N-Phenyl Ureidobenzenesulfonate derivatives as novel anticancer agents: QSAR and Molecular docking studies

DNA double strand-breaks (DSBs) are the most deleterious lesions that can affect the genome of living beings and are lethal if not quickly and properly repaired. Recently, N-phenyl ureidobenzenesulfonates (PUB-SOs) as tubulin inhibitors that are blocking the cells cycle progression in S-phase and inducing DNA DSBs is discovered. Here, a set of PUB-SOs derivatives were applied to quantitative structural activity relationship (QSAR) analysis. A series of chemometrics methods like MLR, FA- MLR, PCR and partial least squared included in variable selection genetic algorithm (GA-PLS) were used for relations between structural features of these compounds and their anti-proliferative activity against MCF-7 cell line. New potent lead compounds were also designed based on new structural patterns using in silico-screening study. Molecular docking studies of these compounds on DNA and tubulin were conducted. The results obtained from validated docking protocol indicate that the important amino acids inside the active site cavity that are in charge of essential interactions with tubulin are Ala30, Lys B254, Asn B258, Met B259, Asn A101, Glu A183, Thr A179, Leu B255, Ser A178 and Gln B247. And the most important base pairs inside the minor groove of DNA being responsible for essential interclation with DNA are G2, G4, G10, G12, A5, A6, C9 and C11 base pairs. 

Keywords:

QSAR , molecular docking , N-phenyl ureidobenzenesulfonates , in silico-screening