Biologically active carbazole derivatives: focus on oxazinocarbazoles and related compounds.
Four series of carbazole derivatives, including N-substituted-hydroxycarbazoles, oxazinocarbazoles, isoxazolocarbazolequinones, and pyridocarbazolequinones, were studied using diverse biological test methods such as a CE-based assay for CK2 activity measurement, a cytotoxicity assay with IPC-81 cell line, determination of MIC of carbazole derivatives as antibacterial agents, a Plasmodium falciparum susceptibility assay, and an ABCG2-mediated mitoxantrone assay. Two oxazinocarbazoles Ib and Ig showed CK2 inhibition with IC50 = 8.7 and 14.0 µM, respectively. Further chemical syntheses were realized and the 7-isopropyl oxazinocarbazole derivative 2 displayed a stronger activity against CK2 (IC50 = 1.40 µM). Oxazinocarbazoles Ib, Ig, and 2 were then tested against IPC-81 leukemia cells and showed the ability to induce leukemia cell death with IC50 values between 57 and 62 μM. Further investigations were also reported on antibacterial and antiplasmodial activities. No significant inhibitory activity on ABCG2 efflux pump was detected.
EA 4446 Biomolécules Cancer et Chimiorésistances, Faculté de Pharmacie - ISPB, Université Lyon 1 , Lyon , France .
Zouhair
Z
Bouaziz
Samar
S
Issa
Jacques
J
Gentili
Andreas
A
Gratz
Andre
A
Bollacke
Matthias
M
Kassack
Joachim
J
Jose
Lars
L
Herfindal
Gro
G
Gausdal
Stein Ove
SO
Døskeland
Catherine
C
Mullié
Pascal
P
Sonnet
Camille
C
Desgrouas
Nicolas
N
Taudon
Glaucio
G
Valdameri
Attilio
A
Di Pietro
Milad
M
Baitiche
Marc
M
Le Borgne
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000962:Antimalarials; D000970:Antineoplastic Agents; D002227:Carbazoles; D010078:Oxazines; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C
Biological activities; carbazoles; chemical synthesis; oxazinocarbazoles; screening