Hybrid molecules based on an emodin scaffold. Synthesis and activity against SARS-CoV-2 and Plasmodium - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Organic & Biomolecular Chemistry Année : 2023

Hybrid molecules based on an emodin scaffold. Synthesis and activity against SARS-CoV-2 and Plasmodium

Résumé

Since the Covid-19 epidemic, it has been clear that the availability of small and affordable drugs that are able to efficiently control viral infections in humans is still a challenge in medicinal chemistry. The synthesis and biological activities of a series of hybrid molecules that combine an emodin moiety and other structural moieties expected to act as possible synergistic pharmacophores in a single molecule were studied. Emodin has been reported to block the entry of the SARS-CoV-2 virus into human cells and might also inhibit cytokine production, resulting in the reduction of pulmonary injury induced by SARS-CoV-2. The pharmacophore associated with emodin was either a polyamine residue (emodin-PA series), a choice driven by the fact that a natural alkyl PA like spermine and spermidine play regulatory roles in immune cell functions, or a diphenylmethylpiperazine derivative of the norchlorcyclizine series (emoxyzine series). In fact, diphenylmethylpiperazine antagonists of the H1 histamine receptor display activity against several viruses by multiple interrelated mechanisms. In the emoxyzine series, the most potent drug against SARS-CoV-2 was (R)-emoxyzine-2, with an EC50 value = 1.9 μM, which is in the same range as that of the reference drug remdesivir. However, the selectivity index was rather low, indicating that the dissociation of antiviral potency and cytotoxicity remains a challenge. In addition, since emodin was also reported to be a relatively high-affinity inhibitor of the virulence regulator FIKK kinase from the malaria parasite Plasmodium vivax, the antimalarial activity of the synthesized hybrid compounds has been evaluated. However, these molecules cannot efficiently compete with the currently used antimalarial drugs.
Fichier principal
Vignette du fichier
Li, Hybrid molecules based on an emodin, 2023.pdf (946.36 Ko) Télécharger le fichier
Origine : Publication financée par une institution
Licence : CC BY - Paternité

Dates et versions

hal-04201757 , version 1 (20-09-2023)

Licence

Paternité

Identifiants

Citer

Youzhi Li, Franck Touret, Xavier de Lamballerie, Michel Nguyen, Marion Laurent, et al.. Hybrid molecules based on an emodin scaffold. Synthesis and activity against SARS-CoV-2 and Plasmodium. Organic & Biomolecular Chemistry, 2023, 21 (36), pp.7382-7394. ⟨10.1039/D3OB01122D⟩. ⟨hal-04201757⟩
48 Consultations
11 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More