Article
Chemistry, Multidisciplinary
Thitima Pewklang, Kantapat Chansaenpak, Siti Nursyahirah Bakar, Rung-Yi Lai, Chin Siang Kue, Anyanee Kamkaew
Summary: AZB-I-CAIX(2) was developed as a photosensitizer targeting CAIX, showing specific affinity and enhanced photocytotoxicity in CAIX-expressed cancer cells, which could reduce tumor size by preventing PDT-induced hypoxia through CAIX inhibition.
FRONTIERS IN CHEMISTRY
(2022)
Article
Medicine, General & Internal
Mohammed Al-Zubaidi, Pravin Viswambaram, Steve McCombie, Elizabeth Liow, Nat Lenzo, Tom Ferguson, Andrew D. Redfern, Richard Gauci, Dickon Hayne
Summary: Bladder cancer is a lethal disease with limited conventional imaging modalities for accurate staging. This study aims to investigate the use of (89)Zirconium-labelled girentuximab PET in the staging of bladder and urothelial carcinomas.
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
Biochemistry & Molecular Biology
Toni C. Denner, Niels Heise, Julian Zacharias, Oliver Kraft, Sophie Hoenke, Rene Csuk
Summary: Acetylated triterpenoids were transformed into succinyl-spacered acetazolamide conjugates and tested for their inhibitory actvity on carbonic anhydrase II and cytotoxicity on human tumor cell lines and non-malignant fibroblasts. The conjugates derived from betulin and glycyrrhetinic acid showed the strongest inhibition, while those derived from ursolic or oleanolic acid were weaker inhibitors but had lower cytotoxicity. A betulin-derived conjugate displayed a Ki value of 0.129 μM and an EC50 value of 8.5 μM for human A375 melanoma cells.
Article
Chemistry, Analytical
Dounia Elfadil, Sara Palmieri, Flavio Della Pelle, Manuel Sergi, Aziz Amine, Dario Compagnone
Summary: This study presents a novel method combining molecularly imprinted polymers (MIPs) and enzymatic inhibition assay for the selective and sensitive determination of acetazolamide (ACZ) in biological samples. The MIPs were synthesized using ACZ as the template molecule and were used as the sorbent phase in dispersive solid-phase extraction (MIPs-dSPE). The developed method showed good recovery and correlation with LC-MS/MS analysis, providing a selective and quantitative approach for the determination of ACZ.
Article
Biochemistry & Molecular Biology
Agne Janoniene, Linas Mazutis, Daumantas Matulis, Vilma Petrikaite
Summary: Inhibition of CA IX by VD11-4-2 decreases movement speed in breast cancer cells without affecting non-cancerous cells. The inhibitor hinders cells from reaching their maximum speed and reduces cell movement towards growth factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Kamil Wojtkowiak, Mariusz Michalczyk, Wiktor Zierkiewicz, Aneta Jezierska, Jaroslaw J. Panek
Summary: This study investigates the non-covalent interactions of Carbonic Anhydrase IX using quantum-chemical approaches, highlighting its significance in cancer treatment and exploring potential anticancer inhibitors. The findings suggest that chalcogen bonding plays a crucial role in conformational stability and free energy mapping of the system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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)
Article
Biochemistry & Molecular Biology
Kai Zhao, Agnes Schaefer, Zhuo Zhang, Katharina Elsaesser, Carsten Culmsee, Li Zhong, Axel Pagenstecher, Christopher Nimsky, Joerg W. Bartsch
Summary: Carbonic anhydrase CA2 is highly expressed in recurrent glioblastoma and temozolomide-resistant glioblastoma stem-like cells (GSCs), promoting cell invasion. The CA2 inhibitor brinzolamide is more effective than the pan-CA inhibitor acetazolamide in sensitizing GSCs to TMZ-induced cell death. The combined treatment of TMZ and brinzolamide induces autophagy in GBM cell lines and GSCs, suggesting a potential treatment strategy for tackling GBM chemoresistance and recurrence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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, Medicinal
Baijayantimala Swain, Santosh Kumar Sahoo, Priti Singh, Andrea Angeli, Venkata Madhavi Yaddanapudi, Claudiu T. Supuran, Mohammed Arifuddin
