Microwave Optimized Synthesis of N-(adamantan-1-yl)-4-[(adamantan-1-yl)-sulfamoyl]benzamide and Its Derivatives for Anti-Dengue Virus Activity
| Autor: | Eugene B Foxen, Jacques Joubert, Sarel F. Malan |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
anti-dengue virus serotype 2 activity Pharmaceutical Science Dengue virus medicine.disease_cause 01 natural sciences Medicinal chemistry Analytical Chemistry lcsh:QD241-441 03 medical and health sciences chemistry.chemical_compound lcsh:Organic chemistry sulfonamide Drug Discovery medicine Acyl halide Physical and Theoretical Chemistry Cytotoxicity Benzamide microwave irradiation Benzoic acid Substitution reaction amantadine Nucleophilic addition 010405 organic chemistry Organic Chemistry 0104 chemical sciences 030104 developmental biology chemistry Chemistry (miscellaneous) Docking (molecular) docking cytotoxicity Molecular Medicine |
| Zdroj: | Molecules, Vol 23, Iss 7, p 1678 (2018) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules23071678 |
| Popis: | Dengue fever is a major public health concern in many tropical and sub-tropical regions. The development of agents that are able to inhibit the dengue virus (DENV) is therefore of utmost importance. This study focused on the synthesis of dual acting hybrids comprising structural features of known DENV inhibitors, amantadine (1) and benzsulfonamide derivatives. Hybrid compound 3, N-(adamantan-1-yl)-4-[(adamantan-1-yl)sulfamoyl]benzamide, was synthesized by reacting amantadine (1) with 4-(chlorosulfonyl)benzoic acid (2), after optimization, in a 2:1 ratio under microwave irradiation conditions in a one-pot reaction. Mono-adamantane derivatives 6 and 7 were synthesised via acyl halide formation of benzoic acid (4) and 4-sulfamoyl benzoic acid (5), respectively, followed by conjugation with amantadine (1) through a conventional or microwave irradiation assisted nucleophilic addition/substitution reaction. The use of microwave irradiation lead to significant increases in yields and a reduction in reaction times. Nuclear magnetic resonance, infra-red and mass spectral data confirmed the structures. Compound 3 and 7 showed significant anti-DENV serotype 2 activity (IC50 = 22.2 µM and 42.8 µM) and low cytotoxicity (CC50 < 100 µM). Possible mechanisms of action are also proposed, which are based on the biological results and molecular docking studies. |
| Databáze: | OpenAIRE |
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