Article
Biochemistry & Molecular Biology
Francesca Mancuso, Anna Di Fiore, Laura De Luca, Andrea Angeli, Giuseppina De Simone, Claudiu T. Supuran, Rosaria Gitto
Summary: To address the challenge of isoform selectivity, the entrance of the cavity for certain druggable human Carbonic Anhydrases (hCAs) was explored. Using X-ray crystallographic studies, a series of 4-(4(hetero)aroylpiperazine-1-carbonyl)benzene-1-sulfonamides was developed based on complex with hCA VII. Through docking simulations, the capability of newer benzenesulfonamides to fit the hCA VII catalytic cavity was evaluated. Subsequently, a series of thirteen benzenesulfonamides was synthesized and tested, with the 4-(4-(furan-2-carbonyl)piperazine-1-carbonyl)benzenesulfonamide showing significant affinity towards hCA VII and good selectivity over hCA I when compared to Topiramate (TPM).
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Anil Kumar Marapaka, Alessio Nocentini, Molly S. Youse, Weiwei An, Katrina J. Holly, Chittaranjan Das, Ravi Yadav, Mohamed N. Seleem, Claudiu T. Supuran, Daniel P. Flaherty
Summary: Drug-resistant Neisseria gonorrhoeae poses a serious threat to public health. The research team solved the structure of carbonic anhydrase inhibitors bound to the essential alpha-carbonic anhydrase isoform from N. gonorrhoeae, revealing differences compared to the human enzyme.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Arzu Gumus, Murat Bozdag, Andrea Angeli, Thomas S. Peat, Fabrizio Carta, Claudiu T. Supuran, Silvia Selleri
Summary: In this study, a small series of compounds with inhibitory properties for human Carbonic Anhydrase enzymes were reported for the first time. Some of these compounds showed good selectivity for specific CAs, and one compound exhibited nearly matching K-I values for both hCA II and IX. X-ray crystal experiments were used to explore the binding mode of this compound within the CA IX mimic isoform.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
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
Chemistry, Medicinal
Andrea Angeli, Marta Ferraroni, Antonella Capperucci, Damiano Tanini, Gabriele Costantino, Claudiu T. Supuran
Summary: This study presents the activity of selenocarbamates as novel carbonic anhydrase (CA) inhibitors. Through CA-mediated hydrolysis, selenocarbamates release selenolates that effectively inhibit CA by binding to zinc. Different human CA isoforms were evaluated against a series of selenocarbamates with high molecular diversity and complexity. X-ray studies provided insights into the binding mode of this novel class of CA inhibitors.
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
Biochemistry & Molecular Biology
Andrea Angeli, Marta Ferraroni, Alessandro Bonardi, Claudiu T. Supuran, Alessio Nocentini
Summary: Carbonic anhydrases (CAs) are important zinc metalloenzymes that catalyze the hydration of carbon dioxide. They play crucial roles in various biological processes and can be targeted for the treatment of diseases like glaucoma, obesity, and cancer. In this study, we report the co-crystallization of a N-nitro sulphonamide derivative with human CA II, revealing the binding site and mode of inhibition. This knowledge could aid in the development of more potent and selective CA inhibitors.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Atteeque Ahmed, Aftab Ahmed, Pervaiz Ali Channar, Syeda Abida Ejaz, Aisha A. Alsfouk, Aamer Saeed, Rabail Ujan, Qamar Abbas, Tuncer Hokelek, Michael Bolte
Summary: Carbonic anhydrases (CAs) are widely expressed metalloenzymes that play a crucial role in various physiological and pathological processes. An alkyl substituted acyl thiourea compound was synthesized and characterized using NMR spectroscopy and single crystal X-ray diffraction. The synthesized compound showed hydrogen bonding and H···H interactions, and demonstrated inhibition of carbonic anhydrase activity. Quantum mechanical descriptors, molecular docking, and ADMET analysis were performed to analyze the compound's properties and potential as a drug inhibitor of carbonic anhydrase.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Alessandro Bonardi, Silvia Bua, Jacob Combs, Carrie Lomelino, Jacob Andring, Sameh Mohamed Osman, Alessandra Toti, Lorenzo Di Cesare Mannelli, Paola Gratteri, Carla Ghelardini, Robert McKenna, Alessio Nocentini, Claudiu T. Supuran