Summary: A series of novel sulfonamide containing quinoline compounds were synthesized and tested for their inhibitory activity against human carbonic anhydrase isoforms I, II, IX and XII. Most of the compounds showed potent inhibitory activity, with some being more effective than the standard drug acetazolamide. 4-substituted benzenesulfonamides exhibited higher potency than 3-substituted derivatives.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Elena Andreucci, Alessio Biagioni, Sara Peri, Giampaolo Versienti, Fabio Cianchi, Fabio Staderini, Lorenzo Antonuzzo, Claudiu T. Supuran, Erika Olivo, Elisa Pasqualini, Luca Messerini, Daniela Massi, Matteo Lulli, Jessica Ruzzolini, Silvia Peppicelli, Francesca Bianchini, Nicola Schiavone, Lido Calorini, Lucia Magnelli, Laura Papucci
Summary: Gastric cancer is a common malignancy with high mortality rates, mainly due to the development of chemoresistance. Carbonic anhydrase IX (CAIX) has been identified as a potential biomarker associated with poor prognosis in various solid cancers. In this study, it was found that non-responder gastric cancer patients and drug-resistant gastric cancer cell lines showed increased expression of CAIX compared to responder patients and control cells, respectively. Furthermore, a drug called SLC0111 was found to improve the therapy response of both wild-type and resistant gastric cancer cells, suggesting its potential in overcoming chemoresistance.
Article
Nanoscience & Nanotechnology
Wenbao Zuo, Weibin Chen, Jinxue Liu, Shuying Huang, Luping Chen, Qingna Liu, Nian Liu, Quanyi Jin, Yang Li, Peiyuan Wang, Xuan Zhu
Summary: Fe-based nanomaterials with Fenton reaction activity show promise for tumor-specific chemodynamic therapy (CDT). However, low catalytic efficiency and high tumor intracellular pH have limited their clinical application. In this study, macrophage membrane-camouflaged hollow mesoporous ferric oxide (HMFe) nanocatalysts loaded with a carbonic anhydrase IX inhibitor (CAI) were developed to remodel the tumor microenvironment and enhance CDT. The HMFe acted as a Fenton agent with high active-atom exposure, while also providing a hollow cavity for CAI loading. The macrophage membrane-camouflaging improved immune evasion and tumor-specific accumulation, enabling self-amplified CDT and inhibition of tumor metastasis.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Tuba Tekeli, Suleyman Akocak, Andrea Petreni, Nebih Lolak, Servet cete, Claudiu T. Supuran
Summary: By conjugating aromatic aminobenzenesulfonamides with aromatic bis-isocyanates, a series of twelve aromatic bis-ureido-substituted benzenesulfonamides was synthesized. These compounds showed effective inhibitory activity against four human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX, and hCA XII), with selectivity towards hCA IX and hCA XII. The inhibition constants of these compounds ranged from 6.73-835 nM against hCA IX and 5.02-429 nM against hCA XII. Given the importance of hCA IX and hCA XII as drug targets for anti-cancer/anti-metastatic drugs, these inhibitors may have significance in cancer-related studies involving these enzymes.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
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
Neurosciences
Antonia Gurgone, Riccardo Pizzo, Alessandra Raspanti, Giuseppe Chiantia, Sunaina Devi, Debora Comai, Noemi Morello, Federica Pilotto, Sara Gnavi, Leonardo Lupori, Raffaele Mazziotti, Giulia Sagona, Elena Putignano, Alessio Nocentini, Claudiu T. Supuran, Andrea Marcantoni, Tommaso Pizzorusso, Maurizio Giustetto
Summary: Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disease without a cure. The study suggests that modulating the activity of mGluR5 receptors may help improve synaptic, functional, and behavioral defects in CDD patients. The findings indicate that mGluR5 receptors could be a potential therapeutic target for CDD.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Laura De Luca, Andrea Angeli, Federico Ricci, Claudiu T. Supuran, Rosaria Gitto
Summary: In recent years, the use of multistep hybrid computational protocols in drug discovery of enzyme inhibitors has gained attention. This study successfully generated pharmacophore models for hCA VA inhibitors using a combination of ligand- and structure-based approaches. Virtual screening on a database of commercially available sulfonamides resulted in the identification of several potential inhibitors.
