Article
Biochemistry & Molecular Biology
Chandra Bhushan Mishra, Raj Kumar Mongre, Amresh Prakash, Raok Jeon, Claudiu T. Supuran, Myeong-Sok Lee
Summary: BSM-0004, a novel hCA IX inhibitor, demonstrated potent anticancer effects in breast cancer cells by inducing apoptosis. It also significantly regulated the expression of crucial biomarkers associated with apoptosis. Moreover, in vivo studies showed that BSM-0004 effectively reduced tumor growth in a xenograft cancer model.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Heba T. Abdel-Mohsen, Ahmed M. El Kerdawy, Mohamed A. Omar, Andrea Petreni, Rasha M. Allam, Hoda El Diwani, Claudiu T. Supuran
Summary: A novel series of carbonic anhydrase inhibitors showed high potency and selectivity, displaying significant antiproliferative activity against cancer cells and suggesting CA II inhibition as a potential alternative therapeutic target for cancer treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Mostafa M. Elbadawi, Wagdy M. Eldehna, Alessio Nocentini, Warda R. Somaa, Sara T. Al-Rashood, Eslam B. Elkaeed, Mahmoud A. El Hassab, Hatem A. Abdel-Aziz, Claudiu T. Supuran, Mohamed Fares
Summary: In this study, tail/dual tail approaches were used to design and synthesize benzenesulfonamide derivatives as new SLC-0111 analogs with carbonic anhydrase (CA) inhibitory activity. The results showed that these derivatives had varying effects on different CA isoforms. Appending a second hydrophilic tail significantly enhanced the inhibitory activities towards hCA IX and hCA XII isoforms. SAR analysis revealed the importance of grafting the sulfamoyl functionality at para-position and incorporating a bulky hydrophobic tail for CA inhibitory activity. The most potent hCA IX inhibitors exhibited strong cell growth inhibitory activity against breast cancer cell lines.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
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
Haytham O. Tawfik, Moataz A. Shaldam, Alessio Nocentini, Rofaida Salem, Hadia Almahli, Sara T. Al-Rashood, Claudiu T. Supuran, Wagdy M. Eldehna
Summary: Carbonic anhydrases (CAs) are potential targets for developing anticancer agents. This study focuses on designing selective inhibitors for cancer-related hCA IX/XII isoforms, and a new series of coumarin derivatives were synthesized for this purpose. The results show that the prepared coumarins displayed inhibition activity on hCA IX/XII isoforms and exhibited antitumor activity on NCI-59 human cancer types.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Shubham Kumar, Sandeep Rulhania, Shalini Jaswal, Vikramdeep Monga
Summary: Carbonic anhydrase is an important enzyme involved in various physiological and pathological processes, with 16 different isoforms in humans. Inhibitors targeting different isoforms of carbonic anhydrase have clinical applications in treating various diseases, but current drugs lack selectivity leading to undesired side effects. Efforts are being made to develop novel isoform-selective inhibitors of carbonic anhydrase for therapeutic implications.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Morteza Abdoli, Viviana De Luca, Clemente Capasso, Claudiu T. Supuran, Raivis Zalubovskis
Summary: A series of novel compounds were synthesized and evaluated for their inhibition of eukaryotic and human carbonic anhydrases. The results showed good inhibition against some target enzymes and weaker inhibition against others. These findings are important for the search for potential antifungal drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Andrea Angeli, Victor Kartsev, Anthi Petrou, Mariana Pinteala, Volodymyr Brovarets, Sergii Slyvchuk, Stepan Pilyo, Athina Geronikaki, Claudiu T. Supuran
Summary: Carbonic anhydrases play a crucial role in living organisms and a series of new compounds were synthesized and tested as potential inhibitors in this study. Some of the derivatives showed interesting inhibitory activity towards tumor-associated isoforms. Computational procedures were also used to investigate the binding mode of these compounds within the active site.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Morteza Abdoli, Claudiu T. Supuran, Raivis Zalubovskis
