Synthesis and molecular docking studies of novel pyrimidine derivatives as potential antibacterial agents

Molecular Diversity - The present work describes the in vitro antibacterial evaluation of some new pyrimidine derivatives. Twenty-two target compounds were designed, synthesized and preliminarily...     

Generalized fractional derivatives generated by a class of local proportional derivatives

Recently, Anderson and Ulness [Adv. Dyn. Syst. Appl. 10, 109 (2015)] utilized the concept of the proportional derivative controller to modify the conformable derivatives. In parallel to Anderson’s work, Caputo and Fabrizio [Progr. Fract. Differ. Appl. 1, 73 (2015)] introduced a fractional derivative with exponential kernel whose corresponding fractional integral does not have a semi-group property. Inspired by the above works and based on a special case of the proportional-derivative, we generate Caputo and Riemann-Liouville generalized proportional fractional derivatives involving exponential functions in their kernels. The advantage of the newly defined derivatives which makes them distinctive is that their corresponding proportional fractional integrals possess a semi-group property and they provide undeviating generalization to the existing Caputo and Riemann-Liouville fractional derivatives and integrals. The Laplace transform of the generalized proportional fractional derivatives and integrals are calculated and used to solve Cauchy linear fractional type problems.     

Introducing a novel class of four-component reactions

A novel four-component reaction approach to the efficient synthesis of triamide and amidodiester derivatives using amines or alcohols, aldehydes and alkyl or aryl isocyanides in the presence of Meldrum's acid as a CH acid, instead of carboxylic acid of Ugi four-component reaction, was studied.     

Design,synthesis and biological evaluation of novel flavone Mannich base derivatives as potential antibacterial agents

Molecular Diversity - A series of novel Mannich base derivatives of flavone containing benzylamine moiety was synthesized using the Mannich reaction. The results of antifungal activity are not...     

两种新型芴类衍生物的三光子吸收特性研究

研究了两种新型芴类衍生物9，9_二（2_乙基已基）_2，7_二咔唑_9H_芴（简记为DCZF）和9 ，9_二（2_乙基已基）_2，7_二（2_（4_甲氧基）苯_2，1_乙烯基）芴（简记为BMOSF）在N ，N_二甲基甲酰胺（DMF）中的线性吸收和单光子荧光行为，并用脉冲宽度为38ps，重复 频率为10 Hz的1064 nm Nd：YAG脉冲激光研究了两种化合物的三光子吸收性质.结果表明： 两种新材料的最大线性吸收峰分别位于330和380nm，吸收区域覆盖了270—420 nm波段. 两种化合物的荧光带位于蓝_紫区，中心波长为369和442 nm，都具有较小的斯托克斯位移. 化合物DCZF和BMOSF的三光子吸收系数分别为γ_DCZF=678×10^{- 20} cm3/W²和γ_BMOSF=592×10^-20 cm³/W². 同时， 两种新材料还表现出明显的三光子吸收光限幅效应，当入射光强分别为8和6GW/cm²时，非线性透过率分别达到30%和45%. 关键词： 芴类衍生物 三光子吸收 光限幅 非线性透过率     

One-pot multi-component synthesis of novel chromeno[4,3-b]pyrrol-3-yl derivatives as alpha-glucosidase inhibitors

Molecular Diversity - A green and efficient one-pot multi-component protocol was developed for the synthesis of some novel dihydrochromeno[4,3-b]pyrrol-3-yl derivatives through the reaction of...     