ARCHIV DER PHARMAZIE
(2023)
Article
Chemistry, Medicinal
Annachiara Tinivella, Jerome C. Nwachukwu, Andrea Angeli, Francesca Foschi, Anna Laura Benatti, Luca Pinzi, Tina Izard, Marta Ferraroni, Rangarajan Erumbi, Michael S. Christodoulou, Daniele Passarella, Claudiu T. Supuran, Kendall W. Nettles, Giulio Rastelli
Summary: In this study, a ligand-based and structure-based multi-target repurposing strategy was used to investigate hexahydrocyclopenta[c]quinoline compounds. Human Carbonic Anhydrases (hCA) and Estrogen Receptors (ER) were identified as top candidates for dual modulation. Two new compounds were designed and synthesized, which directly modulate the activities of both hCA and ER. These compounds showed potent inhibition of cancer cell proliferation and selectivity for different cell types. This study lays the foundation for optimizing the multi-target activity of hCA and ER.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Chemistry, Medicinal
Claudiu T. Supuran
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Emanuela Berrino, Laura Micheli, Simone Carradori, Lorenzo di Cesare Mannelli, Paolo Guglielmi, Alessandro De Luca, Fabrizio Carta, Carla Ghelardini, Daniela Secci, Claudiu T. Supuran
Summary: This study proposes a novel approach to relieve pain in patients with rheumatoid arthritis by combining carbonic anhydrase inhibitors (CAIs) and CO releasing molecules (CORMs). The resulting CAI-CORM hybrids exhibit strong anti-inflammatory effects in in vitro disease models and relieve pain symptoms in an in vivo RA rat model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Andrea Angeli, Laura Micheli, Fabrizio Carta, Marta Ferraroni, Tracey Pirali, Asia Fernandez Carvajal, Antonio Ferrer Montiel, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Claudiu T. Supuran
Summary: We have reported a series of compounds that have the potential to manage oxaliplatin-induced neuropathy (OINP) by modulating human Carbonic Anhydrases (hCAs) and Transient Receptor Potential Vanilloid 1 (TRPV1). These compounds showed effective inhibition activity against the main hCAs involved in OINP in vitro, and some of them exhibited moderate agonism of TRPV1. In vivo evaluation of promising derivatives demonstrated potent and persistent antihypersensitivity effects in a mouse model of OINP.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Belma Zengin Kurt, Gulsen Celebi, Dilek Ozturk Civelek, Atilla Akdemir, Andrea Angeli, Fatih Sonmez, Claudiu T. Supuran
Summary: In this study, sixty novel coumarin-monoterpene compounds were synthesized and evaluated for their inhibitory effects on hCA isoforms and anticancer potentials. All synthesized molecules selectively inhibited CA IX and XII, with compounds 23 and 42 showing the strongest inhibitory activity against hCA IX. Cytotoxicity evaluation revealed that compounds 14 and 63 exhibited the highest cytotoxicity on MCF-7 cells, while compound 23 showed the strongest cytotoxic effect on both PC-3 and HT-29 cell lines. Furthermore, compounds 14, 23, and 66 showed a reduction in CA IX and CA XII protein expression and increased apoptosis in different cell lines. The modeling studies demonstrated that only the open coumarin form of the compounds could interact directly with the active-site Zn2+ ion.