Summary: Human carbonic anhydrase isoforms IX and XII have been confirmed as anticancer targets, with three-tails approach showing higher selectivity against tumor-associated isoforms and demonstrating anti-proliferative effects in various cancer cell lines. X-ray crystallography studies have been conducted to investigate the binding mode of these inhibitors, providing valuable insights for potential cancer treatments.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Biology
Emma Langella, Davide Esposito, Simona Maria Monti, Claudiu T. Supuran, Giuseppina De Simone, Vincenzo Alterio
Summary: Carbonic anhydrases are enzymes involved in an important physiological reaction of converting CO2 to bicarbonate ion. They play crucial roles in various physiological and pathological processes in humans, making them potential targets for therapeutic interventions. This study investigates a class of carbonic anhydrase inhibitors, providing insights into their mechanism of action and potential for drug design.
Article
Chemistry, Medicinal
Murat Bozdag, Lochlin Cravey, Jacob Combs, Anusha Kota, Robert McKenna, Andrea Angeli, Silvia Selleri, Fabrizio Carta, Claudiu T. Supuran
Summary: This study reports on the aryl sulfonamide inhibitors of human carbonic anhydrase enzymes and their inhibitory potency against different isoforms. Through X-ray crystallography analysis, the study reveals the critical interactions between the inhibitors and different isoforms. This research has implications for developing highly selective hCA inhibitors.
Article
Biochemistry & Molecular Biology
Qingjie Xiao, Ting Xue, Wen Shuai, Chengyong Wu, Zhixiong Zhang, Ting Zhang, Shaoxue Zeng, Bo Sun, Yuxi Wang
Summary: Crystal structures of three taxane-site inhibitors, Ixabepilone, Epothilone B, and Epothilone D, were reported, showing similar binding modes to promote tubulin polymerization. Through virtual screening, novel taxane-site inhibitors with simpler chemical structures were identified, and derivatives with higher binding affinity to tubulin were designed and developed.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
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)
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
Virology
Nikita Zrelovs, Kristaps Lamsters, Janis Karuss, Maris Krievans, Andris Dislers, Andris Kazaks
Article
Multidisciplinary Sciences
Elina Cernooka, Janis Rumnieks, Nikita Zrelovs, Kaspars Tars, Andris Kazaks
Summary: Endolysins are enzymes encoded by bacteriophages that have the potential to treat multidrug-resistant bacterial infections. The study found that the endolysin encoded by Hafnia phage Enc34 has an unusual structure and exhibits activity against peptidoglycan from different bacteria. The research also reveals the evolutionary relationship between Enc34 endolysin and other enzymes at the molecular level.
SCIENTIFIC REPORTS
(2022)
Article
Biotechnology & Applied Microbiology
Emils Bolmanis, Oskars Grigs, Andris Kazaks, Vytautas Galvanauskas
Summary: This research investigated the production and purification of hepatitis B core antigen (HBcAg) under different levels of residual methanol. The results showed that high yields and purity of HBcAg could be achieved under limiting residual methanol concentration.
BIOPROCESS AND BIOSYSTEMS ENGINEERING
(2022)
Article
Microbiology
Nikita Zrelovs, Juris Jansons, Andris Dislers, Andris Kazaks
Summary: This study reports on the genomic characterization of an insect associated Morganella sp. phage, Mecenats66, isolated from dead worker honeybees. The phage was found to employ a headful packaging strategy with a preferred packaging initiation site, representing an evolutionarily distinct subtype. These findings could aid in predicting packaging strategies of newly isolated phages in the future.
