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Keywords = claramine series

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19 pages, 4216 KB  
Article
Synthesis and QSAR Studies of Claramine Derivatives, a New Class of Broad-Spectrum Antimicrobial Agents
by Marine Blanchet, Carole Di Giorgio and Jean Michel Brunel
Molecules 2025, 30(23), 4614; https://doi.org/10.3390/molecules30234614 - 1 Dec 2025
Viewed by 319
Abstract
The development of new antibiotics has been recognized for over two decades as a major challenge in combating multidrug-resistant bacteria. Herein, we report the synthesis and QSAR studies of claramine derivatives, a new class of broad-spectrum antimicrobial agents active against both susceptible and [...] Read more.
The development of new antibiotics has been recognized for over two decades as a major challenge in combating multidrug-resistant bacteria. Herein, we report the synthesis and QSAR studies of claramine derivatives, a new class of broad-spectrum antimicrobial agents active against both susceptible and resistant Gram-positive and Gram-negative strains. The observed antimicrobial activities were rationalized based on key topological parameters of the derivatives, while cytotoxicity was interpreted by correlating half maximal inhibitory concentration (IC50) values with QSAR models. Owing to the low cytotoxicity observed for several analogues, this molecular class represents a promising alternative for the development of novel agents to counteract multidrug resistance. Full article
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21 pages, 2531 KB  
Article
Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies
by Ledy De-la-Cruz-Martínez, Constanza Duran-Becerra, Martin González-Andrade, José C. Páez-Franco, Juan Manuel Germán-Acacio, Julio Espinosa-Chávez, J. Martin Torres-Valencia, Jaime Pérez-Villanueva, Juan Francisco Palacios-Espinosa, Olivia Soria-Arteche and Francisco Cortés-Benítez
Molecules 2021, 26(14), 4375; https://doi.org/10.3390/molecules26144375 - 20 Jul 2021
Cited by 21 | Viewed by 5373
Abstract
Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B [...] Read more.
Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B inhibitors to date. Herein we describe the synthesis and evaluation of two series of indole- and N-phenylpyrazole-GA derivatives (4af and 5af). We measured their inhibitory activity and enzyme kinetics against PTP1B using p-nitrophenylphosphate (pNPP) assay. GA derivatives bearing substituted indoles or N-phenylpyrazoles fused to their A-ring showed a 50% inhibitory concentration for PTP1B in a range from 2.5 to 10.1 µM. The trifluoromethyl derivative of indole-GA (4f) exhibited non-competitive inhibition of PTP1B as well as higher potency (IC50 = 2.5 µM) than that of positive controls ursolic acid (IC50 = 5.6 µM), claramine (IC50 = 13.7 µM) and suramin (IC50 = 4.1 µM). Finally, docking and molecular dynamics simulations provided the theoretical basis for the favorable activity of the designed compounds. Full article
(This article belongs to the Special Issue Discovery of Enzyme Inhibitors from Natural Products)
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