hypofunction of glutaminergic NMDA receptors.

Inhibitive, Adsorption Studies on Carbon Steel Corrosion in Acidic Solutions by New Synthesized Benzene Sulfonamide Derivatives

Inhibitive, Adsorption Studies on Carbon Steel Corrosion in Acidic Solutions by New Synthesized Benzene Sulfonamide Derivatives

Intercalation of sulfonamides in montmorillonite by molecular dynamics and DFT calculations for bioavailability control

The intensive use of antibiotics and especially sulfonamides in the livestock industry is getting an alarming level. The presence of these drugs in wastewaters, rivers and underground waters is increasing considerably in developing countries. The molecular interactions of these drugs with the surfaces of clay minerals can be interesting for evaluating their mobility in soils and for preparing composite complexes for optimal use. In this work, the intercalation of antibiotics derivatives of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfachloropyridazine and sulfacetamide, into the interlayer space of montmorillonite (MNT) is studied at molecular and 3-D periodical crystal structure level by using computational modeling, molecular dynamics and calculations based Density Functional Theory (DFT). Most of these intercalations are energetically favourable, where the role of water molecules is critical. In general, the bioavailability of these compounds by intercalation in MNT is bigger than from the crystalline powder. Spectroscopic properties of these systems showed interesting frequency shifts in the bands of the IR spectrum produced during the intercalation in the confined space of MNT. These results predict that the IR spectroscopy as an interesting analytical technique for monitoring the intercalation of drugs in clay minerals.

Investigation of the Anti-Plasmodial Properties of N-2-Oxo Pyrrolidine Pentanamide-Based Sulfonamides: Experimental and Theoretical Approach

The study aimed to investigate novel pyrrolidine-pentanamide derivatives of sulfonamides as potential anti-malaria agents through a comprehensive approach involving experimental, theoretical, and in silico evaluations. The compounds were synthesized using standard methods and characterized using NMR, FT-IR, and HRMS techniques. The molecular properties of the compounds were investigated using density functional theory (DFT) at the B3LYP-D3 meta-functional/GenECP theoretical level. The calculated vibrational frequencies of the compounds showed good agreement with experimental results, validating the accuracy of the theoretical approach in capturing the behavior of different functional groups. Molecular docking simulations were performed to assess the binding affinity of the compounds to the amino acid residues binding sites of two target proteins: farnesyl pyrophosphate synthase (PDB ID: 1RQJ) and Plasmodium falciparum 80S ribosome (PDB ID: 3J7A). Substantially, the results of the docking simulations demonstrated that three compounds, namely 3-Methyl-2-(4-methylphenylsulfonamido)-N-(2-oxo-2-(pyrrolidin-1-yl)ethyl)pentanamide (MMOPEP), 3-Methyl-N-(2-oxo-2-(pyrrolidin-1-yl)ethyl)-2-(phenylsulfonamido)pentanamide (MOPEPP), and 3-Methyl-2-(4-nitrophenylsulfonamido)-N-(2-oxo-2-(pyrrolidin-1-yl)ethyl)pentanamide (MNOPEP), exhibited tight binding to the target proteins. These compounds showed favorable docking scores compared to standard drugs, indicating their potential as anti-malaria agents. Additionally, the high electrophilicity index recorded for the three compounds further supports their suitability as anti-malaria agents. The results collectively suggest that the pyrrolidine-pentanamide derivatives of sulfonamides have promising interactions with the target proteins, indicating their potential effectiveness against malaria. This study provides valuable insights into the molecular properties and binding affinities of the synthesized compounds, contributing to the development of new anti-malaria therapies.

First discovery of sulfonamides derivatives with acetylcholinesterase inhibitory activity in fungus Pestalotiopsis sp. HNY36-1D

Three rare natural sulfonamide products, sargassulfamide A (1), together with two unreported sulfonamides pestasulfamides B (2) and A (3) were obtained from mangrove endophytic fungus Pestalotiopsis sp. HNY36-1D under the guidance of chemical and biological autoradiography. Their structures were determined by 1D and 2D NMR, HR-ESI-MS, as well as single crystal X-ray diffraction. It was noteworthy that sulfonamide derivatives were obtained from metabolites of fungi for the first time. In bioassay, compounds 1 and 3 showed moderate acetylcholinesterase (AChE) inhibitory activities with IC50 values 28.41 and 11.94 μM, respectively. The structure-activity relationships (SARs) analysis suggested that the existence of hydrogen atom on the N atom of sulfonamide derivatives and the closed loop of cyclic dipeptide were beneficial to the activity. The molecular docking studies indicated that 1 and 3 were near the center of the active pocket of AChE, while 2 was at the edge of the protein due to the large steric hindrance.

New sulfonamide derivatives based on 1,2,3-triazoles: synthesis, in vitro biological activities and in silico studies

Eight new hybrid constructs containing a series of sulfonamide and 1,2,3-triazole units were designed and synthesized. Anticancer, antioxidant and cholinesterase activities of these hybrid structures were investigated. In our design, the Cu(I)-catalyzed click reaction between N,4-dimethyl-N-(prop-2-yn-1-yl)benzenesulfonamide (6) and aryl azides 8a–h was used. Antioxidant activity values of 9f (IC50: 229.46 ± 0.001 μg/mL) and 9h (IC50: 254.32 ± 0.002 μg/mL) hybrid structures were higher than BHT (IC50: 286.04 ± 0.003 μg/mL) and lower than Ascorbic acid (IC50: 63.53 ± 0.001 μg/mL) and α-Tocopherol (IC50: 203.21 ± 0.002 μg/mL). We determined that the cytotoxic effects of hybrid constructs 9d (IC50: 3.81 ± 0.1084 µM) and 9g (IC50: 4.317 ± 0.0367 µM) against A549 and healthy cell line (HDF) are much better than standard cisplatin (IC50: 6.202 ± 0.0705 µM). It was determined that the AChE inhibitory activities of all synthesized compounds were much better than Galantamine used as a standard. In particular, 9c (IC50: 13.81 ± 0.0026 mM) had ten times better activity than the standard Galantamine (IC50: 136 ± 0.008 mM). The ADMET properties of the molecules have been thoroughly examined and met the criteria for drug-like substances. They also have a high oral absorption rate, as they can effectively cross the blood–brain barrier and are easily absorbed in the gastrointestinal tract. In vitro experiments were confirmed by in silico molecular docking studies. Communicated by Ramaswamy H. Sarma

Pharmacological Properties of Sulfonamide Derivatives, New Inhibitors of Carbonic Anhydrase.

Selective blocking of individual isoforms of carbonic anhydrase (CA) is now one of the main directions in the development of its inhibitors. The new 1,2,4-oxadiazole-containing sulfonamides B12 and B13 predominantly block CA II and CA IX. The study of acute toxicity of B12 and B13 showed their safety. Substance B13 caused a relatively short-term, but rapid (within 30 min) decrease in the intraocular pressure in rabbits, which indicates the promise of its use for the emergency decrease in the intraocular pressure in medical practice. Analysis of the effects of sulfonamides on the functions of CNS showed that compound B12 probably exhibit tranquilizing activity; B13 is promising for the creation of drugs that have an antidepressant effect and at the same time increase the mental and physical performance.