Synthesis of novel fluorinated bis(biphenyl)diacetylene derivatives as highly birefringent nematic liquid crystalline materials

Three novel fluorinated bis(biphenyl)diacetylene (1,4-bis(biphenyl-4-yl)buta-1,3-diyne) derivatives, with alkoxy tails at the terminal positions, were prepared for use as high-birefringent nematic materials. To lower the thermal transition temperatures and determine the origin of the nematic phase of these compounds, fluorine atoms were introduced at lateral positions. Thermal transition temperatures and mesomorphic properties were investigated by differential scanning calorimetry and polarized optical microscopy. In addition, birefringence was measured using a microscopic method based on the interference method. Both the nematogenic properties and optical performances depended not only on the number of fluorine substituents, but also on the position of the substituents. The compound having the highest fluorine content exhibited the lowest birefringence, and the compound bearing fluorine atoms only on the inner benzene rings of the biphenyl cores exhibited an enantiotropic nematic phase with a maximum birefringence value of 0.48 at 550 nm and 140 °C.     

Synthesis and biological evaluation of novel SIPI-7623 derivatives as farnesoid X receptor (FXR) antagonists

Most of reported steroidal FXR antagonists are restricted due to low potency. We described the design and synthesis of novel nonsteroidal scaffold SIPI-7623 derivatives as FXR antagonists. The most potent compound A-11 (IC₅₀?=?7.8?±?1.1 μM) showed better activity compared to SIPI-7623 (IC₅₀?=?40.8?±?1.7 μM) and guggulsterone (IC₅₀?=?45.9?±?1.1 μM). Docking of A-11 in FXR’s ligand-binding domain was also studied.

     

Identification of Tmem10/Opalin as a novel marker for oligodendrocytes using gene expression profiling

Background  

During the development of the central nervous system, oligodendrocytes generate large amounts of myelin, a multilayered insulating membrane that ensheathes axons, thereby allowing the fast conduction of the action potential and maintaining axonal integrity. Differentiation of oligodendrocytes to myelin-forming cells requires the downregulation of RhoA GTPase activity.     

Synthesis and biological evaluation of benzomorpholine derivatives as novel EZH2 inhibitors for anti-non-small cell lung cancer activity

The histone lysine methyltransferase EZH2 has been reported to play important roles in cancer aggressiveness, metastasis and poor prognosis. In this study, a series of benzomorpholine derivatives were synthesized and biologically evaluated as EZH2 inhibitors. The target compounds were obtained in good yields from 3-amino-5-bromo-2-hydroxybenzoic acid via cyclization, Suzuki coupling and amidation as the key steps. A preliminary optimization study led to the discovery of several potent novel EZH2 inhibitors (6b, 6c, 6x and 6y). Moreover, 6y inhibited the A549 and NCI-H1975 cell lines (IC₅₀?=?1.1 µM and 1.1 µM, respectively). Further studies indicated that 6y can reduce EZH2 expression in intact cells and cause cell arrest in the G2/M phase.

     

Green synthesis and characterization of novel 1,2,4,5-tetrasubstituted imidazole derivatives with eco-friendly red brick clay as efficacious catalyst

Use of cheaper and recyclable materials contributes positively to economic growth with environmental sustainability. We report the prospect of utilizing red brick clay as catalyst, which exhibited excellent activity in rapid one-pot four-component condensation of 1,2,4,5-tetrasubstituted imidazoles with high conversion and yields (91–96%) in aqueous medium at 60 °C in short reaction times (25–40 min). The red brick clay material was fully characterized by XRD, FT-IR, SEM, TEM, EDX and BET analyses. Red brick clay consisted of oxides of Si (20.38%), Fe (19.55%), Al (14.30%) and minor amounts of Ca (3.60%) and Mg (1.68%). The slate-like-shaped structure morphology and flaky appearance of inexpensive solid clay material proved competent material for the synthesis of 15 novel 1,2,4,5-tetrasubstituted imidazole derivatives. In addition, the advantages of the eco-friendly method are non-toxicity and re-usability of the catalyst. Reaction offers 78% atom economy and 84% carbon capture.

