Article
Chemistry, Medicinal
Ozlem Akgul, Srishti Singh, Jacob T. Andring, Robert McKenna, Silvia Selleri, Fabrizio Carta, Andrea Angeli, Claudiu T. Supuran
Summary: A series of taurine substituted sulfonamide derivatives with ureido moiety at the tail section were synthesized as selective inhibitors of tumor associated human Carbonic Anhydrase (CA) IX and XII. These derivatives showed a strong dependence on the presence of ureido moiety and demonstrated highly stabilized ligand-protein complex with specific amino acid residues in both hCA II and hCA IX-mimic.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Daniela Pagnozzi, Nicolino Pala, Grazia Biosa, Roberto Dallocchio, Alessandro Dessi, Pankaj Kumar Singh, Dominga Rogolino, Anna Di Fiore, Giuseppina De Simone, Claudiu T. Supuran, Mario Sechi
Summary: The letter describes the application of experimental and computational techniques to study the interactions between human carbonic anhydrases and sulfonamide inhibitors. A series of affinity-labeled carbonic anhydrase inhibitors containing sulfonamido photoprobes was designed and synthesized, and a photoaffinity labeling method followed by mass spectrometry analysis was applied to elucidate the inhibitor binding site. Comparisons with X-ray crystallography and molecular dynamics simulation data were made to fully understand the protein/inhibitor complex stabilization.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Anil Kumar Marapaka, Alessio Nocentini, Molly S. Youse, Weiwei An, Katrina J. Holly, Chittaranjan Das, Ravi Yadav, Mohamed N. Seleem, Claudiu T. Supuran, Daniel P. Flaherty
Summary: Drug-resistant Neisseria gonorrhoeae poses a serious threat to public health. The research team solved the structure of carbonic anhydrase inhibitors bound to the essential alpha-carbonic anhydrase isoform from N. gonorrhoeae, revealing differences compared to the human enzyme.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Andrea Angeli, Marta Ferraroni, Alessandro Bonardi, Claudiu T. Supuran, Alessio Nocentini
Summary: Carbonic anhydrases (CAs) are important zinc metalloenzymes that catalyze the hydration of carbon dioxide. They play crucial roles in various biological processes and can be targeted for the treatment of diseases like glaucoma, obesity, and cancer. In this study, we report the co-crystallization of a N-nitro sulphonamide derivative with human CA II, revealing the binding site and mode of inhibition. This knowledge could aid in the development of more potent and selective CA inhibitors.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Atteeque Ahmed, Aftab Ahmed, Pervaiz Ali Channar, Syeda Abida Ejaz, Aisha A. Alsfouk, Aamer Saeed, Rabail Ujan, Qamar Abbas, Tuncer Hokelek, Michael Bolte
Summary: Carbonic anhydrases (CAs) are widely expressed metalloenzymes that play a crucial role in various physiological and pathological processes. An alkyl substituted acyl thiourea compound was synthesized and characterized using NMR spectroscopy and single crystal X-ray diffraction. The synthesized compound showed hydrogen bonding and H···H interactions, and demonstrated inhibition of carbonic anhydrase activity. Quantum mechanical descriptors, molecular docking, and ADMET analysis were performed to analyze the compound's properties and potential as a drug inhibitor of carbonic anhydrase.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Francesca Mancuso, Anna Di Fiore, Laura De Luca, Andrea Angeli, Giuseppina De Simone, Claudiu T. Supuran, Rosaria Gitto
Summary: To address the challenge of isoform selectivity, the entrance of the cavity for certain druggable human Carbonic Anhydrases (hCAs) was explored. Using X-ray crystallographic studies, a series of 4-(4(hetero)aroylpiperazine-1-carbonyl)benzene-1-sulfonamides was developed based on complex with hCA VII. Through docking simulations, the capability of newer benzenesulfonamides to fit the hCA VII catalytic cavity was evaluated. Subsequently, a series of thirteen benzenesulfonamides was synthesized and tested, with the 4-(4-(furan-2-carbonyl)piperazine-1-carbonyl)benzenesulfonamide showing significant affinity towards hCA VII and good selectivity over hCA I when compared to Topiramate (TPM).
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Priti Singh, Abhishek Choli, Baijayantimala Swain, Andrea Angeli, Santosh K. Sahoo, Venkata M. Yaddanapudi, Claudiu T. Supuran, Mohammed Arifuddin
Summary: Indole is a widely used structure in drug design and development studies due to its broad bioactivities. Novel urea derivatives of indole with sulfonamide at position-3 were synthesized and found to specifically inhibit human-origin carbonic anhydrase II, with derivative 6l being the most active.
