Találati lista | Tudóstér

001-es BibID:	BIBFORM077772
035-os BibID:	(cikkazonosító)2845 (WoS)000451641900117 (Scopus)85056048074
Első szerző:	Szebeni Gábor János (Szeged)
Cím:	Imidazo[1,2-b]pyrazole-7-carboxamides Induce Apoptosis in Human Leukemia Cells at Nanomolar Concentrations / Gábor J. Szebeni, József A. Balog, András Demjén, Róbert Alföldi, Vanessza L. Végi, Liliána Z. Fehér, Imola Mán, Edit Kotogány, Barbara Gubán, Péter Batár, László Hackler Jr., Iván Kanizsai, László G. Puskás
Dátum:	2018
ISSN:	1420-3049
Megjegyzések:	Leukemia, the malignancy of the hematopoietic system accounts for 10% of cancer cases with poor overall survival rate in adults; therefore, there is a high unmet medical need for the development of novel therapeutics. Eight imidazo[1,2-b]pyrazole-7-carboxamides have been tested for cytotoxic activity against five leukemia cell lines: Acute promyelocytic leukemia (HL-60), acute monocytic leukemia (THP-1), acute T-lymphoblastic leukemia (MOLT-4), biphenotypic B myelomonocytic leukemia (MV-4-11), and erythroleukemia (K-562) cells in vitro. Imidazo[1,2-b]pyrazole-7-carboxamides hampered the viability of all five leukemia cell lines with different potential. Optimization through structure activity relationship resulted in the following IC50 values for the most effective lead compound DU385: 16.54 nM, 27.24 nM, and 32.25 nM on HL-60, MOLT-4, MV-4-11 cells, respectively. Human primary fibroblasts were much less sensitive in the applied concentration range. Both monolayer or spheroid cultures of murine 4T1 and human MCF7 breast cancer cells were less sensitive to treatment with 1.5⁻10.8 ?M IC50 values. Flow cytometry confirmed the absence of necrosis and revealed 60% late apoptotic population for MV-4-11, and 50% early apoptotic population for HL-60. MOLT-4 cells showed only about 30% of total apoptotic population. Toxicogenomic study of DU385 on the most sensitive MV-4-11 cells revealed altered expression of sixteen genes as early (6 h), midterm (12 h), and late response (24 h) genes upon treatment. Changes in ALOX5AP, TXN, and SOD1 expression suggested that DU385 causes oxidative stress, which was confirmed by depletion of cellular glutathione and mitochondrial membrane depolarization induction. Imidazo[1,2-b]pyrazole-7-carboxamides reported herein induced apoptosis in human leukemia cells at nanomolar concentrations.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk acute myeloid leukemia apoptosis imidazole pyrazole toxicogenomics
Megjelenés:	Molecules. - 23 : 11 (2018), p. 1-15. -
További szerzők:	Balog József A. Demjén András Alföldi Róbert Végi Vanessza L. Fehér Liliána Z. (Szeged) Mán Imola Kotogány Edit Gubán Barbara Batár Péter (1969-) (belgyógyász, haematológus) Hackler László Jr. Kanizsai Iván Puskás László G.
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: