Article
Biochemistry & Molecular Biology
Arne Rotermund, Sarah Brandt, Martin S. Staege, Jana Luetzkendorf, Lutz P. Mueller, Thomas Mueller
Summary: Tumor-associated carbonic anhydrases IX (CAIX) and XII (CAXII) have shown potential as targets for anti-cancer therapy, with the CAIX/CAXII specific inhibitor SLC-0111 passing clinical phase I study. There is a unique CMS-related CAIX/CAXII expression pattern in colorectal cancer (CRC), suggesting that patients with CMS3-classified tumors would benefit the most from treatment targeting CAIX/CAXII.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Chemistry, Medicinal
Davide Ialongo, Antonella Messore, Valentina Noemi Madia, Valeria Tudino, Alessio Nocentini, Paola Gratteri, Simone Giovannuzzi, Claudiu T. T. Supuran, Alice Nicolai, Susanna Scarpa, Samanta Taurone, Michele Camarda, Marco Artico, Veronica Papa, Francesco Saccoliti, Luigi Scipione, Roberto Di Santo, Roberta Costi
Summary: Solid tumors create a hostile environment for surrounding cells by decreasing pH through producing metabolic acids. Carbonic anhydrases (CAs) play a role in acid/base regulation and are clinically relevant in cancer therapy. This study describes new diketo acid derivatives as nanomolar inhibitors of the CA IX and XII isoforms, with selectivity over CAs I and II. These compounds showed antiproliferative activity in tumor cell lines overexpressing CA IX and XII, with no effect on normal cells.
Article
Oncology
Annachiara Sarnella, Ylenia Ferrara, Luigi Auletta, Sandra Albanese, Laura Cerchia, Vincenzo Alterio, Giuseppina De Simone, Claudiu T. Supuran, Antonella Zannetti
Summary: The study demonstrates that using the CA IX/XII specific inhibitor SLC-0111 can enhance the sensitivity of HNSCC to cisplatin, reducing proliferation, migration, and invasion of cells. Furthermore, combination therapy can inhibit the activation of cell signaling pathways such as STAT3, AKT, ERK, and EMT program, while inducing apoptosis in cancer cells.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Pavitra S. Thacker, Arifuddin Mohammed, Claudiu T. Supuran, Prerna L. Tiwari, Nerella S. Goud, Danaboina. Srikanth, Andrea Angeli
Summary: A series of coumarin carboxamides were synthesized and tested for their inhibitory activity against hCA isoforms. The results showed that these compounds selectively inhibited isoforms IX and XII, with 6a and 6b exhibiting the most potent inhibitory activity. These compounds may serve as valuable starting points for the design and development of selective and potent hCA IX and XII inhibitors.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Eva Havrankova, Vladimir Garaj, Sarka Mascaretti, Andrea Angeli, Zuzana Soldanova, Miroslav Kemka, Jozef Motycka, Marie Brazdova, Jozef Csoellei, Josef Jampilek, Claudiu T. Supuran
Summary: A series of potential human carbonic anhydrase inhibitors were synthesized and evaluated for their inhibition of different isoenzymes. Some compounds showed significant effects on hCA IX isoenzyme and demonstrated good activity against vancomycin-resistant Enterococcus faecalis (VRE).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Simone Giovannuzzi, Clemente Capasso, Alessio Nocentini, Claudiu T. Supuran
Summary: A series of new sulfocoumarins with different substitutions were synthesized and screened as prodrug inhibitors of cancer-associated carbonic anhydrases. Sulfocoumarin 15 was found to be the most potent and selective inhibitor.
Review
Biochemistry & Molecular Biology
Anna Di Fiore, Claudiu T. Supuran, Andrea Scaloni, Giuseppina De Simone
Summary: This review summarizes existing literature data on the post-translational modifications of hCA IX and hCA XII, emphasizing their specific role in cancer pathological processes. Limited data are currently available on these modifications and their functional implication in the tumor environment.
