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

Abstract

Structure activity relationship (SAR) between calculated molecular properties and biological activities against Leishimania donovani of 20 analogues of the natural neolignans was studied. Since the arginine residue in the adenosine-kinase from Leishmania donovani is a possible receptor of the neolignans, fitting of some neolignans with the arginine was performed in order to define the binding sites of neolignans. The ab initio Hatree–Fock method was employed to calculate the molecular properties of the 20 analogues. Four different pattern recognition techniques such as principal component analysis, 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 other 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.