• Biomolecules & Therapeutics
• /
• v.27 no.5
• /
• pp.492-501
• /
• 2019

Nitrogen-containing heterocycles such as quinoline, quinazolinones and indole are scaffolds of natural products and have broad biological effects. During the last years those structures have been intensively synthesized and modified to yield new synthetic molecules that can specifically inhibit the activity of dysregulated protein kinases in cancer cells. Herein, a series of newly synthesized isoquinolinamine (FX-1 to 8) and isoindoloquinazolinone (FX-9, FX-42, FX-43) compounds were evaluated in regards to their anti-leukemic potential on human B- and T- acute lymphoblastic leukemia (ALL) cells. Several biological effects were observed. B-ALL cells (SEM, RS4;11) were more sensitive against isoquinolinamine compounds than T-ALL cells (Jurkat, CEM). In SEM cells, metabolic activity decreased with $10{\mu}M$ up to 26.7% (FX-3), 25.2% (FX-7) and 14.5% (FX-8). The 3-(p-Tolyl) isoquinolin-1-amine FX-9 was the most effective agent against B- and T-ALL cells with IC50 values ranging from 0.54 to $1.94{\mu}M$. None of the tested compounds displayed hemolysis on erythrocytes or cytotoxicity against healthy leukocytes. Anti-proliferative effect of FX-9 was associated with changes in cell morphology and apoptosis induction. Further, influence of FX-9 on PI3K/AKT, MAPK and JAK/STAT signaling was detected but was heterogeneous. Functional inhibition testing of 58 kinases revealed no specific inhibitory activity among cancer-related kinases. In conclusion, FX-9 displays significant antileukemic activity in B- and T-ALL cells and should be further evaluated in regards to the mechanisms of action. Further compounds of the current series might serve as templates for the design of new compounds and as basic structures for modification approaches.

• Korean Journal of Weed Science
• /
• v.12 no.2
• /
• pp.110-123
• /
• 1992

To investigate the safening effect of dymron against cinosulfuron, the responses of 104 rice cultivars and lines to single and mixture treatments of cinosulfuron [3-(4.6-dimethoxy-1,3,5-triazin-2-yl)-1-[2-(2-methoxyethoxy)-phenylsulfonyl]-urea] and dymron [1-(${\alpha}$, ${\alpha}$-dimethylbenzyl)-3-p-tolyl urea] were evaluated. The responses of 104 rice cultivars and lines to cinosulfuron were differed. Among the rice cultivars, growth of Calrose, Dasukei, Hwajinhyeo, and Milyang 105 was significantly inhibited by cinosulfuron but there was no inhibition in Daeseongbyeo, Iri 371, Jangseongbyeo, Taebaegbyeo and IR 74. The japonica types were generally inhibited more than the indica and indica${\times}$japonica types. When Kwangmyungbyeo was treated with the mixtures of cinosulfuron 48g and 96g ai/ha with dymron 450g ai/ha, the inhibition of plant height was significantly reduced regardless of dymron concentrations. With increase in cinosulfuron concentration, the safening effect of dymron against cinosulfuron was more evident in plant height than fresh weight. On the other hand, dymron did not have any safening effects of cinosulfuron on Echinochloa crus-galli at any concentrations. The mixtures of dymron and cinosulfuron produced antagonistic effects on the plant height regardless of rice cultivars and treatment concentrations. At cinosulfuron 24g ai/ha, the effects of the mixtures of cinosulfuron and brassinolide on the plant height of Kwangmyungbyeo and IR 74 were similar irrespective of brassinolide concentrations but the inhibition of Kwangmyungbyeo was greater than that of IR 74 as the concentrations of cinosulfuron increased. The effects of the mixtures of cinosulfuron at concentration of 96g ai/ha with various ABA levels on the plant height of both Kwangmyungbyeo and IR 74 showed synergistic effect regardless of ABA concentration. However, the response of fresh weight of both cultivars treated with cinosulfuron at 96g ai/ha with ABA synergisism was observed in Kwangyungbyeo while IR 74 showed antagonism.