1st International and 10th National Iranian Conference on Bioinformatics

2D QSAR model development for nitroimidazoles radiosensitizers DNA binding activity based on 2D and 3D descriptors

Paper ID : 1332-ICB10

Authors:

mostafa zakariazadeh¹, somaieh somaieh soltani *²

¹گروه زیست شناسی، دانشکده علوم، دانشگاه پیام نور، تهران، ایران

²گروه شیمی دارویی، دانشکده داروسازی، دانشگاه علوم پزشکی تبریز

Abstract:

Nitroimidazoles compounds have been used in cancer therapy as radiosensitizers [1]. They interact with DNA duplex structure via intercalating mode and change its conformer and interrupts its replication cycle [2]. To the prediction of their radiosensitization effectiveness (pC1.6), a linear model was developed based on 2D and 3D descriptors generated by PaDEL software [3]. 84 nitroimidazole compounds were divided into train (62 compounds) and test set (22 compounds). The 3D structures of compounds were prepared by Avogadro software and geometry optimized by MMFF94 force field. Descriptor selection was done using stepwise regression. Developed linear models were validated based on the internal and external validations. 9 descriptors were selected from 1875 calculated descriptors. Selected descriptors were AlogP, BCUTc1h, ASP4, MLFER_A, MLFER_E, TDB6s, TDB10s, MOMI-X, and RDF30m. The intercorrelatuon between selected descriptors were < 0.65. The correlatin coefficient between experimental and predicted pC1.6 were 0.77 for the external test set. Obtained results indicated a good prediction potency for the developed model in comparision to previous models [4]. The selected descriptors represented the importance of both 2-D and 3-D characteristics of nitroimidazoles in their effect on DNA duplex conformation change. The obtained data can be used for improve the effectiveness of studied compounds against cancer due to their binding to DNA.

Keywords:

QSAR; DNA-binding; nitroimidazole compounds, descriptor

Status : Paper Accepted (Poster Presentation)