The development of 3D-QSAR study and recursive partitioning of heterocyclic quinone derivatives with antifungal activity.
It was reported that some 1,4-quinone derivatives such as 6-(N-arylamino)-7-chloro/6,7-bis[S-(aryl)thio]-5,8-quinolinedione and 6-arylthio-/5,6-arylamino-4,7-dioxobenzothiazoles have antifungal effects. To understand the structural basis for antifungal activity and guide in the design of more potent agents, we performed three-dimensional quantitative structure-activity relationship studies for a series of compounds using comparative molecular field analysis (CoMFA). The MIC values of 1,4-quinone derivatives on Aspergillus niger exhibited a strong correlation with steric and electrostatic factors of the 3D structure of molecules. The statistical results of the training set, cross-validated q(2) (0.683) and conventional r(2) (0.877) values, gave reliability to the prediction of inhibitory activity of a series of compounds. We also performed recursive partitioning (RP) analysis, used for the classification of molecules with activity using CART methods. Physicochemical, structural, and topological connectivity indices and E-state key descriptors were used for obtaining the decision tree models. The decision tree could classify the inhibitory activity of 1,4-quinone derivatives and its essential descriptors were S_aaN, Hbond donor, and Kappa-3.
Choi
Su-Young
SY
School of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.
Shin
Jae Hong
JH
Ryu
Chung Kyu
CK
Nam
Ky-Youb
KY
No
Kyoung Tai
KT
Park Choo
Hea-Young
HY
D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001234:Aspergillus niger / Q000187:drug effects* / Q000378:metabolism; D003627:Data Interpretation, Statistical; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D021281:Quantitative Structure-Activity Relationship; D011809:Quinones / Q000737:chemistry / Q000494:pharmacology*
D000935:Antifungal Agents; D011809:Quinones