Novel Schiff Base Sulfonate Derivatives as Carbonic Anhydrase and Acetylcholinesterase Inhibitors: Synthesis, Biological Activity, and Molecular Docking Insights DOI Open Access
Ümit Yaşar, Yeliz Demir, İlyas Gönül

et al.

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

ABSTRACT Sulfonate derivatives are an essential class of compounds with diverse pharmacological applications. This study presents the synthesis and detailed characterization six novel Schiff base sulfonate ( L 1 –L 6 ) through spectroscopic techniques (FT‐IR NMR). Their inhibitory potential was evaluated against human carbonic anhydrase isoenzymes h CA I II) acetylcholinesterase (AChE), which crucial therapeutic targets for diseases such as glaucoma, epilepsy, Alzheimer's disease. The K values concerning AChE, I, II enzymes were in ranges 106.10 ± 14.73 to 422.80 17.64 nM (THA: 159.61 8.41 nM), 116.90 24.40 268.00 35.84 (AAZ: 439.17 9.30 177.00 35.03 435.20 75.98 98.28 1.69 respectively. Molecular docking analyses revealed key interactions within active sites enzymes, including hydrogen bonding critical residues π–π stacking interactions. Notably, 3 demonstrated superior inhibition : nM) AChE positioning it a promising lead compound. comprehensive investigation contributes development isoform‐specific inhibitors use provides valuable insights into their binding mechanisms. findings underscore sulfonates scaffolds drug discovery neurodegenerative metabolic disorders.

Language: Английский

Novel 3-Sulfonamide Dual-Tail Pyrrol-2-one Bridged Molecules as Potent Human Carbonic Anhydrase Isoform Inhibitors: Design, Synthesis, Molecular Modeling Investigation, and Anticancer Activity in MeWo, SK-BR-3, and MG-63 Cell Lines DOI Creative Commons
Cristina M. Al Matarneh, N Simiónescu, Alina Nicolescu

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Novel 3-sulfonamide pyrrol-2-one derivatives containing two sulfonamide groups were synthesized via a one-pot, three-component method using trifluoroacetic acid as catalyst. Structural confirmation was achieved spectroscopic techniques. The compounds tested against four selected human carbonic anhydrase isoforms (hCA I, hCA II, IX, and XII). Most showed significant selectivity for with 4h, 4i, 4n, 4k, 4j demonstrating enhanced activity due to methoxy hydroxy group patterns. Compound 4o exhibited strong dual II while 4l the most effective inhibitor of XII. Additionally, 4e preference XII inhibition. Biological evaluation on MeWo, SK-BR-3, MG-63 cancer cells that compound cytotoxic MeWo without significantly affecting normal fibroblasts' viability. Compounds 4e, 4l, shown affect tumor cell viability in combination doxorubicin additional testing cells.

Language: Английский

Citations

0
On QSPR analysis of glaucoma drugs using machine learning with XGBoost and regression models DOI

Lina Huang,

Khawlah Alhulwah,

Muhammad Farhan Hanif

et al.

Computers in Biology and Medicine, Journal Year: 2025, Volume and Issue: 187, P. 109731 - 109731

Published: Jan. 28, 2025

Language: Английский

Citations

0
Structural Studies of the Dopamine D4 Receptor Antagonist Sonepiprazole as an Inhibitor of Human Carbonic Anhydrases DOI
Andrea Angeli, Marta Ferraroni, Clemente Capasso

et al.

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: 16(3), P. 483 - 486

Published: Feb. 10, 2025

In this study, we provide the first evidence that sonepiprazole, a dopamine D4 receptor antagonist, acts as potent inhibitor of human carbonic anhydrases (hCAs). Sonepiprazole exhibited significant inhibitory activity across panel catalytically active hCAs, with exception hCA IV, and III. The most inhibition was observed against brain-associated isoform VII, KI 2.9 nM. Insights from X-ray crystallographic structures complexes I, II, XII revealed sulfonamide group sonepiprazole coordinates zinc ion in site, typical interaction for class inhibitors. Despite presence isoform-specific residues at rim site pocket, these variations seem not to significantly impact compound overall potency. These findings highlight dual functionality both antagonist anhydrase inhibitor.

Language: Английский

Citations

0
Synthesis, molecular docking study, molecular dynamics simulation and ADMET prediction of new Sulfa drugs having CA II Inhibitory effect and antidiabetic activity. DOI
Sali̇ha Alyar, Ümmühan Özdemir Özmen, Şevki Adem

et al.

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 142015 - 142015

Published: March 1, 2025

Language: Английский

Citations

0
Dual inhibition of carbonic anhydrases VA and VII by silychristin and isosilybin A from Silybum marianum: A potential antiobesity strategy DOI Creative Commons
Emanuele Liborio Citriniti, Roberta Rocca, Giosuè Costa

et al.

