Structure-cytotoxicity relationships for a series of HEPT derivatives.
Structure-cytotoxicity relationships were studied for a series of 90 HEPT derivatives by means of multiple linear regression (MLR) and artificial neural network (ANN) techniques. The values of log(1/CC50) (CC50=cytotoxic dose of compound required to reduce the proliferation of normal uninfected MT-4 cells by 50%) of the studied compounds were correlated with the descriptors encoding the chemical structures. Using the pertinent descriptors revealed by the regression analysis, a correlation coefficient of 0.935 ( s=0.149) for the training set ( n=81) was obtained for the ANN model with a 5-6-1 configuration. The results obtained from this study indicate that the cytotoxicity of HEPT derivatives is strongly dependent on hydrophobic factors, mainly log P(R1), and dependent on the steric factors, especially SigmaMW(R3+R4). Comparison of the descriptors' contribution obtained in MLR and ANN analysis shows that the contribution of some of the descriptors to cytotoxicity may be non-linear.
Bazoui
Halima
H
Laboratoire de Chimie Organique Appliquée et Catalyse, Faculté des Sciences Ben M'Sik, B.P. 7955, Sidi Othmane, Casablanca, Morocco.
Zahouily
Mohamed
M
Sebti
Saïd
S
Boulajaaj
Saïd
S
Zakarya
Driss
D
D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016014:Linear Models; D016571:Neural Networks, Computer; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000633:toxicity*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C061818:1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine; D013941:Thymine