The Synthesis of 2′-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities

Imen Abid (1, 2) , Wassim Moslah (3, 4) , Sandrine Cojean (5, 6) , Nicolas Imbert (5) , Philippe M Loiseau (5) , Alain Chamayou (2) , Najet Srairi-Abid (3, 4) , Rachel Calvet (2) , Michel Baltas (1, 7)

1 LCC - Laboratoire de chimie de coordination
2 RAPSODEE - Centre de recherche d'Albi en génie des procédés des solides divisés, de l'énergie et de l'environnement
3 Biomolécules, Venins et Applications Théranostiques [Tunis]
4 UTM - Université de Tunis El Manar
5 BioCIS - Biomolécules : Conception, Isolement, Synthèse
6 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
7 ERL1289 - New Antimalarial Molecules and Pharmacological Approaches

Chalcones are polyphenols that belong to the flavonoids family, known for their broad pharmacological properties. They have thus attracted the attention of chemists for their obtention and potential activities. In our study, a library of compounds from 2′-hydroxychalcone’s family was first synthesized. A one-step mechanochemical synthesis via Claisen–Schmidt condensation reaction under ball mill conditions was studied, first in a model reaction between a 5′-fluoro-2′-hydroxyacetophenone and 3,4-dimethoxybenzaldehyde. The reaction was optimized in terms of catalysts, ratio of reagents, reaction time, and influence of additives. Among all assays, we retained the best one, which gave the highest yield of 96% when operating in the presence of 1 + 1 eq. of substituted benzaldehyde and 2 eq. of KOH under two grinding cycles of 30 min. Thus, this protocol was adopted for the synthesis of the selected library of 2′-hydroxychalcones derivatives. The biological activities of 17 compounds were then assessed against Plasmodium falciparum, Leishmania donovani parasite development, as well as IGR-39 melanoma cell lines by inhibiting their viability and proliferation. Compounds 6 and 11 are the most potent against L. donovani, exhibiting IC50 values of 2.33 µM and 2.82 µM, respectively, better than the reference drug Miltefosine (3.66 µM). Compound 15 presented the most interesting antimalarial activity against the 3D7 strain, with IC50 = 3.21 µM. Finally, chalcone 12 gave the best result against IGR-39 melanoma cell lines, with an IC50 value of 12 µM better than the reference drug Dacarbazine (IC50 = 25 µM).

Mots clés: Ball mill mechanochemistry; Sustainable synthesis; Chalcones; Phenolics; Antiparasitic; Antitumoral

Domaines: Chimie thérapeutique

Imen Abid, Wassim Moslah, Sandrine Cojean, Nicolas Imbert, Philippe M Loiseau, et al.. The Synthesis of 2′-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities. Molecules, 2024, 29 (8), pp.1819. ⟨10.3390/molecules29081819⟩. ⟨hal-04550832⟩