Archiv der Pharmazie, Journal Year: 2025, Volume and Issue: 358(3)

Published: March 1, 2025

Abstract Obesity is a global health crisis linked to chronic diseases like cardiovascular disease and type 2 diabetes. Its prevalence, even in low‐income countries, highlights the failure of traditional interventions. Safer pharmacological treatments are urgently needed, as many existing antiobesity drugs have been withdrawn due severe side effects, leaving critical therapeutic gap. A promising target this context human carbonic anhydrase V ( h CA V), mitochondrial enzyme that plays key role glucose homeostasis. Inhibiting has shown reduce lipogenesis improve metabolic conditions. Natural plant extracts, such silymarin from milk thistle, demonstrated potential managing obesity‐related syndromes by lowering triglycerides, reducing cholesterol levels, improving liver function. Our computational studies identified active compounds effectively inhibit V, shedding light on mechanism for its effects. Building these findings, our research further reveals also VII VII), enhancing their potential. This dual inhibitory action addresses both dysregulation oxidative stress. Notably, antioxidant properties provide additional protection against complications mitigating stress, contributor development syndrome.

Language: Английский

Citations

0
A Journey Around Boronic Acids: Sulfonyl Hydrazone‐Containing Derivatives as Carbonic Anhydrase Inhibitors DOI

Deniz Akin Anakok,

Andrea Angeli, Ilaria D’Agostino

et al.

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(4)

Published: April 1, 2025

ABSTRACT Recently, a rising interest in boronic acids and their derivatives was recorded the Medicinal Chemistry field due to high versatility broad applicability as bioactive compounds several diseases, including cancer microbial infections. The ability of acid moieties bind zinc ions first hypothesized by inhibitory activity bortezomib, boron‐containing protease inhibitor, on different isoforms Carbonic Anhydrase (CA, EC: 4.2.1.1) enzyme family then assessed through X‐ray crystallographic studies benzoxaboroles complex with hCA II. These findings, along overexpression IX XII hypoxic and, particular, breast cancer, drove us explore chemical space around phenylboronic generating focused library 16 (1–4a–d) decorated alkyl sulfonyl hydrazones. were subjected stopped flow‐based inhibition assays panel hCAs, tumor‐associated isoforms, revealing low micromolar constants ( K I s) some cases. However, antiproliferative conducted human triple‐negative cell line showed lack at tested concentrations.

Language: Английский

Citations

0
Exploring the Polypharmacological Potential of PCI-27483: A Selective Inhibitor of Carbonic Anhydrases IX and XII DOI
Ilaria D’Agostino, Alessandro Bonardi, Marta Ferraroni

et al.

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(11), P. 2042 - 2045

Published: Oct. 21, 2024

PCI-27483, originally developed as a potent and selective inhibitor of the serine protease Factor VIIa (FVIIa) in complex with tissue factor (TF), has demonstrated significant promise cancer therapy. In addition to its primary mechanism action, presence sulfonamide moiety PCI-27483 structure suggests further activities through inhibition carbonic anhydrases (CAs), particularly tumor-associated human (h)CA isoforms hCA IX XII. This study investigates inhibitory activity against complete panel active hCAs, highlighting polypharmacological potential treatment. X-ray crystallography molecular docking studies elucidated structural features underlying toward XII, offering insights into dual-targeting pathway.

Language: Английский

Citations

3
Novel 2,4-Dichloro-5-sulfamoylbenzoic Acid Oxime Esters: First Studies as Potential Human Carbonic Anhydrase Inhibitors DOI
Jaydeo T. Kilbile, Suryakant B. Sapkal, Gioele Renzi

et al.

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(6), P. 972 - 978

Published: May 23, 2024

In this study, a focused library of oxime ester derivatives 2,4-dichloro-5-sulfamoylbenzoic acid (lasamide) containing Schiff bases was synthesized and tested in vitro for their ability to inhibit the cytosolic human carbonic anhydrases (hCAs) I II, as well transmembrane tumor-associated IX XII isoforms. As result, we obtained first line knowledge on lasamide potentially useful development CA inhibitors (CAIs). particular, our attention derivative 11, which selective toward hCAs over isoenzymes. An silico study conducted assess binding mode 11 within XII. Also, antiproliferative assays highlighted promising derivatives. The data are currently use better-performing compounds

Language: Английский

Citations

2
Diiodine–Triethylsilane System: Formation of N-Alkylsulfonamides from Benzylic Alcohols and Sulfonamides DOI
Jiang Jin, Zhuo Wang, Lili Xiao

et al.

Synlett, Journal Year: 2024, Volume and Issue: unknown

Published: May 14, 2024

Abstract An operationally simple method has been developed for the synthesis of N-alkylsulfonamides from benzylic alcohols and sulfonamides in presence molecular iodine triethylsilane. Various were evaluated, iodides generated situ shown to be key intermediates.

Language: Английский

Citations

0
Thia‐ and Seleno‐Michael Reactions for the Synthesis of Carbonic Anhydrases Inhibitors DOI Creative Commons
Andrea Angeli,

Alessio Occhini,

Gioele Renzi

et al.

ChemMedChem, Journal Year: 2024, Volume and Issue: 19(20)

Published: June 21, 2024

Novel chalcogen-containing amides and esters bearing the benzenesulfonamide moiety have been synthesised upon nucleophilic conjugate addition of thiols selenols to suitable electron-deficient alkenes. The activity compounds as Carbonic Anhydrases inhibitors has investigated in vitro inhibition mechanism elucidated by X-rays studies.

Language: Английский

Citations

0