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Synthesis, in vitro antigiardial activity, SAR analysis and docking study of substituted chalcones

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A series of 15 chalcones-bearing substituents at positions 2, 4, and 5 of rings A and B were synthesized using microwave-assisted Claissen–Smichdt condensation and evaluated for their activity against Giardia lamblia and Green monkey kidney cells. Five compounds exhibited activity against G. lamblia at IC50’s <5 μM. The chalcone 3m exhibited the highest antigiardial activity (IC50 = 1.03 μM), even more than the positive control (metronidazole, IC50 = 1.4 μM), and selectivity (SI = 38.9). A preliminary SAR study suggested that electrophylicity has not relationship with antigiardiasic activity, and the docking study reveals that synthesized chalcones bind at zone 3 of colchicine site, therefore presumably the action mechanism of the synthesized chalcones does not follow the Michael acceptor mechanism.

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Funding for this research was provided by Facultad de Química, Universidad Autónoma de Yucatan. The docking analysis was performed as part of the research project 256657 granted by the Consejo Nacional de Ciencia y Tecnología - México (CONACYT). In memory of Dr. José Antonio Manzanilla Cano (1964-2015), for his invaluable support.

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Correspondence to Gonzalo J. Mena-Rejón.

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Cáceres-Castillo, D., Carballo, R.M., Quijano-Quiñones, R. et al. Synthesis, in vitro antigiardial activity, SAR analysis and docking study of substituted chalcones. Med Chem Res 29, 431–441 (2020). https://doi.org/10.1007/s00044-019-02492-5

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  • Synthesis
  • Substituted chalcones
  • Antigiardial activity
  • SAR analysis
  • Docking study