Structure activity relationship between calculated molecular properties and biological activities against Leishmania donovani of the natural neolignan analogues studied with pattern recognition techniques: a possible explanation for the activity/inactivity of some neolignans

Structure activity relationship (SAR) between calculated molecular properti es and biological activities against Leishimania donovani of 20 analogues o f the natural neolignans was studied. Since the arginine residue in the ade nosine-kinase from Leishmania donovani is a possible receptor of the neolig nans, fitting of some neolignans with the arginine was performed in order t o define the binding sites of neolignans. The ab initio Hatree-Fock method was employed to calculate the molecular properties of the 20 analogues. Fou r different pattern recognition techniques such as principal component anal ysis, SIMCA, etc. were used to establish SAR. The compounds were classified correctly in 95% of success by SIMCA, more than 80% of success by the othe r three methods. The neolignans that have the aromatic rings substituted in the ortho and/or para positions are generally active. It was demonstrated that SAR studies were possible using the calculated molecular properties. ( C) 2001 Elsevier Science B.V. All rights reserved.