A study on MAPK/ERK and CDK2-Cyclin-E signal switch "on and off" in cell proliferation by bis urea derivatives of 1, 4-Diisocyanatobenzene.

A series of novel substituted bisurea 1,4-Diisocyanatobenzene compounds were designed, synthesized and introduced as potent anticancer compounds and screened for their in vitro anti-proliferative activities in human cancer cell lines. The structures of all titled compounds were characterized using Fourier-transform infrared mass spectra, nuclear magnetic resonance spectroscopy, elemental analysis and evaluated their sustainability using biological experiments. A selected group of ten derivatives were apprised for their anti-proliferative activity. The compounds 3d and 3e displayed potent anticancer activity with low IC50 value of 5.40, and 5.89 µM against HeLa cancer cell lines. The observed apoptosis data has demonstrated that compounds 3d and 3e induce the activaties of caspase-9 and caspase-3, the compounds 3d and 3e regulated fungal zone inhibition. Due to promising growth inhibitions, the all synthesized compounds were allowed to campaign includes quantum-polarized-ligand, quantum mechanical and molecular mechanical, docking experiments. The compounds 3d and 3e have exhibited a higher affinity for ERK/MAP kinase and CDK2 proteins. The molecular docking interactions have demonstrated two stage inhibition of cancer cells by binding with ERK/MAP kinase and CDK2 leads to inactivation of cell proliferation,cell cycle progression,cell divisionanddifferentiation, and hypo-phosphorylation of ribosome leading cells to restricts at point boundary of the G1/S phase. The long-range molecular dynamics, 150 ns, simulations were also revealed more consistency by 3d. Our study conclude good binding propensity for active-tunnel of ERK/MAP kinase and CDK2 proteins, by 3d (1,1'-(1,4-phenylene) bis(3-(2-chlorobenzyl)urea)), to suggest that the designed and synthesized 3d is to use as selective novel nuclei in anti-cancer chemotherapeutics.

Design, synthesis, anti-tobacco mosaic viral and molecule docking simulations of urea/thiourea derivatives of 2-(piperazine-1-yl)-pyrimidine and 1-(4-Fluoro/4-Chloro phenyl)-piperazine and 1-(4-Chloro phenyl)-piperazine - A study.

The objectives of the present work are to design, syhthesize and introduce novel urea/thiourea derivatives of 2-(piperazine-1-yl)-pyrimidine and 1-(4-Fluoro/4-Chloro phenyl)-piperazine molecules as tobacco mosaic virus (TMV) inhibitors. A series of urea/thiourea derivatives containing pyrimidine and piperazine moieties were synthesized, characterized using Fourier-transform infrared (FTIR) mass spectra, nuclear magnetic resonance (NMR) spectroscopy, elemental analysis and evaluated their sustainability using biological experiments. The anti-viral bioassay of the title compounds showed an antiviral activity against TMV. The compounds synthesized, 9j, 6g and 3d, showed highly-potential curative, protective, and inhibitory activities against TMV at 500 mg/mL formulation. All these compounds were allowed to quantum-polarized-ligand (quantum mechanical and molecular mechanical (QM/MM)) docking experiments. The compounds 9j, 6g and 3d structurally exhibited identical higher affinity towards TMV-Helicase and TMV-Coat proteins. The docking interactions proposed had two stage inhibition of TMV virus by binding to coat protein and helicase for inhibition of RNA replication. The long-range molecular dynamics (150 ns) simulations has revealed more consistency by 9j, 6g and 3d. The present study outcomes good binding propensity for active-tunnel of TMV-Hel enzyme, by these thiourea, urea derivatives, 9j, 6g and 3d, to suggest that the designed and synthesized were ideal for proposing as selective novel inhibitors to target for TMV.