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
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
Biochemistry & Molecular Biology
Toni C. Denner, Andrea Angeli, Marta Ferraroni, Claudiu T. Supuran, Rene Csuk
Summary: Sulfonamides have inhibitory effects on carbonic anhydrases, and sulfonamides with biphenyl- and benzylphenyl substitutions show high selectivity for the treatment of hypoxic cancers and potential applications in treating cerebral edema.
Article
Biochemistry & Molecular Biology
Hany S. Ibrahim, Mohamed A. Abdelrahman, Alessio Nocentini, Silvia Bua, Hatem A. Abdel-Aziz, Claudiu T. Supuran, Sahar M. Abou-Seri, Wagdy M. Eldehna
Summary: In this study, the effect of combining zinc-binding sulfonamide and carboxylic acid groups on the inhibitory potency and selectivity of carbonic anhydrase (CA) inhibitors was investigated. The results showed that the coumarin derivatives with zinc-binding sulfonamide group showed strong inhibitory activity against tumor-associated CA isoforms, while the ones with carboxylic acid group exhibited weaker inhibitory activity. Interestingly, coumarin derivatives without zinc-binding group displayed high selectivity towards CA isoforms IX and XII over other off-target isoforms.
BIOORGANIC CHEMISTRY
(2022)
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
Andrea Angeli, Victor Kartsev, Anthi Petrou, Mariana Pinteala, Volodymyr Brovarets, Roman Vydzhak, Svitlana Panchishin, Athina Geronikaki, Claudiu T. Supuran
Summary: A series of novel benzenesulfonamides incorporating pyrazole- and pyridazinecarboxamides decorated with bulky moieties were synthesized and investigated for their inhibitory effects on various human carbonic anhydrase isoforms. Isoform-selective inhibitors were obtained, with a computational approach employed to explain the observed selectivity, potentially useful in drug design for developing inhibitors with pharmacological applications such as antiglaucoma, diuretic, antitumor, or anti-cerebral ischemia drugs.
Article
Crystallography
Yassine Aimene, Romain Eychenne, Frederic Rodriguez, Sonia Mallet-Ladeira, Nathalie Saffon-Merceron, Jean-Yves Winum, Alessio Nocentini, Claudiu T. Supuran, Eric Benoist, Achour Seridi
Summary: In this work, two classes of Carbonic Anhydrase inhibitors, sulfonamide and coumarin derivatives, were synthesized and evaluated for their inhibitory activity against hCA isoforms. The compounds showed high selectivity and potential anti-cancer properties, with coumarin derivatives demonstrating strong inhibition against tumor-associated isoforms. Molecular docking calculations were performed to rationalize the results and investigate the inhibition profiles at the tumor-associated CA active site.
Article
Chemistry, Multidisciplinary
Tayfun Arslan, Murat Senturk, Lutfi Karagoz, Yalcin Karagoz, Deniz Ekinci, Asiye Efe, Emir Alper Turkoglu, Fikriye Uras
Summary: The inhibition profiles of synthesized 4-methyl benzene sulfonamide derivatives on various enzymes were investigated in this study. The results showed that these compounds exhibited different levels of inhibition on the target enzymes, indicating their potential as drug candidates. Molecular docking studies further elucidated the mechanism of action of these inhibitors on the enzymes.
Article
Biochemistry & Molecular Biology
Moataz Shaldam, Alessio Nocentini, Zainab M. Elsayed, Tamer M. Ibrahim, Rofaida Salem, Ramadan A. El-Domany, Clemente Capasso, Claudiu T. Supuran, Wagdy M. Eldehna
Summary: A new series of quinoline-based benzenesulfonamides (QBS) have been developed as potential carbonic anhydrase inhibitors, with para-sulphonamide derivatives showing the best inhibitory activity. In addition, a linker elongation approach and molecular docking simulation studies were used to further investigate the anticancer effects of QBS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Suleyman Akocak, Nebih Lolak, Simone Giovannuzzi, Claudiu T. Supuran
Summary: This research introduces a series of compounds that exhibit significant inhibitory activity against tumor-associated isoforms of carbonic anhydrase, with certain selectivity. Investigating the structure-activity relationships of these compounds could provide insights for the development of novel therapeutic agents targeting hypoxic tumors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Simon L. Durr, Andrea Levy, Ursula Rothlisberger
Summary: The authors propose a model based on 3D convolutional networks to predict the location of zinc in experimental and computationally predicted structures. This study is important because it improves the accuracy of zinc ion location prediction in protein structures.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Chnar Kakakhan, Cuneyt Turkes, Ozcan Gulec, Yeliz Demir, Mustafa Arslan, Gizem Ozkemahli, Sukru Beydemir
Summary: A series of novel inhibitors of human alpha-carbonic anhydrase (hCA) were designed using a tail approach. These inhibitors showed remarkable selectivity for tumor isoforms hCA IX and XII. Adding a lipophilic naphthyl tail to the analogues increased the inhibitory and selective activities against hCA XII. The compounds also exhibited inhibitory effects against a human lung adenocarcinoma cancer cell line.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Samar A. El-Kalyoubi, Ehab S. Taher, Tarek S. Ibrahim, Mohammed Farrag El-Behairy, Amany M. M. Al-Mahmoudy
Summary: A series of quinoline-uracil hybrids were synthesized and studied for their inhibitory activity and selectivity against multiple enzyme isoforms. Compound 101 showed the best performance in terms of inhibitory activity and selectivity.
Article
Chemistry, Medicinal
Erden Banoglu, Taner Ercanli, Tugce Gur Maz, Daniela Vullo, Alessandro Bonardi, Paola Gratteri, Claudiu T. Supuran
Summary: A series of newly synthesized thiadiazolyl-benzenesulfonamide derivatives exhibited significant inhibitory activity against human carbonic anhydrase, with some compounds showing dual inhibition against two isoforms. The nature of substituents at the tail part of the main scaffold influenced the activity and selectivity towards different isoforms, with compound 17 demonstrating the most potent inhibitory effects.
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
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)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
