Binding Mechanism and Molecular Design of Benzimidazole/Benzothiazole Derivatives as Potent Abl T3151 Mutant Inhibitors

Despite the efficacy of imatinib therapy in chronic myelogenous leukemia, the development of drug-resistant Abl mutants, especially the most difficult overcoming T3151 mutant, makes the search for new Abl T3151 inhibitors a very interesting challenge in medicinal chem- istry. In this work, a multistep computational framework combining the three dimensional quantitative structure-activity relationship （3D-QSAR）, molecular docking, molecular dy- namics （MD） simulation and binding free energy calculation, was performed to explore the structural requirements for the Abl T315I activities of benzimidazole/benzothiazole derivatives and the binding mechanism between the inhibitors and Abl T315I. The established 3D-QSAR models exhibited satisfactory internal and external predictability. Docking study elucidated the comformations of compounds and the key amino acid residues at the binding pocket, which were confirmed by MD simulation. The binding free energies correlated well with the experimental activities. The MM-GBSA energy decomposition revealed that the van der Waals interaction was the major driving force for the interaction between the ligands and Abl T3151. The hydrogen bond interactions between the inhibitors and Met318 also played an important role in stablizing the binding of compounds to Abl T315I. Finally, four new compounds with rather high Abl T3151 activities were designed and presented to experimenters for reference.

Second-order Nonlinear Optical Properties of a Series of Benzothiazole Derivatives

The second-order nonlinear optical (NLO) properties of a series of benzothiazole derivatives were studied by use of the ZINDO-SOS method. These chromophores are formed by a donor-π-bridge-acceptor system, based on a nitro group connected with benzothiazole as the acceptor and a hydroxyl-functional amino group as the donor. For the purpose of comparison, we also designed molecules in which nitrobenzene is an acceptor. The calculation results indicate that benzothiazole derivatives exhibit larger second-order polarizabilities than nitrobenzene derivatives. In order to clarify the origin of the NLO response of these chromophores, their electron properties were investigated as well. The benzothiazole derivatives are good candidates for application in electro-optical device due to their high optical nonlinearities, good thermal and photonic stability.

Synthesis of Two Novel Additives and Study of Their Tribological Properties in Rapeseed Oil

Two novel ashless additives - benzothiazole derivatives containing boron and chlorine, OBC and BBC, were synthesized. The tribological performances of OBC and BBC at different mass ratios as additives in rapeseed oil （RO） were examined on a four-ball machine. The worn surfaces of the lower steel balls lubricated by oil samples were analyzed by means of scanning electron microscopy （SEM）. The test results showed that OBC and BBC had good solubility in the base oil, and could effectively increase the load-carrying capacity of the base oil. The maximum non-seizure load of oil sample containing 1.5 m% BBC was 1117 N, which was 2.3 times as much as that of the base oil. Both OBC and BBC could improve the anti-wear and corrosion inhibiting performance and thermal stability of the base oil, whose initial decomposition temperatures was above 350 ~C. However, OBC and BBC at different concentrations could increase the friction coefficient of the base oil. The SEM morphology of steel balls lubricated by oil samples containing 1.5 m% additives seemed to be more uniform and smoother than that of the base oil, and the scars formed were very shallow.

Single & Two-photon Excited Fluorescence of Two New Compounds with 2-Benzothiazolyl as Electron Acceptor

Two new D--A type compounds, where electron-donor D is tertiary amino group, electron-acceptor A is 2-benzothiazolyl and ?is two conjugated styryl units, have been synthesized. They are named as trans, trans-2-{4-[4-(N, N-diethylamino)styryl]styryl}-1, 3-benzothiazole and trans, trans-2-{4-[4-(N, N-diphenylamino)styryl]styryl}-1, 3-benzothiazole. Both compounds show strong two-photon excited fluorescence in yellow-orange region when excited by a femtosecond laser at 800 nm.