A potential DNA protector, enzyme inhibitor and in silico studies of daucosterol isolated from six Nepeta species

Process Biochemistry, Год журнала: 2024, Номер 143, С. 234 - 247

Опубликована: Май 6, 2024

Язык: Английский

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Design, Synthesis, and In Vitro and In Silico Biological Exploration of Novel Pyridine‐Embedded 1,3,4‐Oxadiazole Hybrids as Potential Antimicrobial Agents

Journal of Chemistry, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Antibiotic resistance represents a significant public health challenge in the current century. The β‐lactam antibiotics, together with carbapenems, are inactivated by zinc‐dependent bacterial enzymes called metallo‐β‐lactamases (MBLs). Presently there no clinically permitted MBL inhibitors, and to produce such drugs, it is indispensable comprehend their inhibitory action. We investigated an efficient synthesis of pyridine‐embedded 1,3,4‐oxadiazole hybrids (3a-c) antimicrobial activity against different microbial strains. compounds were characterized spectral techniques (viz., IR, NMR, mass). vitro antibacterial antifungal was also performed; displayed excellent activity. silico docking studies evaluated proteins New Delhi Metallo-Beta-lactamase-1 (NDM‐1) Mycobacterium tuberculosis enoyl reductase (INHA). All demonstrated binding affinity for docked proteins. Additionally, molecular dynamics disclosed (4a-c) .

Язык: Английский

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New acetamide-sulfonamide scaffolds with potential renal radiomodulatory effects: Insights into NF-κB pathway interactions

Bioorganic Chemistry, Год журнала: 2025, Номер unknown, С. 108439 - 108439

Опубликована: Апрель 1, 2025

Язык: Английский

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The roles of bacteria on urolithiasis progression and associated compounds

Biochemical Pharmacology, Год журнала: 2025, Номер unknown, С. 116958 - 116958

Опубликована: Апрель 1, 2025

Язык: Английский

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Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors

Frontiers in Chemistry, Год журнала: 2024, Номер 12

Опубликована: Март 13, 2024

Urease, a nickel-dependent enzyme found in various life forms, catalyzes urea breakdown, concluding nitrogen metabolism by generating ammonia and carbamate. This process causes rise pH, supports the survival of pathogens, can lead to infections such as gastric disorders like ulcers cancer humans. Helicobacter pylori employs urease for acidic environment stomach protein synthesis. To treat inhibit growth it is mandatory obstruct activity; therefore, derivatives 1-(3-nitropyridin-2-yl)piperazine were synthesized ( 5a-o ; 7a-k ). All these newly compounds investigated inhibition vitro assays. The results showed that 5b 7e are most active inhibitors, having IC 50 values 2.0 ± 0.73 2.24 1.63 µM, respectively. These lower than value standard thiourea, which was 23.2 11.0 µM. hemolysis potential 5b, 5c, 5i, 7e, 7h also determined; exhibited good biocompatibility human blood cells. Through silico analysis, shown both potent inhibitors develop favorable interactions with site urease, binding energies −8.0 ) −8.1 kcal/mol. energy thiourea −2.8 Moreover, have high gastrointestinal permeability predicted via computational analysis. On other hand, precursor compound 3 3.90 1.91 µM −6.1 kcal/mol, Consequently, serve important urease.

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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Computational methods in glaucoma research: Current status and future outlook

Molecular Aspects of Medicine, Год журнала: 2023, Номер 94, С. 101222 - 101222

Опубликована: Ноя. 3, 2023

Язык: Английский

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Novel coumarin-based acetohydrazide-1,2,3-triazole derivatives as urease enzyme inhibitors: synthesis, in vitro evaluation, and molecular dynamics simulation studies

Heliyon, Год журнала: 2024, Номер 11(1), С. e41321 - e41321

Опубликована: Дек. 18, 2024

Язык: Английский

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Acetylsalicylic acid-sulfa drugs conjugates as potential urease inhibitors and anti-inflammatory agents: bio-oriented drug synthesis, molecular docking, and dynamics simulation studies

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер 42(18), С. 9373 - 9387

Опубликована: Авг. 29, 2023

AbstractTo explore the new mode of action and reduce side effects, making conjugates existing drugs is becoming an attractive tool in realm medicinal chemistry. In this work, we exploited approach synthesized to assess their activities against enzymes involved different pathological conditions. Specifically, design involving acetylsalicylic acid sulfa drugs, validating newly crafted using techniques like IR, 1HNMR, 13CNMR, elemental analysis. These underwent assessment for ability inhibit cyclooxygenase-2 (COX-2), urease enzymes, anti-inflammatory potential. A competitive inhibition was observed conjugated with sulfanilamide, sulfacetamide, sulfadiazine IC50 2.49 ± 0.35 µM, 6.21 0.28 6.57 0.44 respectively. Remarkably, acid-sulfamethoxazole conjugate exhibited exceptional activity, effectively curtailing induced edema by 83.7%, a result akin reference drug indomethacin's performance (86.8%). Additionally, it demonstrated comparable COX-2 (75.8%) selective inhibitor celecoxib that 77.1% at 10 µM concentration. To deepen our understanding, employed molecular docking predict binding interactions inhibitors receptors. MD simulations were carried out, confirming stability inhibitor-target complexes throughout simulation period, devoid significant conformational changes. Collectively, research underscores potential coupling approved compounds usher novel categories pharmacological agents, holding promise addressing wide spectrum disorders enzymes.Communicated Ramaswamy H. SarmaKeywords: NSAIDssulfonamidesinflammationcyclooxygenase-2ureasemolecular Authors' contributionsSaghir Ahmad: Methodology, Formal analysis, Synthesis, Muhammad Abdul Qadir: Supervision, Research Design, Mahmood Ahmed: Review & editing, Writing - original draft, Imran: Review, Numan Yousaf: Docking, Asnuzilawati Asari: Hameed: Validation data, Muddassar: Docking Simulation.Disclosure statementThe authors declare no conflict interest.Ethical statementAll animal experimental methods conducted as per guidelines UK Animals (Scientific Procedures) Act 1986, Animal Ethical Committee The University Punjab, Lahore-Pakistan. albino mice either sex kept under standard conditions house, EEC Directive 1986 (86/609/EEC) use laboratory animals (NIH Publication No. 80-23; revised 1978).Additional informationFundingThe received specific funding work.

Язык: Английский

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Jack bean urease inhibition by different root fractions of Cleome gynandra L – Kinetic mechanism and computational molecular modelling

Industrial Crops and Products, Год журнала: 2024, Номер 222, С. 119514 - 119514

Опубликована: Авг. 31, 2024

Язык: Английский

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