Synthesis and cytotoxicity of novel dispiro derivatives of 5-arylidenoxazolones, potential inhibitors of p53—MDM2 protein-protein interaction

Journal Article · Thu Mar 15 04:00:00 EDT 2018 · Russian Chemical Bulletin

DOI:https://doi.org/10.1007/S11172-018-2111-X· OSTI ID:22863354

Beloglazkina, A. A.; Skvortsov, D. A.; Tafeenko, V. A.; Majouga, A. G.; Zyk, N. V.

Regioselective synthesis of new dispiro indolinones combining both an indolinone and an oxazolone fragment in their structure comprised the 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from isatin and sarcosine, at 2-aryl-5-arylmethylidene-substituted 1,3-oxazol-5(4H)-ones. When ortho and para halogen atoms were present in the aromatic substituents of the starting oxazolones, complex mixtures containing large amounts of oxazoline ring opening products and their dispiro derivatives were formed. The cytotoxicity of compounds was tested by MTT on LNCaP, PC3, HCT116, MCF7, A549, HEK, and VA13 cell lines. The compound possessing the best cytotoxicity revealed the IC{sub 50} = 1.08±0.96 μM towards the p53- expressing LNCaP cells and lower activity (IC50 = 3.21±1.45 μM) towards the non-expressing p53 protein PC3 cells, however, it has proved inactive towards the HCT cells, both expressing (HCТ+/+) and non-expressing (HCT–/–) p53.

• OSTI ID: 22863354
• Journal Information: Russian Chemical Bulletin, Journal Name: Russian Chemical Bulletin Journal Issue: 3 Vol. 67; ISSN RCBUEY; ISSN 1066-5285
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
AROMATICS
HALOGENS
MIXTURES
MOLECULE-MOLECULE COLLISIONS
PROTEINS
SARCOSINE
SYNTHESIS
TOXICITY