Article
Biochemistry & Molecular Biology
Nikita Zrelovs, Juris Jansons, Tatjana Kazaka, Andris Kazaks, Andris Dislers
Summary: Pantoea spp. found in various environmental sources can benefit or harm plants, and some species are known human pathogens. This study isolated a strain of P. agglomerans from a dead Latvian grasshopper, and used it to retrieve three different lytic phages, including one with unusual morphology. Genome sequencing confirmed their characteristics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jekaterina Ivanova, Morteza Abdoli, Alessio Nocentini, Raivis Zalubovskis, Claudiu T. Supuran
Summary: A series of 4-methyl-1,2,3-benzoxathiazine-2,2-dioxides with different substituents were synthesized. The compounds showed nanomolar inhibitory effects on target hCA IX and XII, while exhibiting low or no inhibitory properties on off-target hCA I and moderate inhibition on hCA II. The derivatives of 4-methyl-1,2,3-benzoxathiazine 2,2-dioxide demonstrated excellent selectivity towards CA IX/XII over hCA I and very good selectivity towards CA IX/XII over hCA II.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jekaterina Ivanova, Morteza Abdoli, Alessio Nocentini, Raivis Zalubovskis, Claudiu T. Supuran
Summary: A series of 1,2,3-benzoxathiazine-2,2-dioxides with various substituents were synthesized and their inhibitory activity on carbonic anhydrase isoforms was investigated. Some of the derivatives showed promising selectivity towards specific isoforms.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Jekaterina Ivanova, Alessio Nocentini, Kaspars Tars, Janis Leitans, Elviss Dvinskis, Andris Kazaks, Ilona Domraceva, Claudiu T. Supuran, Raivis Zalubovskis
Summary: In this study, we present a series of sulfonamide derivatives with flexible moieties that can adapt their geometry in the active center of enzymes, resulting in effective and selective inhibition of carbonic anhydrase enzymes. These compounds demonstrated potent in vitro inhibition activity against cancer-related hCA isoforms and exhibited cytotoxic effects on cancer cell lines. Crystallographic experiments confirmed the binding modes of compound 35 with the active centers of hCA IX and hCA XII.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Gints Kalnins, Maris Bertins, Arturs Viksna, Kaspars Tars
Summary: In this study, the functionalization of bacterial microcompartment (BMC) shell lumens was demonstrated to significantly increase the loading capacity of iron and cobalt. This suggests the possibility of passive flow of cobalt and iron atoms across the BMC shell.
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
Biochemistry & Molecular Biology
Anna Nikitjuka, Kristaps Krims-Davis, Iveta Kanepe-Lapsa, Melita Ozola, Raivis Zalubovskis
Summary: Thioredoxin reductase is crucial for maintaining cellular redox homeostasis and its overexpression is associated with cancer development. Compounds containing Michael acceptor functionality show higher inhibitory effects against thioredoxin reductase.
Review
Chemistry, Multidisciplinary
Dan He, Yawen Li, Fuwen Zhao, Yuze Lin
Summary: High trap density in organic solar cells leads to localized charge carriers and reduced carrier lifetime, limiting device efficiency. This feature article summarizes the recent advances of trap suppression by material design and device engineering.
