Abstract:
:We designed and synthesized new pyrazole thiourea chimeric derivatives and confirmed their structures by NMR and IR spectra. Apoptotic effects were studied in human cancer cells. The N-[(1-methyl-1H-pyrazol-4-yl)carbonyl]-N'-(3-bromophenyl)-thiourea compound (4b) exhibited the highest apoptosis-inducing effect. Compound 4b and the thiazole derivatives, 5b and 6b, increased the expression of tumor necrosis factor receptors TRAIL-R2 and TRAIL-R1, accompanied by down-modulation of pro-caspase 3 levels, and the augmentation of cleaved caspase 3. They also reduced the levels of apoptosis inhibitory proteins and the expression of the heat-shock proteins Hsp27 and Hsp70. All the tested pyrazole derivatives induced a concentration-dependent increase of cells in G2/M phases. The analysis of the experimental data indicates the reduction of Akt phosphorylation as the most probable cellular mechanism of action for the tested compounds. The in vitro study indicated that compound 4b could be a promising anti-cancer drug, to be further developed in animal models of cancer.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Nitulescu GM,Draghici C,Olaru OT,Matei L,Ioana A,Dragu LD,Bleotu Cdoi
10.1016/j.bmc.2015.07.010subject
Has Abstractpub_date
2015-09-01 00:00:00pages
5799-808issue
17eissn
0968-0896issn
1464-3391pii
S0968-0896(15)00577-5journal_volume
23pub_type
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