Article
Chemistry, Physical
Adel I. Alalawy, Kahdr Alatawi, Noof A. Alenazi, Ahmad Fawzi Qarah, Omar M. Alatawi, Rua B. Alnoman, Arwa Alharbi, Nashwa M. El-Metwaly
Summary: A series of new substituted thiophene and their corresponding thiophene-pyrazole analogues-based benzene sulfonamide were synthesized and characterized. The structural and energetic properties of the synthesized compounds were explored. The derivatives showed potential anticancer activity and inhibitory effects on specific enzymes.
JOURNAL OF MOLECULAR STRUCTURE
(2024)
Article
Biochemistry & Molecular Biology
Arzu Gumus, Murat Bozdag, Atilla Akdemir, Andrea Angeli, Silvia Selleri, Fabrizio Carta, Claudiu T. Supuran
Summary: A novel series of thiosemicarbazide-substituted coumarins were synthesized and showed selective activities against tumor-associated carbonic anhydrase isoforms IX and XII. Molecular modeling studies suggested multiple interactions within the enzymatic cavity, potentially explaining the high potency and selectivity.
Article
Biochemistry & Molecular Biology
Davide Moi, Serena Vittorio, Andrea Angeli, Gianfranco Balboni, Claudiu T. Supuran, Valentina Onnis
Summary: A series of hydrazonobenzenesulfonamides were designed, synthesized and evaluated for their inhibitory activity against human carbonic anhydrase (hCA) isoforms. The synthesized compounds showed inhibitory activity at low nanomolar levels against hCA I, II, IX and XII, with selectivity against hCA II isoform, as well as hCA IX and XII isoforms. Docking studies were conducted to understand the activity and selectivity of the most potent and selective hydrazones towards different CA isoforms.
Article
Biochemistry & Molecular Biology
Chiara Testa, Anna Maria Papini, Reinhard Zeidler, Daniela Vullo, Fabrizio Carta, Claudiu T. Supuran, Paolo Rovero
Summary: This study reports the first Antibody-Drug-Conjugates (ADCs) containing human Carbonic Anhydrase (CA) directed Monoclonal Antibodies (MAbs) linked to low molecular weight inhibitors. The results show potent inhibition of tumor-associated CA enzymes and off-target human CA isoforms. These findings support the development of a novel class of ADCs for the treatment of chronic diseases such as cancer and inflammation.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Mostafa M. Ghorab, Aiten M. Soliman, Silvia Bua, Claudiu T. Supuran
Summary: A library of iodoquinazolinones with benzenesulfonamide moiety was synthesized as hCA inhibitors, among which compounds 12 and 15 showed high activity and selectivity against tumor-specific isoforms.
BIOORGANIC CHEMISTRY
(2021)
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
Chemistry, Medicinal
Pavitra S. Thacker, Vaishnavi Newaskar, Andrea Angeli, Dilep Kumar Sigalapalli, Nerella Sridhar Goud, Hepsibha Chirra, Afzal B. Shaik, Mohammed Arifuddin, Claudiu T. Supuran
Summary: A series of coumarin-linked thiazoles were synthesized and evaluated for their selective inhibition against human carbonic anhydrases IX and XII, which have been implicated in cancer. Compound 6o showed the best inhibition of hCA XII and can serve as a template for the design of other potent inhibitors.
ARCHIV DER PHARMAZIE
(2022)
Review
Immunology
Wenping Gong, Seppo Parkkila, Xueqiong Wu, Ashok Aspatwar
Summary: The ongoing COVID-19 pandemic caused by SARS-CoV-2 has become a global threat, with the emergence of several variants posing challenges to control efforts. Safe and effective vaccines against current and future variants are crucial for pandemic control. Coordinated surveillance, rapid vaccine redesign, and extensive vaccination are needed to counter the current and prevent future variants.
