TOPS-MODE based QSARs derived from heterogeneous series of compounds. Applications to the design of new herbicides.
A new application of TOPological Sub-structural MOlecular DEsign (TOPS-MODE) was carried out in herbicides using computer-aided molecular design. Two series of compounds, one containing herbicide and the other containing nonherbicide compounds, were processed by a k-Means Cluster Analysis in order to design the training and prediction sets. A linear classification function to discriminate the herbicides from the nonherbicide compounds was developed. The model correctly and clearly classified 88% of active and 94% of inactive compounds in the training set. More specifically, the model showed a good global classification of 91%, i.e., (168 cases out of 185). While in the prediction set, they showed an overall predictability of 91% and 92% for active and inactive compounds, being the global percentage of good classification of 92%. To assess the range of model applicability, a virtual screening of structurally heterogeneous series of herbicidal compounds was carried out. Two hundred eighty-four out of 332 were correctly classified (86%). Furthermore this paper describes a fragment analysis in order to determine the contribution of several fragments toward herbicidal property; also the present of halogens in the selected fragments were analyzed. It seems that the present TOPS-MODE based QSAR is the first alternate general "in silico" technique to experimentation in herbicides discovery.
Pérez González
Maykel
M
Chemical Bioactives Center, Central University of Las Villas, Santa Clara, C. P. 54830, Villa Clara, Cuba. maykel@cbq.uclv.edu.cu
Gonzalez Díaz
Humberto
H
Molina Ruiz
Reinaldo
R
Cabrera
Miguel A
MA
Ramos de Armas
Ronal
R
D016000:Cluster Analysis; D017076:Computer-Aided Design; D016208:Databases, Factual; D015195:Drug Design; D006540:Herbicides / Q000737:chemistry*; D008956:Models, Chemical; D009930:Organic Chemicals / Q000737:chemistry / Q000145:classification / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
D006540:Herbicides; D009930:Organic Chemicals