Review
Chemistry, Medicinal
Francesco Melfi, Simone Carradori, Cristina Campestre, Entela Haloci, Alessandra Ammazzalorso, Rossella Grande, Ilaria D'Agostino
Summary: This review provides an overview of the recent advances in the discovery of new inhibitors and biological targets for the treatment of Human African Trypanosomiasis. It also discusses the development of new vaccines and formulations. The findings of this study are valuable for the search of new therapeutic options for this neglected disease.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Article
Biochemistry & Molecular Biology
Simone Carradori, Andrea Angeli, Patrick S. Sfragano, Xheila Yzeiri, Massimo Calamante, Damiano Tanini, Antonella Capperucci, Hannah Kunstek, Mihayl Varbanov, Clemente Capasso, Claudiu T. Supuran
Summary: In this study, new heptamethine-based compounds decorated with a sulfonamide moiety were synthesized for selectively inhibiting bacterial carbonic anhydrases (CAs) and being photoactivated by specific wavelengths. The compounds showed potent CA inhibition and a slight preference for bacterial isoforms. They also exhibited promising effects against S. epidermidis under irradiation, while being non-cytotoxic to human red blood cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shaik Mahammad Ghouse, Kavyaraj Bahatam, Andrea Angeli, Gaurav Pawar, Krishna Kartheek Chinchilli, Venkata Madhavi Yaddanapudi, Arifuddin Mohammed, Claudiu T. Supuran, Srinivas Nanduri
Summary: Carbonic anhydrase isoforms IX and XII play a crucial role in regulating pH in hypoxic tumors and promoting the metastasis of solid tumors. Selective inhibitors targeting these isoforms can reduce their activity, providing an anti-tumor and anti-metastatic mechanism. Coumarin-based derivatives are selective inhibitors of CA isoforms IX and XII. In this study, new 3-substituted coumarin derivatives were designed and synthesized, and their inhibitory activity against various carbonic anhydrase isoforms was evaluated. Tertiary sulphonamide derivative 6c showed selective inhibition against CA IX, while carbothioamides 7c, 7b, and oxime ether derivative 20a exhibited good inhibition against both CA IX and CA XII. The binding mode was predicted and validated using molecular docking and dynamic simulations.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Nora Astrain-Redin, Niccolo Paoletti, Daniel Plano, Alessandro Bonardi, Paola Gratteri, Andrea Angeli, Carmen Sanmartin, Claudiu T. Supuran
Summary: In the search for new cancer treatments, organoselenium compounds and carbonic anhydrase inhibitors have shown promise. Selenium-containing compounds, especially selenols, have demonstrated potent inhibition of tumor-associated CA isoforms. In this study, selenoesters combining NSAIDs and natural product fragments were evaluated as nonclassical inhibitors of tumor-associated CA isoforms.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Claudiu T. Supuran
Summary: Carbonic anhydrases play important roles in bacteria and targeting them could lead to the development of novel antibacterials without drug resistance problems. Significant advances have been made in designing effective inhibitors for various bacterial CAs, with in vivo validation for some pathogens.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Chemistry, Medicinal
Lalit Vats, Priyanka Arya, Rajiv Kumar, Simone Giovannuzzi, Neera Raghav, Claudiu T. Supuran, Pawan K. Sharma
Summary: This study synthesized and tested 28 novel compounds for their inhibition potential against cathepsin B and hCA isoforms, and found that one compound exhibited better and more selective inhibition against the cancer-associated hCA IX.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Anastasija Balasova, Aleksandrs Pustenko, Alessio Nocentini, Daniela Vullo, Claudiu T. Supuran, Raivis Zalubovskis
Summary: A range of 3H-1,2-benzoxaphosphepine 2-oxide aryl derivatives were synthesized in five steps from salicylaldehydes. These compounds showed selective inhibition against cancer-associated CA IX and XII, with the fluorine-containing analogues being the most potent inhibitors. SAR analysis indicated that 7- and 8-substituted aryl derivatives were more effective inhibitors of CA IX and XII than 9-substituted derivatives.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
