<?xml version='1.0' encoding='UTF-8'?><xml><records><record><source-app name="HighWire" version="7.x">Drupal-HighWire</source-app><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">ISHIHARA, MARIKO</style></author><author><style face="normal" font="default" size="100%">HATANO, HAJIME</style></author><author><style face="normal" font="default" size="100%">TAKEKAWA, FUMIHIRO</style></author><author><style face="normal" font="default" size="100%">KAWASE, MASAMI</style></author><author><style face="normal" font="default" size="100%">SAKAGAMI, HIROSHI</style></author></authors><secondary-authors></secondary-authors></contributors><titles><title><style face="normal" font="default" size="100%">Estimation of Relationship Between Descriptors and Cytotoxicity of Newly Synthesized 1,2,3,4-Tetrahydroisoquinoline Derivatives</style></title><secondary-title><style face="normal" font="default" size="100%">Anticancer Research</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2009</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2009-10-01 00:00:00</style></date></pub-dates></dates><pages><style  face="normal" font="default" size="100%">4077-4082</style></pages><volume><style face="normal" font="default" size="100%">29</style></volume><issue><style face="normal" font="default" size="100%">10</style></issue><abstract><style  face="normal" font="default" size="100%">We recently demonstrated that the cytotoxicity of nineteen 1,2,3,4-tetrahydroisoquinoline derivatives depends on the molecular size (surface are, volume, width measured at 3-dimensional configuration), but not on most of the other electronic factors (Ishihara et al., Anticancer Res 29: 2265-2272, 2009). However, the information regarding cytotoxicity and molecular size in these compounds is limited. Here, a quantitative structure-activity relationship (QSAR) analysis using nineteen newly synthesized 1,2,3,4-tetrahydroisoquinoline derivatives was carried out. A semiempirical molecular-orbital method (CAChe 4.9, PM5) was applied to delineate the relationship between the cytotoxicity (evaluated by 50% cytotoxic concentration, CC50) of the nineteen derivatives (TD1-19) against human promyelocytic leukemia HL-60 and human oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4) cell lines and sixteen chemical descriptors determined by CONFLEX/PM5 method or the molecular weight. There was some correlation between the CC50 and the dipole moment for HSC-4 cells (r2=0.273), between the CC and log P for HL-60 and HSC-3 cells (r2 50 =0.191-0.212), and between the CC50 and distance of C-R2 (at three dimensional configuration) (r2=0.394) and molecular weight (r2=0.292) for HL-60 cells. On the other hand, there was little or no correlation between the CC50 and other descriptors. The present study demonstrated the dependency of the cytotoxicity of 1,2,3,4-tetrahydroisoquinoline derivatives on hydrophobicity and distance between C-R2 in the 3-dimensional configuration. These descriptors obtained from the CONFLEX/PM5 method may be utilized as a tool to analyze the biological effect of 1,2,3,4-tetrahydroisoquinolines.</style></abstract></record></records></xml>