56894-92-9Relevant academic research and scientific papers
Antimicrobial activity and SAR study of new gemini imidazolium-based chlorides
Pa?kowski, ?ukasz,B?aszczyński, Jerzy,Skrzypczak, Andrzej,B?aszczak, Jan,Kozakowska, Karolina,Wróblewska, Joanna,Kozuszko, Sylwia,Gospodarek, Eugenia,Krysiński, Jerzy,S?owiński, Roman
, p. 278 - 288 (2014/03/21)
A series of 70 new 3,3′(α,ω-dioxaalkyl)bis(1- alkylimidazolium) chlorides were synthesized. They were characterized with respect to surface active properties and antimicrobial activity against the following pathogens: Staphylococcus aureus, Enterococcus faecalis, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Candida krusei, and Candida albicans. In this article, besides description of the synthesis, we characterize a set of features of these compounds, concerning their structure (described by the length of the dioxaalkan spacer and the length of the alkyl substituent in the aromatic ring) and surface active properties (critical micelle concentration, value of surface tension at critical micelle concentration, value of surface excess, molecular area of a single particle, and free energy of adsorption of molecule). Then, we present a SAR study for Staphylococcus aureus, as one of the most widespread pathogenic strains, conducted with the help of the Dominance-based Rough Set Approach (DRSA), that involves identification of relevant features and relevant combinations of features being in strong relationship with a high antimicrobial activity of the compounds. The SAR study shows, moreover, that the antimicrobial activity is dependent on the type of substituents and their position at the chloride moiety, as well as on the surface active properties of the compounds.
Design, synthesis and biological characterization of novel inhibitors of CD38
Dong, Min,Si, Yuan-Qi,Sun, Shuang-Yong,Pu, Xiao-Ping,Yang, Zhen-Jun,Zhang, Liang-Ren,Zhang, Li-He,Leung, Fung Ping,Lam, Connie Mo Ching.,Kwong, Anna Ka Yee,Yue, Jianbo,Zhou, Yeyun,Kriksunov, Irina A.,Hao, Quan,Cheung Lee, Hon
scheme or table, p. 3246 - 3257 (2011/06/10)
Human CD38 is a novel multi-functional protein that acts not only as an antigen for B-lymphocyte activation, but also as an enzyme catalyzing the synthesis of a Ca2+ messenger molecule, cyclic ADP-ribose, from NAD+. It is well established that this novel Ca2+ signaling enzyme is responsible for regulating a wide range of physiological functions. Based on the crystal structure of the CD38/NAD+ complex, we synthesized a series of simplified N-substituted nicotinamide derivatives (Compound1-14). A number of these compounds exhibited moderate inhibition of the NAD+ utilizing activity of CD38, with Compound4 showing the highest potency. The crystal structure of CD38/Compound4 complex and computer simulation of Compound7 docking to CD38 show a significant role of the nicotinamide moiety and the distal aromatic group of the compounds for substrate recognition by the active site of CD38. Biologically, we showed that both Compounds4 and 7 effectively relaxed the agonist-induced contraction of muscle preparations from rats and guinea pigs. This study is a rational design of inhibitors for CD38 that exhibit important physiological effects, and can serve as a model for future drug development.
