Design and synthesis of new N-(5-trifluoromethyl)-1H-1,2,4-triazol-3-yl benzenesulfonamides as possible antimalarial prototypes

• Published in: Molecules (Basel, Switzerland) Vol. 16; no. 9; pp. 8083 - 8097
• Main Authors: Boechat, Nubia, Pinheiro, Luiz C S, Santos-Filho, Osvaldo A, Silva, Isabor C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.09.2011; MDPI
• Subjects: Amino Acid Sequence; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antiparasitic agents; Benzenesulfonamides; Biological activity; Catalytic Domain; Chemistry; Computer Simulation; Conserved Sequence; Cyclization; Design; DHPS; Dihydrofolate reductase; dihydropteroate synthase; Dihydropteroate Synthase - chemistry; Drug Design; Drugs; Enzymes; Fluorine Compounds - chemical synthesis; Fluorine Compounds - chemistry; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Malaria; Models, Molecular; Molecular Sequence Data; Molecular Structure; Parasites; Pharmaceutical sciences; Plasmodium falciparum - enzymology; Protein Binding; Sulfadiazine - chemistry; Sulfadoxine - chemistry; Sulfalene - chemistry; sulfonamide; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Thermodynamics; Triazoles - chemical synthesis; Triazoles - chemistry; trifluoromethyl; Tropical diseases; Africa
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules16098083

A rational approach was used to synthesize a new set of 15 1H-1,2,4-triazol-3-yl benzenesulfonamide derivatives with the aim of developing new antimalarial lead compounds. These derivatives were prepared in yields between 50% and 62%, and their structures were elucidated using IR, ¹H-, ¹³C-, ¹⁹F-NMR, MS and elemental analysis. A docking study based on sulfonamides previously used against malaria identified trifluoromethyl-substituted derivatives to be the best lead compounds for new antimalarial drug development.