RT Journal Article
SR Electronic
T1 Estimation of Relationship Between Descriptors and Cytotoxicity of Newly Synthesized 1,2,3,4-Tetrahydroisoquinoline Derivatives
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4077
OP 4082
VO 29
IS 10
A1 ISHIHARA, MARIKO
A1 HATANO, HAJIME
A1 TAKEKAWA, FUMIHIRO
A1 KAWASE, MASAMI
A1 SAKAGAMI, HIROSHI
YR 2009
UL http://ar.iiarjournals.org/content/29/10/4077.abstract
AB 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.