The neutral more hydrophobic form moves faster as a consequence

Similarly, compounds 44�C48 with a 4–piperazin-1-yl group Met-Enkephalin showed decreased potency than compounds 39�C43 with a 4-piperazin-1-yl group. For example, compound 43 inhibited A549 with an IC50 value of 1.26 mM, while compound 48 inhibited A549 with an IC50 value of 48.23 mM. These results indicated that an aryl susbtituent on the 4-piperaziny-1-yl group at the 2-position of the quinoxaline scaffold was unfavorable for antiproliferative activity. Besides, compounds with a long flexible piperazin-1-yl group showed potent low micromolar to nanomolar antiproliferative activity against three tested cancer cell lines. For instance, the tested IC50 values of compound 52 against PC3, A549 and HCT116 were 1.19, 0.34 and 0.22 mM, respectively. Piperazinylquinoxaline derivative 41 was further tested for its ability to induce apoptosis in PC3 cells. GDC0941, one of the most advanced PI3K inhibitors revealed so far, was used as the positive control. With an 1350456-56-2 chemical information apoptotic percent of 1.71 of the control, the percent of apoptotic PC3 cells induced by compound 41 and GDC0941 in 5 mM after treatment of 24 h were 4.48 and 3.12, respectively. The fact that compound 41 showed an apoptotic percent of 32.83 in 10 mM, in comparison with that of 5.85 for GDC0941, indicated the potent apoptosis inductive activity of compound 41. Cell cycle arrest. Moreover, flow cytometric analysis was performed to determine whether target compounds could induce cell cycle arrest in PC3 cells. GDC0941 was used as the positive control. PC3 cells were treated with compound 41 and GDC0941 in two different concentrations for 24 h, the results are presented as Figure 6. GDC0941 induced cell cycle arrest in G1 phase with a simultaneous decrease of cells in S phase. Compound 41 showed similar trend while the percent of cell in G1 phase was smaller. Pin1 interacting with neverin-mitosis A kinase-1) was discovered in 1996 as a PPIase enzyme that regulates mitosis. The two domains of Pin1, a WW and a PPIase domain, are connected by a flexible linker that serves as a communication conduit between the domains. Both of these domains recognize the phospho-Ser/Thr-Pro bonds present in mitotic phosphoproteins. Pin1 is distinct from two other PPIase families, cyclophilin and FK506 binding protein, since Pin1 only has PPIase activity for phosphorylated substrates. Pin1 catalyzes prolyl cis-trans isomerization to function as a molecular timer regulating the cell cycle, cell signaling, gene expression, immune response, and neuronal function. Pin1 is overexpressed in many cancer lines, and plays an important role in oncogenesis.