Design, synthesis and biological evaluation of novel 1,2,3-triazolyl β-hydroxy alkyl/carbazole hybrid molecules.
The design, synthesis and biological study of several novel 1,2,3-triazolyl [Formula: see text]-hydroxy alkyl/carbazole hybrid molecules as a new type of antifungal agent has been described. In this synthesis, the N-alkylation reaction of carbazol-9-ide potassium salt with 3-bromoprop-1-yne afforded 9-(prop-2-ynyl)-9H-carbazole. The 'Click' Huisgen cycloaddition reaction of 9-(prop-2-ynyl)-9H-carbazole with diverse [Formula: see text]-azido alcohols in the presence of copper-doped silica cuprous sulphate led to target molecules in excellent yields. The in vitro antifungal and antibacterial activities of title compounds were screened against various pathogenic fungal strains, Gram-positive and/or Gram-negative bacteria. In particular, 1-(4-((9H-carbazol-9-yl) methyl)-1H-1,2,3-triazol-1-yl)-3-butoxypropan-2-ol (10e) proved to have potent antifungal activity against all fungal tests compared with fluconazole and clotrimazole as studied reference drugs. Our molecular docking analysis revealed an appropriate fitting and a potential powerful interaction between compound 10e and an active site of the Mycobacterium P450DM enzyme. The strong hydrogen bondings between [Formula: see text]-hydroxyl and ether groups in 10e were found to be the main factors that drive the molecule to fit in the active site of enzyme. The in silico pharmacokinetic studies were used for a better description of 10a-10n as potential lead antifungal agents for future investigations.
Department of Chemistry, Shiraz University of Technology, 71555-313, Shiraz, Iran. soltani@sutech.ac.ir.
Mohammad Navid Soltani
MN
Rad
Department of Chemistry, Shiraz University of Technology, 71555-313, Shiraz, Iran. behrouz@sutech.ac.ir.
Somayeh
S
Behrouz
Department of Chemistry, Shiraz University of Technology, 71555-313, Shiraz, Iran.
Marzieh
M
Behrouz
Department of Chemistry, Shiraz University of Technology, 71555-313, Shiraz, Iran.
Akram
A
Sami
Fasa University of Medical Sciences, Fasa, Iran.
Mehdi
M
Mardkhoshnood
Fasa University of Medical Sciences, Fasa, Iran.
Ali
A
Zarenezhad
Fasa University of Medical Sciences, Fasa, Iran.
Elham
E
Zarenezhad
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D057930:Click Chemistry; D061565:Cycloaddition Reaction; D015195:Drug Design; D006860:Hydrogen Bonding; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002227:Carbazoles
-Hydroxy 1, 2, 3-triazole; Antibacterial; Antifungal; Carbazole; Mycobacterium P450DM