Article
Chemistry, Medicinal
Ozlem Akgul, Andrea Angeli, Silvia Selleri, Clemente Capasso, Claudiu T. Supuran, Fabrizio Carta
Summary: New taurultambenzenesulfonamides were synthesized and evaluated for their inhibitory activity against multiple Carbonic Anhydrases. Some compounds showed potent inhibition against VchCA alpha and BpsCA-gamma, indicating potential for the development of new generation CA-based antibiotics.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Aftab Nadeem, Raghavendra Nagampalli, Eric Toh, Athar Alam, Si Lhyam Myint, Thomas Heidler, Mitesh Dongre, Nikola Zlatkov, Hudson Pace, Fouzia Bano, Anders Sjostedt, Marta Bally, Bernt Eric Uhlin, Sun Nyunt Wai, Karina Persson
Summary: MakA protein is part of a gene cluster in Vibrio cholerae, along with other proteins forming a tripartite cytolytic toxin that is toxic to both red blood cells and human colon carcinoma cells. This previously unrecognized toxin may contribute to fitness and virulence potential in different host environments and organisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Marialuigia Fantacuzzi, Ilaria D'Agostino, Simone Carradori, Francesco Liguori, Fabrizio Carta, Mariangela Agamennone, Andrea Angeli, Filomena Sannio, Jean-Denis Docquier, Clemente Capasso, Claudiu T. Supuran
Summary: Vibrio cholerae, a pathogen responsible for life-threatening infections in low-income countries, has developed resistance to antibacterial drugs. Researchers have identified carbonic anhydrases (CAs) encoded by V. cholerae as potential pharmacological targets. They have developed a large library of CAs inhibitors with different flexibility degrees and found compounds with strong inhibition against Vch alpha CA. Computational studies have provided insights into the inhibitory activity and isoform selectivity of these compounds.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biology
Yoshihisa Hirakawa, Miki Senda, Kodai Fukuda, Hong Yang Yu, Masaki Ishida, Masafumi Taira, Kazushi Kinbara, Toshiya Senda
Summary: COG4337 proteins are a novel metal-independent variant of iota-class carbonic anhydrases, which accelerate CO2 hydration and are localized in organelles for CO2 metabolism. They share structural features with iota-class CAs but exhibit activity without reliance on metals.
Article
Immunology
Huihui Sun, Ming Liu, Fenxia Fan, Zhe Li, Yufeng Fan, Jingyun Zhang, Yuanming Huang, Zhenpeng Li, Jie Li, Jialiang Xu, Biao Kan
Summary: This study investigated the infection mechanism of lytic phage VP2 on Vibrio cholerae and found that the type II secretory system plays a significant role in this process.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Review
Microbiology
Laura Alvarez, Sara B. Hernandez, Felipe Cava
Summary: The cell wall of most bacteria, composed of peptidoglycan, plays a crucial role in protecting them from environmental stressors. Vibrio cholerae has become a major model for studying cell wall genetic determinants, regulatory links, and adaptive mechanisms, shedding light on novel insights. This review provides a comprehensive overview of V. cholerae's cell wall biology and genetics, emphasizing the similarities and differences with Escherichia coli.
ANNUAL REVIEW OF MICROBIOLOGY, VOL 75, 2021
(2021)
Article
Chemistry, Medicinal
Silvia Salerno, Giorgio Amendola, Andrea Angeli, Emma Baglini, Elisabetta Barresi, Anna Maria Marini, Rahul Ravichandran, Monica Viviano, Sabrina Castellano, Ettore Novellino, Federico Da Settimo, Claudiu T. Supuran, Sandro Cosconati, Sabrina Taliani
Summary: Carbonic Anhydrases (CAs) are important targets for treating various disease conditions, but the difficulty lies in finding potential drugs due to their ubiquitous localization and high homology. By synthesizing new bicyclic tetrahydroindazoles and conducting biological evaluations and theoretical studies, a new platform for the discovery of isotype selective CA inhibitors has been identified.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Simone Giovannuzzi, Chad S. Hewitt, Alessio Nocentini, Clemente Capasso, Gabriele Costantino, Daniel P. Flaherty, Claudiu T. Supuran
Summary: The inhibition of alpha-class carbonic anhydrases (CAs) from bacterial pathogens by phenols and phenolic acids was investigated. Small changes in the phenol scaffold led to drastic effects on the inhibitory activity of bacterial CA. This underinvestigated class of bacterial CA inhibitors may have potential in fighting drug resistant bacteria.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Aytug Okumus, Gamze Elmas, Arzu Binici, Ekrem Tunca, Tuncer Hokelek, Zeynel Kilic
Summary: Starting phosphazenes (1 and 2) were synthesized by substituting hexachlorocyclotriphosphazene (HCCP) with N-(4-fluorobenzyl)-1,3-diaminopropane (L1) and N,N’-bis(4-fluorobenzyl)-1,3-diaminopropane (L2), respectively. Tetraaminomono- and bis-(4-fluorobenzyl)spiro(N/N)cyclotriphosphazenes (1a, 1b, 2a, and 2b) were prepared through condensation reactions. The structures of the new products were identified using various analytical techniques, and compound 2b was found to have a stronger inhibitory effect on esterase activities compared to compound 2a.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Hiroya Oki, Kazuki Kawahara, Minato Iimori, Yuka Imoto, Haruka Nishiumi, Takahiro Maruno, Susumu Uchiyama, Yuki Muroga, Akihiro Yoshida, Takuya Yoshida, Tadayasu Ohkubo, Shigeaki Matsuda, Tetsuya Iida, Shota Nakamura
Summary: Colonization is a crucial step in Vibrio cholerae infection. The interaction between the minor pilin and the secreted protein plays a key role in this process, and it could be a potential therapeutic target.