ARCHIV DER PHARMAZIE
(2022)
Article
Chemistry, Medicinal
Arzu Gumus, Murat Bozdag, Andrea Angeli, Thomas S. Peat, Fabrizio Carta, Claudiu T. Supuran, Silvia Selleri
Summary: In this study, a small series of compounds with inhibitory properties for human Carbonic Anhydrase enzymes were reported for the first time. Some of these compounds showed good selectivity for specific CAs, and one compound exhibited nearly matching K-I values for both hCA II and IX. X-ray crystal experiments were used to explore the binding mode of this compound within the CA IX mimic isoform.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Alessandro Bonardi, Silvia Bua, Jacob Combs, Carrie Lomelino, Jacob Andring, Sameh Mohamed Osman, Alessandra Toti, Lorenzo Di Cesare Mannelli, Paola Gratteri, Carla Ghelardini, Robert McKenna, Alessio Nocentini, Claudiu T. Supuran
Summary: Human carbonic anhydrase isoforms IX and XII have been confirmed as anticancer targets, with three-tails approach showing higher selectivity against tumor-associated isoforms and demonstrating anti-proliferative effects in various cancer cell lines. X-ray crystallography studies have been conducted to investigate the binding mode of these inhibitors, providing valuable insights for potential cancer treatments.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Biology
Emma Langella, Davide Esposito, Simona Maria Monti, Claudiu T. Supuran, Giuseppina De Simone, Vincenzo Alterio
Summary: Carbonic anhydrases are enzymes involved in an important physiological reaction of converting CO2 to bicarbonate ion. They play crucial roles in various physiological and pathological processes in humans, making them potential targets for therapeutic interventions. This study investigates a class of carbonic anhydrase inhibitors, providing insights into their mechanism of action and potential for drug design.
Article
Chemistry, Medicinal
Andrea Angeli, Marta Ferraroni, Antonella Capperucci, Damiano Tanini, Gabriele Costantino, Claudiu T. Supuran
Summary: This study presents the activity of selenocarbamates as novel carbonic anhydrase (CA) inhibitors. Through CA-mediated hydrolysis, selenocarbamates release selenolates that effectively inhibit CA by binding to zinc. Different human CA isoforms were evaluated against a series of selenocarbamates with high molecular diversity and complexity. X-ray studies provided insights into the binding mode of this novel class of CA inhibitors.
Article
Biochemistry & Molecular Biology
Ashraf K. El-Damasy, Hyun Ji Kim, Alessio Nocentini, Seon Hee Seo, Wagdy M. Eldehna, Eun-Kyoung Bang, Claudiu T. Supuran, Gyochang Keum
Summary: A series of 6-ureido/amidocoumarins were designed and synthesised to develop potent and isoform-selective carbonic anhydrase inhibitors. The target coumarins effectively inhibited tumour-related isoforms hCA IX and hCA XII, while not inhibiting cytosolic off-target isoforms hCA I and II. The most promising compound, 3,5-bis-trifluoromethylphenyl ureidocoumarin 5i, showed the best anticancer activity.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Davide Sbravati, Alessandro Bonardi, Silvia Bua, Andrea Angeli, Marta Ferraroni, Alessio Nocentini, Alessandro Casnati, Paola Gratteri, Francesco Sansone, Claudiu T. Supuran
Summary: Carbonic anhydrases (CAs) are still considered as an important pharmaceutical target due to the need for selective inhibitors and their involvement in various diseases. This study successfully explored the preparation of new CA ligands by combining calixarenes with benzensulfonamide units, showing promising inhibition towards different CA isoforms. The results suggest the possibility of designing multifunctional inhibitors for this widely spread class of enzymes in the future.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Medicinal
Janis Leitans, Andris Kazaks, Janis Bogans, Claudiu T. Supuran, Inara Akopjana, Jekaterina Ivanova, Raivis Zalubovskis, Kaspars Tars
Summary: This study investigates the binding mechanisms between saccharin derivatives and human carbonic anhydrase IX (hCA IX), revealing their unique binding modes and providing insights into the interactions crucial for inhibitor efficacy and selectivity. The findings enhance our understanding of hCA inhibitor binding and inform the rational design of potent agents.
