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Novel 1,3,5-Triazinyl Aminobenzenesulfonamides Incorporating Aminoalcohol, Aminochalcone and Aminostilbene Structural Motifs as Potent Anti-VRE Agents, and Carbonic Anhydrases I, II, VII, IX, and XII Inhibitors
- Source :
- International Journal of Molecular Sciences, Vol 23, Iss 231, p 231 (2022), International Journal of Molecular Sciences, International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 231
- Publication Year :
- 2022
- Publisher :
- MDPI AG, 2022.
-
Abstract
- A series of 1,3,5-triazinyl aminobenzenesulfonamides substituted by aminoalcohol, aminostilbene, and aminochalcone structural motifs was synthesized as potential human carbonic anhydrase (hCA) inhibitors. The compounds were evaluated on their inhibition of tumor-associated hCA IX and hCA XII, hCA VII isoenzyme present in the brain, and physiologically important hCA I and hCA II. While the test compounds had only a negligible effect on physiologically important isoenzymes, many of the studied compounds significantly affected the hCA IX isoenzyme. Several compounds showed activity against hCA XII; (E)-4-{2-[(4-[(2,3-dihydroxypropyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (31) and (E)-4-{2-[(4-[(4-hydroxyphenyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (32) were the most effective inhibitors with KIs = 4.4 and 5.9 nM, respectively. In addition, the compounds were tested against vancomycin-resistant Enterococcus faecalis (VRE) isolates. (E)-4-[2-({4-[(4-cinnamoylphenyl)amino]-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)ethyl]benzenesulfonamide (21) (MIC = 26.33 µM) and derivative 32 (MIC range 13.80–55.20 µM) demonstrated the highest activity against all tested strains. The most active compounds were evaluated for their cytotoxicity against the Human Colorectal Tumor Cell Line (HCT116 p53 +/+). Only 4,4’-[(6-chloro-1,3,5-triazin-2,4-diyl)bis(iminomethylene)]dibenzenesulfonamide (7) and compound 32 demonstrated an IC50 of ca. 6.5 μM; otherwise, the other selected derivatives did not show toxicity at concentrations up to 50 µM. The molecular modeling and docking of active compounds into various hCA isoenzymes, including bacterial carbonic anhydrase, specifically α-CA present in VRE, was performed to try to outline a possible mechanism of selective anti-VRE activity.
- Subjects :
- Carbonic Anhydrase I
QH301-705.5
carbonic anhydrase
chalcone
Antineoplastic Agents
Molecular Dynamics Simulation
Carbonic Anhydrase II
Catalysis
Article
Inorganic Chemistry
Structure-Activity Relationship
Neoplasms
Humans
Physical and Theoretical Chemistry
Biology (General)
Carbonic Anhydrase IX
Carbonic Anhydrase Inhibitors
Molecular Biology
QD1-999
Spectroscopy
Carbonic Anhydrases
Sulfonamides
Organic Chemistry
General Medicine
HCT116 Cells
vancomycin-resistant enterococci
inhibition
Computer Science Applications
Anti-Bacterial Agents
benzenesulfonamide
Molecular Docking Simulation
stilbene
Chemistry
triazine
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Volume :
- 23
- Issue :
- 231
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....f94d142e1284716e7d58e5015931506d