N-Phenyl Ureidobenzenesulfonate derivatives as novel anticancer agents: QSAR and Molecular docking studies
Journal Title: Trends in Pharmaceutical Sciences - Year 2017, Vol 3, Issue 2
Abstract
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 block cell cycle progression in S-phase and induce DNA DSBs are discovered. Here, a set of PUB-SOs derivatives were applied to quantitative structural activity relationship (QSAR) analysis. A series of chemometric methods like MLR, FA- MLR, PCR and partial least squared included in variable selection genetic algorithm (GA-PLS), were used to relate structural features of these compounds with 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 protocols indicate that the main amino acids located in the active site cavity 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 B247and the most important base pairs inside the minor groove of DNA responsible for essential intercalation with DNA are G2, G4, G10, G12, A5, A6, C9 and C11.
Authors and Affiliations
Azar Mostoufi, Fariba Aliyan, Masood Fereidoonnezhad
Keywords
Related Articles
- EP ID EP339301
- DOI -
- Views 143
- Downloads 0
Valproic Acid-Induced Hepatotoxicity and the Protective Role of Thiol Reductants
Valproic acid (VPA) is a widely administered drug against epilepsy and several other neurological disorders. On the other hand, liver injury is a deleterious side effect associated with VPA. Oxidative stress seems to pl...
Cyproterone acetate-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs): preparation and optimization
Due to limited water solubility of cyproterone acetate and also limited skin permeation; lipid base nanocarriers with different size ranges were considered for topical delivery of cyproterone acetate. Lipid nanoparticles...
Analysis of the expression level of aquaporins under acetylene treatment and pathogen attack
Fusarium wilt disease and Sigatoka leaf spots threaten global market of Musa sp. Major Intrinsic Proteins (MIP) consisting aquaporins (AQPs) facilitate the transport of water and molecules like H2O2, CO2, silicon, boron,...
Molecular Docking and Thermodynamic Studies of the Interactions between Aspirinate Complexes of Transition metals and Cyclooxygenase-2 Enzyme: Quantum Chemical Calculations based on the ONIOM method
In the present research, molecular docking and thermodynamic properties of the transition metal complexes of aspirin were calculated against Cyclooxygenase-2 (COX-2) enzyme. Density functional theory with dispersion func...
Evaluation of Heavy Metals in Marinara chamomilla and lavandula angustifolia
Today soil and environmental pollution by heavy metals, has become a serious problem for human health. This pollution can be absorbed by agricultural products and enter the body. The purpose of this research is to invest...