Design and Synthesis of Novel N-Benzylidene Derivatives of 3-Amino-4-imino-3,5-dihydro-4H-chromeno[2,3-d]pyrimidine under Microwave, In Silico ADME Predictions, In Vitro Antitumoral Activities and In Vivo Toxicity - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue (Article De Synthèse) Pharmaceuticals Année : 2024

Design and Synthesis of Novel N-Benzylidene Derivatives of 3-Amino-4-imino-3,5-dihydro-4H-chromeno[2,3-d]pyrimidine under Microwave, In Silico ADME Predictions, In Vitro Antitumoral Activities and In Vivo Toxicity

Sirine Karoui
  • Fonction : co premier-auteur
  • PersonId : 1372700
Marwa Dhiabi
  • Fonction : Auteur
  • PersonId : 1372701
Mehdi Fakhfakh
  • Fonction : Auteur
  • PersonId : 1372702
Souhir Abid
  • Fonction : Collaborateur
  • PersonId : 1211871
Emmanuelle Limanton
  • Fonction : Collaborateur
  • PersonId : 1372703
Rémy Le Guével
  • Fonction : Collaborateur
  • PersonId : 1372704
Ludovic Paquin
  • Fonction : Collaborateur
  • PersonId : 1192542
Houcine Ammar
  • Fonction : Auteur
  • PersonId : 1372707

Résumé

The synthesis of a series of new N-benzylidene derivatives of 3-amino-4-imino-3,5-dihydro-4H-chromeno[2,3-d]pyrimidine 10(a-l) bearing two points of molecular diversity is reported. These new compounds were synthesized in five steps including two steps under microwave dielectric heating. They were fully characterized using 1H and 13C NMR, FTIR and HRMS. The in silico physicochemical properties of compounds 10(a-l) were determined according to Lipinski’s rules of five (RO5) associated with the prediction of their bioavailability. These new compounds 10(a-l) were tested for their antiproliferative activities in fibroblasts and eight representative human tumoral cell lines (Huh7 D12, Caco2, MDA-MB231, MDA-MB468, HCT116, PC3, MCF7 and PANC1). Among them, the compounds 10h and 10i showed sub-micromolar cytotoxic activity on tumor cell lines (0.23 < IC50 < 0.3 μM) and no toxicity on fibroblasts (IC50 > 25 μM). A dose-dependent inhibition of Store-Operated Ca+2 Entry (SOCE) was observed in the HEK293 cell line with 10h. In vitro embryotoxicity and angiogenesis on the mCherry transgenic zebrafish line showed that 10h presented no toxic effect and no angiogenic effect on embryos with a dose of 5 μM at 72 hpf.
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hal-04537617 , version 1 (08-04-2024)

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Sirine Karoui, Marwa Dhiabi, Mehdi Fakhfakh, Souhir Abid, Emmanuelle Limanton, et al.. Design and Synthesis of Novel N-Benzylidene Derivatives of 3-Amino-4-imino-3,5-dihydro-4H-chromeno[2,3-d]pyrimidine under Microwave, In Silico ADME Predictions, In Vitro Antitumoral Activities and In Vivo Toxicity. Pharmaceuticals, 2024, 17 (4), pp.458. ⟨10.3390/ph17040458⟩. ⟨hal-04537617⟩
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