Kızılcan, Dilek Şeyma; Türkmenoğlu, Burçin; Güzel, Yahya

The interaction between Ligand-Receptor (L-R) to solve the pharmacological and toxicological problems of enantioselective molecules was studied as 3D Quantitative Structure-Activity Relationship (3D-QSAR). The biological activity of enantiomers of stereo isomeric molecules that differ in 3D can only be determined by the Local Reactive Descriptor (LRD). The parameters of the Pharmacophore (Pha) on the receptor side can be determined using LRDs of atoms of the molecule in 3D space. “Klopman index,” which was brought to the literature as LRD by us, was compared with typical LRD descriptors such as atom charge, Fukui index, frontier orbital coefficients (HOMO/LUMO) in our Molecular Conformer Electron Topological (MCET) program. After predicting the 3D-QSAR model with the Leave One Out-Cross Validation (LOO-CV) technique on the molecules in the training set, the model was validated on the molecules in the external test set. Statistical results from both sets were evaluated for all LRDs, and the best results were obtained as Q2 = 0.955 and R2= 0.964 in the Klopman index.

Kızılcan, Dilek Şeyma; Türkmenoğlu, Burçin; Güzel, Yahya

We present the Klopman index, which is effective in explaining the mechanisms of organic chemistry, in quantitative structure activity relationship (QSAR) studies on flavonoids as a new descriptor for the first time. Instead of using random descriptors to elucidate the interactions between the ligand and the receptor, the atomic local reactive descriptor (LRD) which we call as the Klopman index in our molecular conformer electron topological (MCET) program was used. Both the atomic charges and the frontier orbital coefficients are used simultaneously in the Klopman index. Substrate-aromatase interactions of strong aromatase inhibitors against estrogen-dependent breast cancer were investigated by the pharmacophore model (PhaM) defined using MCET. All the conformers in the series were aligned with the template to match with the enzyme in three dimensional (3D). The parameters of the enzyme at the interaction points were determined according to the descriptor of the molecules in the training set. Contour maps of enzyme parameters show the interaction points of aromatase with the flavonoid group used in this study. Traditional validation parameters (Q2 = 0.883 and R2pred = 0.895) were supported by a more stringent validation (a new parameter R2m-overall = 0.6).