Article
Biochemistry & Molecular Biology
Md Rajib Sharker, Zahid Parvez Sukhan, Kanij Rukshana Sumi, Sang Ki Choi, Kap Seong Choi, Kang Hee Kho
Summary: Carbonic anhydrases (CAs) are a type of metalloenzymes that catalyze the reversible interconversion of CO2/HCO3- and are widely present in both prokaryotes and eukaryotes. In this study, a CA II (HdhCA II) was sequenced and characterized from the mantle tissue of the Pacific abalone, suggesting a potential role in shell formation of abalone.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yeliz Kaya, Ayse Ercag, Yunus Zorlu, Yeliz Demir, Ilhami Gulcin
Summary: By synthesizing Pd(II) complexes and evaluating their inhibitory activity, it was found that asymmetric isatin bisthiocarbohydrazone ligands can effectively inhibit acetylcholinesterase and carbonic anhydrase I, II.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Francesca Mancuso, Andrea Angeli, Viviana De Luca, Federica Bucolo, Laura De Luca, Clemente Capasso, Claudiu T. Supuran, Rosaria Gitto
Summary: This study reports on the screening process of inhibitors targeting carbonic anhydrases expressed in bacteria. By studying the inhibitory effects and selectivity of newly synthesized analogs, it was found that simple structural modifications can have a significant impact on inhibition and selectivity. Although the best active inhibitors showed high activity against bacterial carbonic anhydrases, they demonstrated a loss of selectivity towards human isozymes, highlighting the need for further development of more promising inhibitors.
ARCHIV DER PHARMAZIE
(2022)
Article
Immunology
Xianqin Song, Yu Song, Quanping Ma, Kehua Fang, Xiaotian Chang
Summary: This study found that M1 macrophages can increase the expression of CA1 and CA2 to promote atherosclerotic calcification in vascular smooth muscle cells (VSMCs) by secreting TNF-a.
JOURNAL OF INFLAMMATION RESEARCH
(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
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
Chemistry, Multidisciplinary
Giulia Vanti, Laura Micheli, Emanuela Berrino, Lorenzo Di Cesare Mannelli, Irene Bogani, Fabrizio Carta, Maria Camilla Bergonzi, Claudiu T. Supuran, Carla Ghelardini, Anna Rita Bilia
Summary: In this study, a thermosensitive gel incorporating escinosomes, innovative nanovesicles made of escin, stabilized with tween 20 and loaded with a Carbonic Anhydrase Inhibitor (CAI) bearing a Carbon Monoxide Releasing Moiety (CORM) was developed. The gel showed optimal physical parameters and high drug encapsulation efficiency. In vivo experiments demonstrated that the gel could effectively relieve pain and improve motor impairments in a rat model of rheumatoid arthritis.
JOURNAL OF CONTROLLED RELEASE
(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
Moataz A. Shaldam, Ahmed F. Khalil, Hadia Almahli, Maiy Y. Jaballah, Andrea Angeli, Eman F. Khaleel, Rehab Mustafa Badi, Eslam B. Elkaeed, Claudiu T. Supuran, Wagdy M. Eldehna, Haytham O. Tawfik
Summary: New 5-cyano-6-oxo-pyridine-based sulfonamides were designed and synthesized to potentially inhibit both EGFR and CA, with anticancer properties. The inhibitory effects on EGFR were observed, while the inhibitory effects on CA were affected by the neighboring methoxy group.
ARCHIV DER PHARMAZIE
(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)
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)