Structure-activity relationship of N-benzenesulfonyl matrinic acid derivatives as a novel class of coxsackievirus B3 inhibitors.

A novel series of N-benzenesulfonyl matrinic amine/amide and matrinic methyl ether analogues were designed, synthesized and evaluated for their in vitro anti-coxsackievirus B3 (CVB3) activities. The structure-activity relationship (SAR) studies revealed that introduction of a suitable amide substituent on position 4' could greatly enhance the antivirus potency. Compared to the lead compounds, the newly synthesized matrinic amide derivatives 21c-d and 21j exhibited stronger anti-CVB3 activities with lower micromolar IC50 from 2.5 µM to 2.7 µM, and better therapeutic properties with improved selectivity index (SI) from 63 to 67. The SAR results provided powerful information for further strategic optimization, and these top compounds were selected for the next evaluation as novel enterovirus inhibitors.

[XPS and UPS characterization for Cr and Mn in high-temperature oxide films of bulk nanocrystalline 304 stainless steel].

The authors studied the binding energies of valence electrons of two oxide scales, the atomic percentages of Cr and Mn elements in two oxide films, the work function of two oxide films on bulk nanocrystalline 304 stainless steel (BN-SS304) and conventional polycrystalline 304 stainless steel (CP-SS304). BN-SS304 was prepared by severe rolling technique, and the two oxide films were formed in atmosphere at 900 degrees C for 24 hours oxidation on BN-SS304 and CP-SS304 surfaces. In the two oxide films, Cr and Mn elements exist in the forms of Cr3+, Cr0, Mn4+ and Mn0. The atomic percentage ratios of Cr+ / (Cr3+ + Cr0) and Mn4+ / (Mn4+ + Mn0) in the oxide film on BN-SS304 are lower than those in the oxide film on CP-SS304. The interactions of the two oxides and the valence electrons of elements are Mn-O, Cr-O,3d and 4s of Mn0 and Cr0. The binding energies of the valence electrons in the oxide film on BN-SS304 are larger than those in the oxide film on CP-SS304, the work function of the oxide film on BN-SS304 is 0.07 eV larger than that on CP-SS304.

Synthesis and evaluation of halogenated 12N-sulfonyl matrinic butanes as potential anti-coxsackievirus agents.

Twenty-eight new 12N-benzenesulfonyl matrinic butane and halogenated 12N-sulfonyl matrinic butane/ethane derivatives were designed, synthesized and evaluated for their anti-coxsakievirus activities against CVB3 taking compound 1 as the lead. SAR analysis indicated the introduction of a fluoro atom on the 1'-position might be helpful for keeping potency. Among them, compound 8a exhibited potential activities against all CVBs with IC50 ranging from 0.69 to 5.14 µM, suggesting a broad-spectrum anti-coxsackievirus B feature. In addition, it also displayed an excellent PK and a good safety profile, indicating a highly druggable nature. Thus, we consider compound 8a to be a promising drug candidate in the treatment of not only viral myocarditis caused by CVB3 but also various diseases infected with coxsackieviruses B.