Design, Synthesis and Antifungal Activity of New Schiff Bases Bearing 2-Aminothiophene Derivatives Obtained by Molecular Simplification

AUTOR(ES)

Luna, Isadora S.; Neves, Wendell W.; Lima-Neto, Reginaldo G. de; Albuquerque, Amanda P. B.; Pitta, Maíra G. R.; Rêgo, Moacyr J. B. M.; Neves, Rejane P.; Scotti, Marcus T.; Mendonça-Junior, Francisco J. B.

FONTE

J. Braz. Chem. Soc.

DATA DE PUBLICAÇÃO

2021-05

RESUMO

Seventeen Schiff bases bearing 2-aminothiophene derivatives were designed and synthesized using molecular simplification. The resulting compounds (4a-4q) were evaluated for their in vitro antifungal activity against dermatophytes. Prediction of their druglikeness and pharmacokinetic properties, establishment of their structure-activity relationships (SAR), and cytotoxic evaluation of the most active compounds were performed. Using an eco-friendly procedure, microwave assisted synthesis resulted in compounds in good yields (35-85%). Compounds 4a-4q presented good druglikeness and pharmacokinetic profiles and no cytotoxicity for any cell line tested up to 100 µM. The compounds presenting the best antifungal profiles were 4e, 4f, 4g, 4k, 4l, 4m, 4o and 4p with more than one minimum inhibitory concentration (MIC) value occurring between 16-64 µg mL-1, thus, in some cases better than the reference drug (fluconazole). SAR testing indicated that the presence of halogens and nitro substituents increases antifungal activity. Taken together, the results demonstrate that 2-aminothiophene derivatives are promising lead compounds for the development of antifungal drugs.

Documentos Relacionados

• Design, Synthesis, Pharmacological Evaluation and Molecular Docking Studies of Substituted Oxadiazolyl-2-Oxoindolinylidene Propane Hydrazide Derivatives
• Improvement of Solubility and Antifungal Activity of a New Aminothiophene Derivative by Complexation with 2-Hydroxypropyl-β-cyclodextrin
• Synthesis, in vitro Antifungal Activity and Molecular Modeling Studies of New Mannich Bases Derived from Lawsone
• New aminoporphyrins bearing urea derivative substituents: synthesis, characterization, antibacterial and antifungal activity
• Design, Synthesis and Antitubercular Activity of 2-(Benzylthio)-1H-benzo[d]imidazoles