Synthesis, Antifungal Evaluation, and Structure–activity Relationship of Chlorinated Imidazopyridinyl- phenylpropenone Derivatives against Aspergillus fumigatus
Deto Ursul Jean-Paul N’guessan *
Department of Therapeutic Chemistry and Organic Chemistry, UFR Pharmaceutical and Biological, Côte d’Ivoire.
Songuigama Coulibaly
Department of Therapeutic Chemistry and Organic Chemistry, UFR Pharmaceutical and Biological, Côte d’Ivoire.
Avi Tanguy Kouao
Department of Therapeutic Chemistry and Organic Chemistry, UFR Pharmaceutical and Biological, Côte d’Ivoire.
Alain A. Kacou
Department of Therapeutic Chemistry and Organic Chemistry, UFR Pharmaceutical and Biological, Côte d’Ivoire.
Kpongbo Etienne Angora
Department of Parasitology and Mycology, UFR Pharmaceutical and Biological Sciences, Felix Houphouët-Boigny University, 01 BP V34 Abidjan, Côte d’Ivoire and Laboratory of Parasitology of the Angré University Hospital, Abidjan, Côte d'Ivoire.
Fabrice Koffi
Department of Therapeutic Chemistry and Organic Chemistry, UFR Pharmaceutical and Biological, Côte d’Ivoire.
Ismaila Diallo
Department of Therapeutic Chemistry and Organic Chemistry, UFR Pharmaceutical and Biological, Côte d’Ivoire.
Mahama Ouattara
Department of Therapeutic Chemistry and Organic Chemistry, UFR Pharmaceutical and Biological, Côte d’Ivoire.
*Author to whom correspondence should be addressed.
Abstract
Background: Aspergillus fumigatus is the leading causative agent of invasive aspergillosis, a deadly opportunistic fungal infection in immunocompromised patients. The increasing emergence of azole-resistant strains necessitates the urgent development of new antifungal molecules.
Objective: This study reports the synthesis, structural characterization, and evaluation of the antifungal activity of ten novel chlorinated chalcone-imidazo[1,2-a]pyridine hybrid derivatives against a clinical strain of A. fumigatus.
Methods: The compounds were synthesized by Claisen-Schmidt condensation between acetylated imidazo[1,2-a]pyridine derivatives and various substituted aromatic aldehydes. Structural characterization was performed by ¹H and ¹³C NMR. Antifungal activity was determined by microplate scattering with calculation of minimum inhibitory concentrations (MICs).
Results: Ten compounds were obtained with varying yields (45– 83%). Spectral analysis confirmed the formation of α,β-unsaturated structures with E geometry. The MICs ranged from 73.16 to 319.74 µM, with optimal activity for the 3-nitro derivative (MIC = 73.16 µM) and the Chlorinated derivatives (MIC = 75.48 µM). The 2-methoxyphenyl derivative (MIC = 76.50 µM) and the unsubstituted compound (MIC = 84.27 µM) show promising activity.
Conclusion: Structure-activity relationship studies reveal the importance of lipophilicity and steric hindrance. These chalcone-imidazopyridine hybrids represent promising structures for the development of new antifungal agents against A. fumigatus.
Keywords: Aspergillus fumigatus, chalcone, imidazo[1,2-a]pyridine, antifungal, structure-activity relationship, azole resistance