Novel beta-lactam substituted benzenesulfonamides: in vitro enzyme inhibition, cytotoxic activity and in silico interactions

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер 42(12), С. 6359 - 6377

Опубликована: Авг. 4, 2023

In this study, a library of twelve beta-lactam-substituted benzenesulfonamides (

Язык: Английский

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New naphthoquinone thiazole hybrids as carbonic anhydrase and cholinesterase inhibitors: Synthesis, crystal structure, molecular docking, and acid dissociation constant

Journal of Molecular Structure, Год журнала: 2023, Номер 1301, С. 137365 - 137365

Опубликована: Дек. 19, 2023

Язык: Английский

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Novel asymmetric biscarbothioamides as Alzheimer's disease associated cholinesterase inhibitors: synthesis, biological activity, and molecular docking studies

New Journal of Chemistry, Год журнала: 2024, Номер 48(24), С. 10979 - 10989

Опубликована: Янв. 1, 2024

Investigating innovative frameworks for addressing Alzheimer's disease is a challenging goal. In this specific scenario, selection of asymmetric biscarbothioamide derivatives (3a–l) with different substitutions has been carefully formulated and successfully synthesized.

Язык: Английский

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Protective effects of esculetin against doxorubicin‐induced toxicity correlated with oxidative stress in rat liver: In vivo and in silico studies

Journal of Biochemical and Molecular Toxicology, Год журнала: 2024, Номер 38(4)

Опубликована: Апрель 1, 2024

Abstract Doxorubicin (DOX) is widely used in cancer treatment but the dose‐related toxicity of DOX on organs including liver limit its use. Therefore, there great interest combining with natural compounds antioxidant properties to reduce and increase drug efficacy. Esculetin a coumarin derivative biological encompassing anti‐inflammatory activities. In light these properties, this study was meticulously crafted investigate potential esculetin preventing doxorubicin (DOX)‐induced hepatotoxicity Sprague‐Dawley rats. The rats were divided into total six groups: control group, group (administered at cumulative dose 5 mg/kg intraperitoneally every other day for 2 weeks), E50 50 day), E100 100 day) combined groups (DOX + E100) which administered together DOX. treatments, both alone combination E50, manifested reduction catalase (CAT mRNA) levels comparison group. Notably, enzymatic activities superoxide dismutase (SOD), CAT, glutathione peroxidase (GPx) witnessed significant decreases treated Moreover, induced statistically elevation malondialdehyde (MDA) levels, coupled concurrent decrease (GSH) levels. Additionally, molecular docking studies conducted. However, further are needed confirm hepatoprotective precisely elucidate mechanisms action.

Язык: Английский

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Design, synthesis, characterization, antimicrobial activity, cytotoxicity, molecular docking, and in-silico ADMET analysis of the novel cefuroxime derivatives

European Journal of Medicinal Chemistry Reports, Год журнала: 2024, Номер 10, С. 100129 - 100129

Опубликована: Янв. 8, 2024

This research aims to design and synthesize novel derivatives of Cefuroxime evaluate their antibacterial effectiveness in comparison decrease resistance. Schotten Baumann's reaction synthesizes anhydride from acyl chlorides carboxylate anion. sodium was reacted with benzoyl chloride, 4-bromobenzoyl 4-nitrobenzoyl chloride make derivatives. The were characterized using spectral analysis. Antimicrobial activity, cytotoxicity, in-silico molecular docking nine different class (Penicillin Binding Proteins) PBPs, ADMET analysis assessed for the analogs. Three molecules, Cef-1, Cef-2, Cef-3, are synthesized In various organisms, outperformed antimicrobial activity. many Cef-1 has highest zone inhibition. Cef-3 inhibit Klebsiella pneumoniae better than Cef-2 Cefuroxime. greatest Cef-2-induced inhibition Salmonella Typhimurium 29.33 ± 0.47 mm. Significant susceptibility test activity observed lower inhibitory concentration (12.5 μg/ml) compared across species. Compound cytotoxicity is low, according research. consensus scores show that all bind cefuroxime. According results study, strongest correlation PBP1a, PBP2a, PBP3, PBP4, PBP6, whereas a stronger association PBP1b, PBP2b, PBP2x, PBP5. Like greater affinity PBP2x. Docking indicated drugs bound Cefuroxime, indicating superior efficacy. studies showed oral bioavailability increased by increasing lipophilicity score 0.17 cefuroxime 0.11.

Язык: Английский

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Isolation, bioactivity and molecular docking of stilbene acetylcholinesterase inhibitors from Arundina graminifolia (D. Don) Hochr.