CHEMICAL COMMUNICATIONS
(2024)
Review
Chemistry, Multidisciplinary
Olivier Monfort, Arshitha Madhusudhan, Martin Motola
Summary: This article presents the advantages of coupling photocatalysis and Fenton-based processes for environmental remediation and discusses their synergy. It critically examines the simultaneous triggering of these two processes and provides insights into research approaches. The study aims to enhance understanding of this complex process and highlight the potential integration of new catalysts in current wastewater treatment technology.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Manideepa Dhar, Chittaranjan Mishra, Avijit Das, Uttam Manna
Summary: An approach of 'polymerization of monomers in its aggregated form' has been introduced to tailor the water wettability of fibrous and porous substrates, achieving hydrophobicity to superhydrophobicity transition, as well as patterned wettability. This facile chemical method provides a durable coating with adjustable and patterned wettability for various potential applications.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Saswat Ranjan Bhoi, Chhanda Debnath, Shikha Gandhi
Summary: In this article, a novel catalytic reaction using Pd(0) and Bronsted acid is reported for the synthesis of biologically important imidazolidinone-fused N-heterocycles through redox-neutral intramolecular N-allylation of indoles and pyrroles with alkynes. This atom-economical method is applicable to a wide range of substrates and eliminates the need for leaving groups or oxidizing agents commonly used in traditional allylation reactions.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Longkun Chen, Mingshuai Zhang, Meichen Liu, Zhuoyuan Liu, Yuetong Qiu, Zhilai Zhang, Fuchao Yu, Jiuzhong Huang
Summary: In this study, an efficient Rh(III)-catalyzed selective mono- and dual-C-H bond functionalization/cyclization with iodonium ylide as the sole coupling partner was demonstrated. Fused benzodiazepine skeletons were obtained in excellent yields, providing an improved approach to dual C-H unsymmetrical functionalization.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Alice Kennett, Sven Epple, Gabriella van der Valk, Irene Georgiou, Evelyne Gout, Romain R. Vives, Angela J. Russell
Summary: This study presents the design and synthesis of sulfated disaccharide inhibitors based on IdoA(2S)-GlcNS(6S), which showed potent inhibition of Sulf-2. The results suggest that IdoA(2S)-GlcNS(6S) is the shortest fragment size required for effective inhibition of Sulfs, and a trisulfated disaccharide is identified as the minimal fragment size of heparan sulfate for effective endosulfatase inhibition.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Mauro Garbini, Andrea Brunetti, Riccardo Pedrazzani, Magda Monari, Massimo Marcaccio, Giulio Bertuzzi, Marco Bandini
Summary: The self-adaptability of galvanostatic electrolysis was found to be helpful in a multistage chemo- and diastereoselective electrochemically promoted cyclodimerization of chalcones. Through a series of reductive events, densely functionalized cyclopentanes with five contiguous stereocenters were obtained (25 examples, yields up to 95%, dr values up to >20:1). Further experimental and electrochemical investigations indicated the crucial role of dynamic kinetic resolution of the aldol intermediate in the reaction mechanism.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Dhananjay S. Nipate, Neha Meena, Prakash N. Swami, Krishnan Rangan, Anil Kumar
Summary: In this study, the synthesis of functionalized benzo[a]phenazines and indazolo[2,3-a]quinolines was achieved through Rh(III)-catalyzed oxidative annulation of 2-arylquinoxalines and 2-aryl-2H-indazoles with allyl alcohols. The method showed a wide substrate scope, excellent functional group tolerance, good to high yields of annulated products, and the capability for scaled-up synthesis. A tentative mechanism of the annulation reaction was proposed based on a preliminary mechanistic investigation.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Ruonan Zhang, Abudukadi Tudi, Xia Yang, Xuping Wang, Zhihua Yang, Shujuan Han, Shilie Pan
Summary: A new lead tellurium borate material with a unique fundamental building block [B4O10] was synthesized and found to exhibit high birefringence. The structure-property relationship was discussed using first-principles calculations.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Amresh Kumar Singh, Baishali Thakurta, Anupam Giri, Monalisa Pal
Summary: This study introduces three key concepts for the quick synthesis of large-scale high-quality 2D materials films and their utilization in device fabrication.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Reina Hagiwara, Shun Nishimura, Kosuke Okeyoshi
Summary: A copolymer-conjugated nanocatalytic system has been developed to improve electron transfer and enhance photoinduced H2 generation.
CHEMICAL COMMUNICATIONS
(2024)
