This manuscript reports the identification of a novel series of mono- and bis- benzene sulfonamides with potent binding affinity for bovine carbonic anhydrase II (bCAII). These compounds exhibited nanomolar equilibrium dissociation constants with K(i)'s ranging from 4.7 to 9.3nM. All compounds were ester derivatives of the weak affinity bCAII inhibitor, 4-carboxybenzenesulfonamide. Structure-activity relationships for this novel series of compounds are discussed.
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http://dx.doi.org/10.1016/j.bmcl.2005.08.113 | DOI Listing |
Phys Chem Chem Phys
January 2025
School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia QLD 4072, Australia.
Steroids are organic compounds found in all forms of biological life. Besides their structural roles in cell membranes, steroids act as signalling molecules in various physiological processes and are used to treat inflammatory conditions. It has been hypothesised that in addition to their well-characterised genomic and non-genomic pathways, steroids exert their biological or pharmacological activities an indirect, nonreceptor-mediated membrane mechanism caused by steroid-induced changes to the physicochemical properties of cell membranes.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Department of Orthodontics, State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Neprilysin (NEP), a zinc-dependent membrane-bound metallopeptidase, regulates various bioactive peptides, particularly in kidneys, vascular endothelium, and the central nervous system. NEP's involvement in metabolizing natriuretic peptides, insulin, and enkephalins makes it a promising target for treating cardiovascular and Alzheimer's diseases. Several NEP inhibitors, such as sacubitril and omapatrilat, have been approved for clinical use, which inhibit NEP activity to prolong the bioactivity of beneficial peptides, thereby exerting therapeutic effects.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
Section of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Sesto Fiorentino, Firenze, Italy.
2,2'-Thio-bis(4,6-dichlorophenol), namely bithionol, is a small molecule endowed with a multifaceted bioactivity. Its peculiar polychlorinated phenolic structure makes it a suitable candidate to explore its potentialities in establishing interaction patterns with enzymes of MedChem interest, such as the human carbonic anhydrase (hCA) metalloenzymes. Herein, bithionol was tested on a panel of specific hCAs through the stopped-flow technique, showing a promising micromolar inhibitory activity for the hCA II isoform.
View Article and Find Full Text PDFNat Commun
January 2025
University of Pittsburgh, Department of Computer Science, Pittsburgh, PA, 15260, USA.
Reliable molecular property prediction is essential for various scientific endeavors and industrial applications, such as drug discovery. However, the data scarcity, combined with the highly non-linear causal relationships between physicochemical and biological properties and conventional molecular featurization schemes, complicates the development of robust molecular machine learning models. Self-supervised learning (SSL) has emerged as a popular solution, utilizing large-scale, unannotated molecular data to learn a foundational representation of chemical space that might be advantageous for downstream tasks.
View Article and Find Full Text PDFPhytochemistry
January 2025
School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, P.R. China; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou 450046, P. R. China; Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan Province and Ministry of Education of China. Zhengzhou 450046, P.R. China. Electronic address:
From the tuber of Alisma orientale (Sam.) Juzep. (Alismataceae), twenty-four compounds were isolated, including six (1, 2, 3, 10, 14, and 17) that were not yet characterized.
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