Summary: A small library of substituted cyclic guanidine incorporated benzothiazole-6-sulphonamides was synthesized and evaluated for their inhibitory activity against brain-associated human carbonic anhydrase isoforms. The results demonstrated that these compounds exhibited potent and selective inhibition towards hCA II and VII, while hCA I showed lower sensitivity to inhibition. These derivatives may serve as promising candidates for the design of more potent and selective hCA II and VII inhibitors.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Amarjyoti Das Mahapatra, Aarfa Queen, Mohd Yousuf, Parvez Khan, Afzal Hussain, Md. Tabish Rehman, Mohamed F. Alajmi, Bhaskar Datta, Md. Imtaiyaz Hassan
Summary: Inhibitors of carbonic anhydrase have the potential to address various diseases. This research focuses on developing a new scaffold, oxazole-5(4H)-one derivatives, for the selective inhibition of human carbonic anhydrase VA (hCAVA). Two compounds show high binding affinity and inhibit the expression of CAVA and GLUT4 in adipocytes.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Weiwei An, Katrina J. Holly, Alessio Nocentini, Ryan D. Imhoff, Chad. S. Hewitt, Nader S. Abutaleb, Xufeng Cao, Mohamed N. Seleem, Claudiu T. Supuran, Daniel P. Flaherty
Summary: This paper discusses the inhibition mechanism and effects of the inhibitor acetazolamide (AZM) and its analogs against vancomycin-resistant enterococci (VRE), as well as the research methods related to binding to different enzymes and selectivity.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Rehab F. Ahmed, Walaa R. Mahmoud, Nagwa M. Abdelgawad, Marwa A. Fouad, Mona F. Said
Summary: This study designed a series of novel carbonic anhydrase inhibitors and evaluated their inhibitory activity and anticancer activity. Compounds 4b, 5b, 5d, 5e, 6b, 9b, 9e, and 11b showed significant inhibitory activity against both CA isoforms, while compound 6e exhibited significant cytostatic activity against multiple cancer cell lines, suggesting its potential as a promising anticancer drug.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Heba T. Abdel-Mohsen, Mohamed A. Omar, Andrea Petreni, Claudiu T. Supuran
Summary: A series of 2-thioquinazoline-benzenesulfonamide hybrids were designed as carbonic anhydrase inhibitors. Compounds 12f and 12p exhibited potent inhibitory activity, with high selectivity for specific cell lines.
ARCHIV DER PHARMAZIE
(2022)
Article
Biochemistry & Molecular Biology
Baijayantimala Swain, Abrar Khan, Priti Singh, Vaibhav S. Marde, Andrea Angeli, Krishna Kartheek Chinchilli, Venkata Madhavi Yaddanapudi, Simone Carradori, Claudiu T. Supuran, Mohammed Arifuddin
Summary: A series of novel rhodamine-linked benzenesulfonamide derivatives were synthesized and screened for their inhibitory action against human carbonic anhydrase isoforms. These compounds showed good to excellent inhibition against all tested isoforms, with slightly higher selectivity towards hCA IX and XII compared to hCA I and II.
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
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
Vikas Sharma, Rajiv Kumar, Andrea Angeli, Claudiu T. Supuran, Pawan K. Sharma
Summary: In this study, a series of novel 1,2,3-triazole benzenesulfonamide compounds were designed and synthesized, and their inhibitory effects on human carbonic anhydrase were tested. The results showed that these compounds displayed variable inhibition constants against different isoforms of carbonic anhydrase, with some compounds exhibiting strong inhibitory potency. Computational simulations revealed the interactions between these compounds and the binding sites of carbonic anhydrase. The study emphasizes the importance of the synthesized 1,2,3-triazole compounds as building blocks for developing carbonic anhydrase inhibitor drugs.