     

Ultrasound-promoted synthesis and immunosuppressive activity of novel quinazoline derivatives

An environmentally friendly and mild Bischler cyclization was developed to access quinazolines with diverse substitution. Based on this method, a library of 53 quinazoline derivatives was prepared and tested in vitro for cytotoxicity and inhibition on T-cell and B-cell proliferation. Compounds 6b, 7b, 17b, 33, and 35 showed higher inhibitory activity on both T-cell and B-cell proliferations, with IC(50) values of 6.16, 6.30, 5.43, 2.54, and 9.80?μM on T-cell, respectively. All the tested compounds showed no obvious cytotoxicity at 10?μM concentration. The preliminary structure-activity relationship was concluded revealing that 4-position is the key modification site for potent quinazoline immunosuppressive agent.     

Design,synthesis, in silico and in vitro evaluation of novel diphenyl ether derivatives as potential antitubercular agents

Molecular Diversity - Diphenyl ether derivatives inhibit mycobacterial cell wall synthesis by inhibiting an enzyme, enoyl-acyl carrier protein reductase (InhA), which catalyses the last step in the...     

Identification of an optimal derivatives approximation by variational data assimilation

Variational data assimilation technique applied to identification of optimal approximations of derivatives near boundary is discussed in frames of one-dimensional wave equation. Simplicity of the equation and of its numerical scheme allows us to discuss in detail as the development of the adjoint model and assimilation results. It is shown what kind of errors can be corrected by this control and how these errors are corrected. This study is carried out in view of using this control to identify optimal numerical schemes in coastal regions of ocean models.     

Synthesis and properties of novel blue-emitting materials:anthracene-based derivatives

Two kinds of novel blue-emitting materials, anthracene-based derivatives, are synthesized by the Suzuki coupling reaction. It is worth noting that the maximum emission wavelengths of the two materials are 441 and444 nm in tetrahydrofuran and 456 and 454 nm in film states, which are the typical blue fluorescence and the fluorescence quantum yields of them are 0.87 and 1.12 by using 9,10-diphenylanthracene eΦf=0.90 T as a calibration standard. The full width at half maximum of them are 56, 55 nm in solution, respectively, presenting good color purity. Both of them display superior thermal properties and electrochemical properties.Scanning electronic microscope results show that the films of two compounds are continuous, compact, and smooth after 100°C for 3 h. These data indicate their potential to be prepared for high efficiency and long operation lifetime organic light-emitting diodes devices.     

Identification of novel Interleukin-2 inhibitors through computational approaches

Interleukin-2 (IL-2), is a 15.5-kDa cytokine that is now emerging as a target in drug discovery for novel therapeutic approaches in several autoimmune disorders. In an attempt to identify new inhibitors for the IL-2/IL-2R interaction, virtual screening (VS) was performed. Four different docking programs (GOLD, FlexX, Glide, and LigandFit) in combination with several scoring functions were used to identify novel IL-2/IL-2R interaction inhibitors. VS of a database of 6,000 compounds resulted in the identification of three novel and moderately active hits with IC $_{50}$ values ranging from 6.6 to 44.3  $\upmu $ M. Furthermore, the effect of these three compounds on the expression of IL-2R $\alpha $ was assessed. The three active hits showed dose-dependent inhibitory effects on the expression of IL-2R $\alpha $ with an IC $_{50}$ range of 5.8 to 140  $\upmu $ M. The cytotoxicity of these active hits was assessed using three normal cell-lines: bovine kidney cell-line (MDBK), mouse fibroblast cell-line (3T3), and rat hepatocytes cell-line (CC-1). The compounds were found to have negligible cytotoxicity compared to their IC $_{50}$ as IL-2/IL-2R interaction inhibitors. These results demonstrate that our VS protocol can identify novel inhibitors for IL-2/IL-2R interaction that effectively suppress IL-2 production, as well as the expression of IL-2R $\alpha $ . Optimization of these molecules could lead to improved and effective anti-inflammatory therapeutics.     

Synthesis and anticholinesterase activity of novel non-hepatotoxic naphthyridine-11-amine derivatives

Molecular Diversity - In the present study, 14 novel naphthyridine-11-amine derivatives were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase...