Design,synthesis, molecular docking,and spectral studies of new class of carbazolyl polyhydroquinoline derivatives as promising antibacterial agents with noncytotoxicity towards human mononuclear cells from peripheral blood

In the present study, we report the design and eco-benign synthesis of new class of carbazolyl-1,4-dihydropyridine (1,4-CDHP) and carbazolyl-1,8-dioxodecahydroacridine (CAD) derivatives via a three-component coupling reaction of substituted carbazole aldehydes, ethyl acetoacetate/dimedone, and ammonium acetate under solvent-free conditions at 112°C to 115°C. We also report an efficient one-pot synthesis of new class of carbazolyl polyhydroquinoline (CPQ) derivatives via a four-component coupling reaction of substituted ethyl acetoacetate, dimedone, ammonium acetate, and carbazole aldehydes in acetonitrile/water medium (3:1) at 73°C to 75°C in moderate yields. All the products were thoroughly characterized by ¹H NMR, ¹³C NMR, Fourier transform infrared (FTIR), mass spectral, and CHN analysis. The synthesized heterocyclic compounds were evaluated for their in vitro antibacterial activity against pathogenic strains of both Gram-negative and Gram-positive bacteria. Minimum inhibitory concentration (MIC) of the active compounds was evaluated by macrodilution method. The CPQ derivative ( 8a ) displayed superior antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhi with the MIC values of 16.0 to 32.0 μg/mL in comparison with the reference drug. The mechanism of antibacterial action of the CPQ derivatives was investigated via scanning electron microscope (SEM) studies. The molecular docking studies indicate that the CPQ derivative ( 8a ) binds to the cell wall protein of E coli and P aeruginosa by formation of hydrogen bonds with amino acid residues (TYR328 and GLU249) of the bacterial cell wall protein. The 1,4-CDHP, CAD, and CPQ derivatives were either noncytotoxic or exhibited minimal cytotoxicity towards human mononuclear cells from peripheral blood. All the products were evaluated for Lipinski rule of five (RO5) and were found to have good oral bioavailability.     

Implementing modular adaptation of scientific software

Scientific software often needs to be adapted for different execution environments, problem sets, and available resources to ensure its efficiency and reliability. However, for existing programs, implementing adaptations by directly modifying source code can be time-consuming, error-prone, and difficult to manage for today's complex software. In this paper, we present a modular approach to realizing adaptation for existing scientific codes. By treating adaptation as a separate concern, our approach supports the development of application-specific, context-aware adaptation schemes without directly modifying the original code. Our approach uses a compositional framework that offers language-neutral mechanisms to integrate separately written adaptation code with existing code. Using our approach, scientific programmers can focus on the design and implementation of adaptation schemes separately from the original code development, and then compose an adaptive application whose original capabilities are enhanced in diverse aspects such as performance and stability. Our compositional approach enables fine-grained adaptation, so that an application's program behavior is controlled at the function or algorithm level by adaptation code plugged into the application. By applying our approach to real-world scientific applications to implement various adaptation scenarios, we demonstrate applicability and effectiveness for adapting scientific software.     

Alkyloxy azo-cinnamate ester based thermotropic liquid crystals and their photophysical investigations

Two series of rod shaped Schiff base containing azo-cinnamate thermotropic liquid crystalline compounds were synthesized and characterized. These molecules have four different alkyl spacers (n = 6, 8, 10, and 12) at one end and a dodecyloxy chain at another end (n = 12) which influence their liquid crystalline properties. Liquid crystallinity commence from six methylene spacer onwards in the series exhibiting with Nematic to Smectic-C mesophases. Analytical data confirm the molecular structures of homologues series of compounds. The characteristic texture of liquid crystalline phases obtained using polarizing‐light microscope with a heating stage. The structural transformation of these liquid crystals was confirmed by differential scanning calorimetry. All the compounds exhibited various calamitic mesophases with wide mesomorphic temperature ranges. The relationship between structure and mesomorphic properties was discussed in framework of geometrical configuration of central unit, linking part, and length of alkoxy chains. Photosensitive azobenzene group undergoes photoisomerization under UV light and monitored by UV-Visible spectroscopy.