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Synthesis, and discovery of a potential anti-HepG2 agents: Coumarin derivatives containing 3-Aryl isoxazolyl moiety.
- Source :
-
Journal of Molecular Structure . Oct2023, Vol. 1290, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- • Twenty- five coumarin-isoxazole derivatives were highly synthesized by [3+ 2] cycloaddition reaction. • The benzene ring of oximes (b4 - b5) was chlorinated to obtain imidoyl chlorides (c4-c5). • The structure of MC-16 was confirmed by X- ray. • MC-14 (IC50 = 12.85 μM/ L, SI= 11.23) exhibited selecteive cytotoxicity against HepG2 cell line. • Docking study between bioactive compounds and protein residue of tubulin (PDB ID: 6O5N) was performed. In here, a series of coumarin-isoxazole derivatives were synthesized, characterized by spectroscopy technologies and evaluated for their cytotoxicity against HepG2 cell lines. Meanwhile, eight bioactive compounds were also evaluated for their toxicity on normal Vero cell lines. MC-16 , a monoclinic crystal with P21/c space group, was further confirmed by X-ray and 2D-NMR. Results demonstrated that b5 was reacted with 7 equivalents NCS to given c5, and then MC-16 was obtained by the reaction of nitrile oxides derivatized from c5 with e1 , passing intermediate state TS1. Bioactive results indicated that eight compounds (MC-2, MC-4, MC-5, MC-9, MC-10, MC-14, MC-19 and MC-20) exhibited weak to strong cytotoxicity against HepG2 cell lines, and their toxicity to Vero cells was much lower than that of Cisplatin (IC 50 (HpeG2) = 8.44 μM/ L, IC 50 (Vero) = 28.63 μM/ L, SI= 3.39). Among them, MC-14 (IC 50 (HpeG2) = 12.85 μM/ L, IC 50 (Vero) = 144.32 μM/ L, SI= 11.23) owned the strongest anti- HepG2 activity and obviously induced apoptosis under 48 μM. Structure-relationship analysis displayed that substituent group R = Cl or Br was the key factors to enhance the anti-HepG2 activity. The docking results revealed that bioactive compounds can effectively interacted with protein (PDB ID: 6O5N). [Display omitted] [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00222860
- Volume :
- 1290
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular Structure
- Publication Type :
- Academic Journal
- Accession number :
- 164345484
- Full Text :
- https://doi.org/10.1016/j.molstruc.2023.135892