Article
Biochemistry & Molecular Biology
Lamya H. Al-Wahaibi, Bahaa G. M. Youssif, Ehab S. Taher, Ahmed H. Abdelazeem, Antar A. Abdelhamid, Adel A. Marzouk
Summary: A novel series of tri-aryl imidazole derivatives carrying benzene sulfonamide moiety were designed for their selective inhibitory activity against hCA IX and XII. Among them, six compounds showed potent and selective CA IX inhibition, with 5g and 5b demonstrating higher antiproliferative activity compared to other tested compounds. Docking studies of these two compounds revealed their favorable binding interactions with CA-IX, similar to that of ligand 9FK. Molecular modeling simulations supported the biological evaluation results.
Article
Biochemistry & Molecular Biology
Morteza Abdoli, Alessandro Bonardi, Claudiu T. Supuran, Raivis Zalubovskis
Summary: A one-pot two-step protocol was developed for the synthesis of novel 4-cyanamidobenzenesulfonamides, which showed effective inhibition towards both human and bacterial carbonic anhydrase enzymes.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Khulood H. Oudah, Walaa R. Mahmoud, Fadi M. Awadallah, Azza T. Taher, Safinaz E-S Abbas, Heba Abdelrasheed Allam, Daniela Vullo, Claudiu T. Supuran
Summary: This study reports the design and synthesis of a series of benzoylthioureido derivatives and their screening for carbonic anhydrase inhibitory activity. Some compounds exhibited potent selectivity and inhibitory activity against different CA isoforms. Additionally, molecular docking and ADME prediction studies were conducted to explore the interaction of these compounds with CA isoforms and predict their pharmacokinetics and physicochemical properties.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Heba T. Abdel-Mohsen, Ahmed M. El Kerdawy, Andrea Petreni, Claudiu T. Supuran
Summary: Novel benzenesulfonamide derivatives were synthesized as carbonic anhydrase inhibitors, demonstrating potent inhibitory activity against multiple CA isoforms at the nanomolar range. The compounds displayed selectivity towards specific isoforms and adopted similar binding modes through molecular docking simulations.
ARCHIV DER PHARMAZIE
(2023)
Article
Biochemistry & Molecular Biology
Afaf El-Malah, Ehab S. Taher, Andrea Angeli, Samar S. Elbaramawi, Zeinab Mahmoud, Nour Moustafa, Claudiu T. Supuran, Tarek S. Ibrahim
Summary: A series of novel quinoline derivatives with sulfonamide as zinc-binding group (ZBG) were synthesized as carbonic anhydrase (CA) inhibitors. The compounds exhibited efficient inhibition against tumor-associated CA isoforms IX and XII, with one particular hybrid 10b demonstrating significant activity against MCF-7 cancer cells under normal and hypoxic conditions. The compounds also induced apoptosis in MCF-7 and MDA-MB-231 cells and altered the Bax/Bcl expression ratio. Docking studies supported the biological findings, indicating the effectiveness of the regioisomeric tactic for the quinoline-based sulfonamide molecules in inhibiting tumor-relevant hCAs IX/XII.
BIOORGANIC CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Aiva Plotniece, Arkadij Sobolev, Claudiu T. Supuran, Fabrizio Carta, Fredrik Bjoerkling, Henrik Franzyk, Jari Yli-Kauhaluoma, Koen Augustyns, Paul Cos, Linda De Vooght, Matthias Govaerts, Juliana Aizawa, Paeivi Tammela, Raivis Zalubovskis
Summary: Natural products and analogues are valuable sources for the discovery of antibacterial drugs. The identification of bacterial metalloenzymes and the synthesis of selective inhibitors are interesting for the development of antibacterial agents due to increasing drug resistance. Peptide nucleic acids represent a novel strategy for targeting pathogens through antisense inhibition and development of antisense peptide nucleic acids. The review also discusses alternative therapeutic options and optimized in vitro and in vivo models for studying biofilm-related infections along with an overview of drug delivery nanosystems.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ashraf K. El-Damasy, Hyun Ji Kim, Alessio Nocentini, Seon Hee Seo, Wagdy M. Eldehna, Eun-Kyoung Bang, Claudiu T. Supuran, Gyochang Keum
Summary: A series of 6-ureido/amidocoumarins were designed and synthesised to develop potent and isoform-selective carbonic anhydrase inhibitors. The target coumarins effectively inhibited tumour-related isoforms hCA IX and hCA XII, while not inhibiting cytosolic off-target isoforms hCA I and II. The most promising compound, 3,5-bis-trifluoromethylphenyl ureidocoumarin 5i, showed the best anticancer activity.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Thor Eysteinsson, Andrea Garcia-Llorca, Arnar Oessur Hardarson, Daniela Vullo, Fabrizio Carta, Claudiu T. Supuran