INTERNATIONAL REVIEWS OF IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ashok Aspatwar, Alessandro Bonardi, Heidi Aisala, Ksenia Zueva, Craig R. Primmer, Jaakko Lumme, Seppo Parkkila, Claudiu T. Supuran
Summary: The inhibitory effects of a beta-class carbonic anhydrase (CA) from the fish parasite Gyrodactylus salaris were investigated. Several effective inhibitors were identified, including simple heterocyclic sulphonamides and clinically used agents. This preliminary investigation provides insights into the inhibition profile of the parasite enzyme and potential development of more effective and selective inhibitors.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Review
Neurosciences
Ashok Aspatwar, Claudiu T. Supuran, Abdul Waheed, William S. Sly, Seppo Parkkila
Summary: Carbonic anhydrase V (CA V) is a mitochondrial enzyme that is highly expressed in the liver, while CA VB shows a broad tissue distribution. CA VA plays a predominant role in ammonia detoxification, and CA VB's roles in ureagenesis and gluconeogenesis are evident in the absence of CA VA. Early identification of CA VA deficiency can help prevent neurological sequelae.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Clinical Neurology
Antonios Thanellas, Heikki Peura, Mikko Lavinto, Tomi Ruokola, Moira Vieli, Victor E. Staartjes, Sebastian Winklhofer, Carlo Serra, Luca Regli, Miikka Korja
Summary: This study trained a deep learning algorithm to identify and localize subarachnoid hemorrhage (SAH) on head CT scans. The algorithm performed well in external validation and real-world testing, demonstrating high sensitivity and specificity for SAH detection.
Article
Oncology
Miriam Zatovicova, Ivana Kajanova, Martina Takacova, Lenka Jelenska, Olga Sedlakova, Martina Labudova, Silvia Pastorekova
Summary: Carbonic anhydrase IX (CA IX) is an enzyme involved in tumor adaptation to low oxygen levels and acidic environments. This study shows for the first time that CA IX can be shed by ADAM10 in addition to ADAM17. ADAM10 acts non-redundantly to ADAM17 in cleaving the extracellular domain of CA IX.
Article
Oncology
Katja Eloranta, Marjut Pihlajoki, Emmi Liljestroem, Ruth Nousiainen, Tea Soini, Jouko Lohi, Stefano Cairo, David B. Wilson, Seppo Parkkila, Markku Heikinheimo
Summary: Hypoxia induces the expression of CAIX in hepatoblastoma (HB) cells, and the CAIX inhibitor SLC-0111 shows in vitro activity against these malignant cells by decreasing cell viability and motility.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Miriam Hanckova, Lucia Mihalikova, Silvia Pastorekova, Tatiana Betakova
Summary: Macrophages in infected tissue are involved in the immune response and can be influenced by hypoxia. In this study, it was found that hypoxia inhibits macrophage proliferation, downregulates the RIG-I-like receptor signalling pathway, and affects the expression of cytokines and pro-inflammatory factors.
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
Morteza Abdoli, Alessandro Bonardi, Niccolo Paoletti, Ashok Aspatwar, Seppo Parkkila, Paola Gratteri, Claudiu T. Supuran, Raivis Zalubovskis
Summary: A library of structurally diverse N-((4-sulfamoylphenyl)carbamothioyl) amides was synthesized by selectively acylating 4-thioureidobenzenesulfonamide with various acyl chlorides. The inhibitory effects of these sulfonamides on human carbonic anhydrase (hCA) and bacterial beta-carbonic anhydrase from Mycobacterium tuberculosis (MtCA) were investigated in vitro and in silico. The compounds showed better inhibition against hCA I, hCA II, hCA VII, as well as MtCA1 and MtCA2, but poor inhibition against MtCA3.
