X-ray crystal structures of the adducts of human carbonic anhydrase (hCA) isozyme II with derivatives incorporating a sulfamide or sulfamic acid moiety are reported. The absence of a C-SO(2)NH(2) bond in the first type of compound can be exploited for the design of more potent and selective CA inhibitors. This study also explains why sulfate is a several-orders-of-magnitude weaker CA inhibitor compared to derivatives incorporating sulfonamide/sulfamide moieties.
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http://dx.doi.org/10.1021/jm011131t | DOI Listing |
J Clin Med
December 2024
Department of Adult Critical Care, Guy's and St Thomas' NHS Foundation Trust, King's Health Partners, London SE1 9RT, UK.
Extracorporeal carbon dioxide removal (ECCOR) is an emerging technique designed to reduce carbon dioxide (CO) levels in venous blood while enabling lung-protective ventilation or alleviating the work of breathing. Unlike high-flow extracorporeal membrane oxygenation (ECMO), ECCOR operates at lower blood flows (0.4-1.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Neurofarba Department, Section of Pharmaceutical Sciences, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
, the causative agent of toxoplasmosis, is a protozoan parasite capable of infecting a wide range of hosts, posing significant health risks, particularly to immunocompromised individuals and congenital transmission. Current therapeutic options primarily target the active tachyzoite stage but are limited by issues such as toxicity and incomplete efficacy. As a result, there is an urgent need for alternative therapies that can selectively target parasite-specific mechanisms critical for metabolic processes and host-parasite interactions.
View Article and Find Full Text PDFJ Med Chem
January 2025
Sezione di Scienze Farmaceutiche, NeuroFarba Department, Universita degli Studi di Firenze, Via Ugo Schiff 6, Sesto Fiorentino 50019, Italy.
Novel 3-sulfonamide pyrrol-2-one derivatives containing two sulfonamide groups were synthesized via a one-pot, three-component method using trifluoroacetic acid as a catalyst. Structural confirmation was achieved using spectroscopic techniques. The compounds were tested against four selected human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX, and hCA XII).
View Article and Find Full Text PDFBioorg Chem
January 2025
Institute of Chemical Sciences, Bahauddin Zakariya University, 60800 Multan, Pakistan. Electronic address:
A series of novel phenyl naphthalene-2-sulfonate-based thiosemicarbazones (5a-v) were synthesized and evaluated for their inhibitory activity against human carbonic anhydrases I and II (hCA I and hCA II). Compounds 5d and 5p demonstrated the highest inhibitory potency, with IC values of 4.32 ± 0.
View Article and Find Full Text PDFCommun Biol
January 2025
Obsidian Therapeutics, Cambridge, MA, USA.
Adoptive cell therapies (ACT) have shown reduced efficacy against solid tumor malignancies compared to hematologic malignancies, partly due to the immunosuppressive nature of the tumor microenvironment (TME). ACT efficacy may be enhanced with pleiotropic cytokines that remodel the TME; however, their expression needs to be tightly controlled to avoid systemic toxicities. Here we show T cells can be armored with membrane-bound cytokines with surface expression regulated using drug-responsive domains (DRDs) developed from the 260-amino acid protein human carbonic anhydrase 2 (CA2).
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