ARCHIV DER PHARMAZIE
(2023)
Editorial Material
Chemistry, Medicinal
Claudiu T. Supuran
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Andrea Angeli, Anthi Petrou, Victor Kartsev, Boris Lichitsky, Andrey Komogortsev, Clemente Capasso, Athina Geronikaki, Claudiu T. Supuran
Summary: Carbonic anhydrases play a crucial role in the CO2 hydration reaction in all living organisms and have potential as antiinfective targets. Griseofulvin and usnic acid sulfonamides were synthesized and evaluated as potential CA inhibitors. These compounds showed interesting inhibitory activity against various isoforms of CA, as well as a fungal enzyme. Computational studies were performed to understand the binding mode of these compounds in the active site of human CAs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
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)
Article
Chemistry, Medicinal
Ilaria D'Agostino, Susi Zara, Simone Carradori, Viviana De Luca, Clemente Capasso, Clemens H. M. Kocken, Anne-Marie Zeeman, Andrea Angeli, Fabrizio Carta, Claudiu T. Supuran
Summary: The hybrid compounds synthesized in this study, which combine the Artesunate core with a sulfonamide moiety, showed high inhibition potency against the protozoan PfCA, while exhibiting low cytotoxic effects on human cells, indicating a wide therapeutic window.
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)
Editorial Material
Chemistry, Medicinal
Francesco Fiorentino, Fabrizio Carta, Dante Rotili, Antonello Mai, Claudiu T. Supuran
FUTURE MEDICINAL CHEMISTRY
(2023)
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)
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)
Article
Biochemistry & Molecular Biology
Deepak Shilkar, Mohd Usman Mohd Siddique, Silvia Bua, Sabina Yasmin, Mrunali Patil, Ajay Kumar Timiri, Claudiu T. Supuran, Venkatesan Jayaprakash
Summary: A series of phthalimide-capped benzene sulphonamides (1-22) were evaluated for their inhibitory activity against carbonic anhydrase I (hCA I) and carbonic anhydrase II (hCA II). Compound 1 showed potent inhibitory activity against both hCA I (Ki = 28.5 nM) and hCA II (Ki = 2.2 nM), with 10 and 6 times higher potency than the standard inhibitor, acetazolamide. Molecular docking and MD simulations were performed to understand the atomic level interactions responsible for the selectivity of compound 1 towards hCA II.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Andrea Angeli, Marta Ferraroni, Carlotta Granchi, Filippo Minutolo, Xiaozhuo Chen, Pratik Shriwas, Emilio Russo, Antonio Leo, Silvia Selleri, Fabrizio Carta, Claudiu T. Supuran
Summary: In this study, a set of compounds with glucosyl and galactosyl moieties were designed and developed. Their ability to enhance GLUT1 mediated glucose intake in non-small-cell lung cancer cells and inhibit carbonic anhydrase isoforms associated with uncontrolled seizures in epilepsy was evaluated. The binding mode of compound 8 with hCA II was determined by X-ray crystallography. Among the selected derivatives, compound 4b effectively suppressed the occurrence of uncontrolled seizures in an in vivo induced maximal electroshock model, providing a novel pharmacological approach for managing GLUT1-DS associated diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Marjan Sobati, Morteza Abdoli, Alessandro Bonardi, Paola Gratteri, Claudiu T. Supuran, Raivis Zalubovskis
Summary: A series of novel sulfonamide-incorporated α-aminophosphonate derivatives were synthesized, utilizing a one-pot, two-step FeCl3-catalyzed coupling reaction. These compounds were tested for inhibition against four different isoforms of carbonic anhydrase, including human cytosolic (h) hCA I and II (off-targets), as well as transmembrane cancer-related hCA IX and XII (targets). Among the synthesized compounds, derivative 23 exhibited the highest selectivity towards the cancer-associated isoforms over the off-target hCA I and hCA II, and the binding mode of both enantiomers R and S was investigated using in silico studies.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)