Article
Medicine, General & Internal
Michael Veldeman, Tobias Rossmann, Miriam Weiss, Catharina Conzen-Dilger, Miikka Korja, Anke Hoellig, Jyri J. Virta, Jarno Satopaa, Teemu Luostarinen, Hans Clusmann, Mika Niemela, Rahul Raj
Summary: This study aimed to evaluate the effects of direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA) on patients with aneurysmal subarachnoid hemorrhage (SAH). The results showed that there were no significant differences in the severity and clinical outcome of SAH between patients who received DOAC or VKA treatment and their respective control groups.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biology
Mohammad Sadegh Gheibzadeh, Colleen Varaidzo Manyumwa, Oezlem Tastan Bishop, Hossein Shahbani Zahiri, Seppo Parkkila, Reza Zolfaghari Emameh
Summary: Hydrothermal vents are regions on the seafloor that contain fluids with highly enriched carbon dioxide and support a wide range of extremophile organisms. Carbonic anhydrases (CAs) are important enzymes for pH homeostasis and cellular functions, and their coding genes can be transferred between organisms via horizontal gene transfer (HGT). This study focuses on the alpha, beta, and gamma CAs from hydrothermal vent microbiomes and provides evidence of HGT of these genes between different species, suggesting the importance of CA enzymes for survival in these extreme environments and the conservation of natural diversity.
Article
Infectious Diseases
Susanna Haapanen, Maarit S. Patrikainen, Seppo Parkkila
Summary: Acanthamoeba keratitis is a severe infectious disease of the cornea caused by an opportunistic amoeba, Acanthamoeba castellanii. The diagnosis is often delayed, resulting in irreversible damage to vision. We have developed PCR-based methods that can detect A. castellanii in less than 3 hours with high sensitivity, allowing for timely treatment to prevent long-term complications.
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
(2023)
Article
Nutrition & Dietetics
Juho Luoma, Laura Adubra, Per Ashorn, Ulla Ashorn, Jaden Bendabenda, Kathryn G. Dewey, Lotta Hallamaa, Ryan Coghlan, William A. Horton, Heikki Hyoty, Emma Kortekangas, Kirsi-Maarit Lehto, Kenneth Maleta, Andrew Matchado, Minyanga Nkhoma, Sami Oikarinen, Seppo Parkkila, Sami Purmonen, Yue-Mei Fan
Summary: Inadequate diet and frequent symptomatic infections are major causes of growth stunting in low-income countries. However, interventions targeting these risk factors have achieved limited success. Asymptomatic infections, which are prevalent among children, may also contribute to growth stunting indirectly through increased systemic inflammation and reduced plasma insulin-like growth factor 1 (IGF-1) concentration.
MATERNAL AND CHILD NUTRITION
(2023)
Article
Clinical Neurology
Jasper Hans van Lieshout, Bastian Malzkorn, Hans-Jakob Steiger, Cihat Karadag, Marcel A. Kamp, Peter Vajkoczy, Juergen Beck, Simone Peschillo, Veit Rohde, Daniel Walsh, Vasiliy Lukshin, Miikka Korja, Marco Cenzato, Andreas Raabe, Andreas Gruber, Daniel Haenggi, H. D. Boogaarts
Summary: Through team meetings and expert opinions, seven core procedural entrustable professional activities (EPAs) for vascular neurosurgical training were identified, including non-complex aneurysm surgery, complex aneurysm surgery, bypass surgery, arteriovenous malformation resection, spinal dural fistula surgery, perioperative management, and clinical decision-making.
ACTA NEUROCHIRURGICA
(2023)
Review
Clinical Neurology
Joonas Laajava, Miikka Korja
Summary: The prevalence and persistence of edematous changes after meningioma surgery is limited. Peritumoral edema often presents as irreversible gliosis, which may affect long-term postoperative epilepsy. A systematic literature search was conducted, and seven studies met inclusion criteria. Persistent edema rates ranged from 39% to 83%, with assessment earliest at one year post-surgery. Reliable evaluation of T2/FLAIR hyperintensity changes can be made at this time. Future studies are needed to explore the etiology, persistence, and impact of peritumoral meningioma-related edema on postoperative epilepsy.
NEUROSURGICAL REVIEW
(2023)