2-Phenyl-4-quinolone (YT-1) induces G2/M phase arrest and an intrinsic apoptotic mechanism in human leukemia cells

Abstract

The present study aimed to investigate the biological effects of the new compound 2‑phenyl‑4‑quinolone (YT‑1) on human leukemia cells. Cell viability was determined by propidium iodide (PI) exclusion method followed by flow cytometry. Our results showed that YT‑1 inhibited the cell viability and resulted in morphologic changes to the U937, HL‑60 and K562 cells, respectively. Among them, U937 cells were the most sensitive cell line. On the contrary, YT‑1 had no cytotoxic effects on human fetal skin fibroblast WS1 cells. Flow cytometric analysis indicated that YT‑1 induced G2/M phase arrest and apoptosis (sub‑G1 population) in U937 cells. The presence of apoptotic bodies evidenced by DAPI staining and DNA fragmentation detected by agarose gel electrophoresis further supported the induction of apoptosis in the YT‑1‑treated U937 cells. Annexin V/PI staining of U937 cells confirmed that the early apoptotic event occurred after YT‑1 exposure. YT‑1 disrupted the mitochondrial membrane potential (ΔΨm) in a time‑dependent manner. YT‑1 increased the protein levels of Bax and Bak but decreased Bcl‑2 and Bid protein levels in U937 cells in a time‑dependent manner. In addition, YT‑1 stimulated the expression of cytochrome c and proteolytic activation of caspase‑3 and caspase‑9 after exposure to YT‑1 in U937 cells. In summary, YT‑1 suppressed the viability of U937 leukemia cells through the intrinsic apoptosis pathway. YT‑1 is a potential chemotherapeutic candidate for the treatment of leukemia.

Synthesis of Natural and Unnatural Quinolones Inhibiting the Growth and Motility of Bacteria

“…Compound 5: 1 H NMR (600 MHz, methanol-d 4 ) δ 1.36 (t, J = 7.0 Hz, 3H), 4.04 (q, J = 7.0 Hz, 2H), 5.75 (d, J = 12.8 Hz, 1H), 6.33 (s, 1H), 7.35 (t, J = 7.5 Hz, 1H), 7.54 (d, J = 8.3 Hz, 1H), 7.62 (d, J = 12.8 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1 H), 8.16 (d, J = 8.3 Hz, 1H); 13 4-Methyl-3-((methylthio)methyl)quinolin-2(1H)-one (12). Following general procedure B, using compound 32 (375 mg, 1.58 mmol) as starting material, compound 12 was obtained as a pale yellow solid (312 mg, 90%); 1 3-(Methoxymethyl)-4-methylquinolin-2(1H)-one (13).…”

“…In order to expand the chemical space available for biological investigation, many researchers have taken a synthetic approach . Fluorinated 2-phenyl-4-quinolones have displayed potent cytotoxic properties, acting as tubulin inhibitors, while 2-phenyl-4-quinolone itself has been shown to induce G 2 /M phase arrest in a leukemia cell line . In 2007, a two-step synthetic procedure for the synthesis of quinolones was described, using a Cu-catalyzed Camps cyclization to produce a range of 2-substituted 4-quinolones .…”

“…10 Fluorinated 2-phenyl-4-quinolones have displayed potent cytotoxic properties, acting as tubulin inhibitors, 11 while 2-phenyl-4-quinolone itself has been shown to induce G 2 /M phase arrest in a leukemia cell line. 12 In 2007, a two-step synthetic procedure for the synthesis of quinolones was described, using a Cu-catalyzed Camps cyclization to produce a range of 2-substituted 4-quinolones. 13 A 2016 report described the synthesis of a range of HHQ and PQS derivatives in which the heteroatoms in the quinolone ring were replaced, 14 one of which displayed significant inhibitory properties against P. aeruginosa elastase, which is a key virulence factor for the microorganism and a potential drug target.…”