Summary: Previous research has shown that carbonic anhydrase inhibitors (CAIs) can induce vasodilation in retinal arteriolar segments, but it is unclear which isoforms or mechanisms are responsible for this effect. In this study, four new CAIs that do not enter cell membranes but have high affinity for cytosolic and membrane-bound isoforms of CA were tested. None of these CAIs had a significant effect on arteriolar wall tension, while a membrane permeant CAI called benzolamide fully dilated all segments tested. This suggests that CAIs act as vasodilators through cellular mechanisms located in the cytoplasm of vascular cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Susanna Haapanen, Andrea Angeli, Martti Tolvanen, Reza Zolfaghari Emameh, Claudiu T. T. Supuran, Seppo Parkkila
Summary: This study reports the sequence enhancement, production, catalytic activity, and inhibition results of the beta-class carbonic anhydrase SmaBCA from intestinal parasite Schistosoma mansoni. The recombinant SmaBCA showed significant catalytic activity on CO2 hydration in vitro. Several sulphonamide inhibitors, including clinically used ones, exhibited submicromolar or nanomolar inhibitory effects on SmaBCA. The results suggest SmaBCA as a novel target for drug development against schistosomiasis.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Waleed A. A. Badawi, Mahmoud Rashed, Alessio Nocentini, Alessandro Bonardi, Mohammad M. M. Abd-Alhaseeb, Sara T. T. Al-Rashood, Giri Babu Veerakanellore, Taghreed A. A. Majrashi, Eslam B. B. Elkaeed, Bahaa Elgendy, Paola Gratteri, Claudiu T. T. Supuran, Wagdy M. M. Eldehna, Mohamed Elagawany
Summary: In this study, new pyridazine-based sulphonamides were developed as potential multi-target anti-inflammatory drugs, which can inhibit the CA, COX-2, and 5-LOX enzymes simultaneously, avoiding the drawbacks of using NSAIDs alone.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Shaimaa M. Aboukhatwa, Peter A. Sidhom, Andrea Angeli, Claudiu T. Supuran, Haytham O. Tawfik
Summary: A series of 15 chalcone-sulfonamide hybrids were designed with a less is more philosophy, expecting synergistic anticancer activity. These compounds showed potent inhibitors of cancer cell growth, particularly against colorectal carcinoma cells. They exhibited low to moderate potency as direct inhibitors of carbonic anhydrase catalytic activity, with compound 4d being the most potent. Compound 4j showed selectivity to carbonic anhydrase IX over other isoforms. Both compounds targeted carbonic anhydrase activity and exhibited cytotoxicity in cancer cells. This study presents 4d and 4j as potential candidates to be further developed as anticancer therapeutics.
Article
Biology
Emma Langella, Davide Esposito, Simona Maria Monti, Claudiu T. Supuran, Giuseppina De Simone, Vincenzo Alterio
Summary: Carbonic anhydrases are enzymes involved in an important physiological reaction of converting CO2 to bicarbonate ion. They play crucial roles in various physiological and pathological processes in humans, making them potential targets for therapeutic interventions. This study investigates a class of carbonic anhydrase inhibitors, providing insights into their mechanism of action and potential for drug design.
Article
Chemistry, Medicinal
German Benito, Ilaria D'Agostino, Simone Carradori, Marialuigia Fantacuzzi, Mariangela Agamennone, Valentina Puca, Rossella Grande, Clemente Capasso, Fabrizio Carta, Claudiu T. Supuran
Summary: In this study, dual-acting antibacterial agents containing Erlotinib were synthesized and evaluated. Some of the compounds showed strong inhibitory activity against Helicobacter pylori carbonic anhydrase and good antibacterial activity against H. pylori. Computational studies provided insights into the binding mode of these compounds.
FUTURE MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Gioele Renzi, Fabrizio Carta, Claudiu T. Supuran
Summary: Integration of viral RNA into host genomes is a crucial step in retroviral replication, catalyzed by the conserved virus-encoded enzyme Integrase (IN). The authors discuss the discoveries and advances in developing targeted inhibitors for HIV-IN as therapeutic applications. The accumulated knowledge serves as a valuable resource for designing effective antiretroviral drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Xiaojing Huang, Daniel Winter, Dominic. J. J. Glover, Claudiu. T. T. Supuran, William. A. A. Donald
Summary: Carbonic anhydrases (CAs) are metalloenzymes that play important roles in cellular processes and have been implicated in various diseases. Phosphorylation, a common post-translational modification of CAs, can significantly impact their catalytic activity and drug-binding capabilities. This study highlights the potential regulatory role of phosphorylation in CA activity and its effect on small molecule drug binding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)