Journal of Molecular Structure, Год журнала: 2025, Номер unknown, С. 141745 - 141745

Опубликована: Фев. 1, 2025

Язык: Английский

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Phthalazine ring incorporated 3-methyl-2,6-diarylpiperidin-4-one based hybrids: Synthesis, Spectral characterization, DFT studies, Molecular docking, In silico ADME predictions and Antibacterial activity

Journal of Molecular Structure, Год журнала: 2025, Номер 1334, С. 141791 - 141791

Опубликована: Фев. 18, 2025

Язык: Английский

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New Acetamide-Sulfonamide-Containing Scaffolds: Antiurease Activity Screening, Structure-Activity Relationship, Kinetics Mechanism, Molecular Docking, and MD Simulation Studies

Molecules, Год журнала: 2023, Номер 28(14), С. 5389 - 5389

Опубликована: Июль 13, 2023

The development of novel scaffolds that can increase the effectiveness, safety, and convenience medication therapy using drug conjugates is a promising strategy. As result, are an active area research in medicinal chemistry. This demonstrates acetamide–sulfonamide scaffold preparation after conjugation ibuprofen flurbiprofen with sulfa drugs, these were then screened for urease inhibition. newly designed confirmed by spectroscopic techniques such as IR, 1HNMR, 13CNMR, elemental analysis. Ibuprofen conjugated sulfathiazole, sulfadiazine, sulfamethoxazole found to be potent demonstrated competitive mode inhibition, IC50 (µM) values 9.95 ± 0.14, 16.74 0.23, 13.39 0.11, respectively, inhibition 90.6, 84.1, 86.1% respectively. sulfanilamide, sulfamerazine, sulfacetamide, whereas sulfacetamide exhibited mixed Moreover, through molecular docking experiments, receptor-binding mechanisms inhibitors anticipated, stability analysis MD simulations showed compounds made stable complexes respective targets no conformational changes occurred during simulation. findings demonstrate approved therapeutic molecules may result classes pharmacological agents treatment various pathological conditions involving enzyme.

Язык: Английский

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Exploring the potential of propanamide-sulfonamide based drug conjugates as dual inhibitors of urease and cyclooxygenase-2: biological and their in silico studies

Frontiers in Chemistry, Год журнала: 2023, Номер 11

Опубликована: Авг. 3, 2023

Derivative synthesis has been a crucial method for altering the effects of already-approved medications, especially to lessen adverse and enhance results. Making use this multi-target approach, series naproxen-sulfa drug conjugates was designed synthesized. The newly were confirmed by spectroscopic techniques like IR, 1HNMR, 13CNMR, elemental analysis. screened anti-inflammatory, urease, cyclooxygenase-2 (COX-2) inhibition. Naproxen conjugated with sulfanilamide, sulfathiazole, sulfaguanidine found potent showed competitive mode urease inhibition, IC50 (µM) values 6.69 ± 0.11, 5.82 0.28, 5.06 0.29, respectively. When compared other conjugates, naproxen-sulfamethoxazole conjugation better anti-inflammatory action inhibiting induced edema 82.8%, which is comparable medication indomethacin (86.8% inhibition). Whereas it exhibited 75.4% inhibition COX-2 at 10 µM concentration reference (celecoxib, 77.1% Moreover, binding modes inhibitors receptor predicted through molecular docking studies their stability analysis MD simulations that these compounds made stable complexes respective targets there no conformational changes occurred during simulation. obtained results approved therapeutic molecules may lead development novel types pharmacological agents in treatment several pathological disorders where enzymes are involved.

Язык: Английский

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Exploring the Potential of New Benzamide-Acetamide Pharmacophore Containing Sulfonamide as Urease Inhibitors: Structure–Activity Relationship, Kinetics Mechanism, and In Silico Studies

ACS Omega, Год журнала: 2023, Номер 8(48), С. 46165 - 46181

Опубликована: Ноя. 22, 2023

The search for novel drug scaffolds that can improve effectiveness and safety through conjugates is a promising approach. Consequently, constitute dynamic field of study advancement within medicinal chemistry. This research demonstrates the conjugation diclofenac mefenamic acid with sulfa drugs their screening urease inhibition. These conjugates' structural confirmation was performed using elemental analysis spectroscopic methods, including IR, 1H NMR, 13C NMR. Diclofenac conjugated sulfanilamide (4), sulfacetamide (10), (12), sulfamethoxazole (17) found potent demonstrated inhibition competitively, IC50 (μM) values 3.59 ± 0.07, 5.49 0.34, 7.92 0.27, 8.35 0.26, respectively. sulfathiazole (6), sulfamerazine (8), sulfaguanidine (11), while sulfisoxazole (13), (14), sulfadiazine (15) exhibited mixed mode were 16.19 0.21, 9.50 0.28, 4.35 0.23, 15.86 0.25, 14.80 Furthermore, molecular docking studies employed to predict binding pose competitive inhibitors at active site. generated stable complexes protein observed dynamics (MD) simulations, where no conformational changes occurred throughout simulations. results highlight potential approved therapeutic molecule give rise new categories pharmacological agents similarity sulfonamides urea allows them compete site enzyme. Sulfonamides nonsteroidal anti-inflammatory (NSAIDs) interact hydrophobically enzyme, which may disturb its structure catalytic activity. Therefore, these be helpful in development treatment variety illnesses enzyme involved.

Язык: Английский

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