A newly synthesized 6-methyl-7H,8H,9H-[1,2,4]triazolo[4,3-b][1,2,4]triazepin-8-one for potential inhibitor of adenosine A1 receptor: a combined experimental and computational studies

Abstract

6-Methyl-7H,8H,9H-[1,2,4]triazolo[4,3-b][1,2,4]triazepin-8-onehas been synthesized, characterized by spectroscopic techniques (FT-IR, ¹H and ¹³C NMR) and finally the structure was confirmed by single crystal X-ray diffraction studies. In the title molecule, C₆H₇N₅O, the 7-membered ring adopts a bowl-like conformation. In the crystal, the molecules form stacks along the c-axis direction through offset π-stacking interactions between the 5-membered rings and C–H···N hydrogen bonds. The stacks are associated via a combination of N–H···N, C–H···O and C–H···N hydrogen bonds. Further, the Hirshfeld surface analysis reveals the nature of molecular interactions and the fingerprint plot provides information about the percentage contribution from each individual molecular contact to the surface. In addition, due to its biological interest the target molecule adenosine A1 receptor was found based on Structural Activity Relationship (SAR) analysis and, further, subjected into molecular docking and molecular dynamics analysis to understand the binding interaction and stability of the molecule in adenosine A1 receptor system. Furthermore, the Density Functional Theory (DFT) calculations were carried for free compound and the compound in active site (single point DFT), to know the internal stability.

Communicated by Ramaswamy H. Sarma     

Paraherbaspirillum soli gen. nov., sp. nov. isolated from soil

A bacterial strain, designated JS5-2^T, was isolated from soil collected from Jeju Island, Republic of Korea. The cells of the strain were Gram-negative, nonspore forming, catalase- and oxidase-positive, aerobic, nonmotile and rod-shaped. Strain JS5-2^T exhibited 96.2–97.2, 95.1–96.3, and 95.4–95.8% 16S rRNA gene sequence similarities to the genera Herbaspirillum, Oxalicibacterium, and Herminiimonas, respectively. The highest sequence similarities were with Herbaspirillum autotrophicum IAM 14942^T (97.2%) and Herbaspirillum frisingense GSF30^T (97.1%). The major fatty acids of strain JS5-2^T were C_16:0 (35.0%), C_17:0 cyclo (19.9%), C_18:1 ω7c (11.4%), and summed feature 3 (C_16:1 ω7c/C_15:0 iso 2-OH) (15.2%), and the major polar lipids of strain JS5-2^T were diphosphatidylglycerol and an unknown aminophospholipid. The strain contained Q-8 as the predominant ubiquinone. DNA-DNA relatedness values between strain JS5-2^T and H. autotrophicum IAM 14942^T, and H. frisingense GSF30^T were 32 and 35%, respectively. The DNA G+C content of strain JS5-2^T was 59.0 mol%. On the basis of phenotypic, genotypic, and physiological evidence, strain JS5-2^T represents a novel species of a new genus, for which the name Paraherbaspirillum soli gen. nov., sp. nov. is proposed. The type strain JS5-2^T (=KACC 12633^T =NBRC 106496^T) is proposed.     

Autophagy receptor CALCOCO2/NDP52 takes center stage in Crohn disease

To advance understanding of the complex genetics of Crohn disease (CD) we sequenced 42 whole exomes of patients with CD and five healthy control individuals, resulting in identification of a missense mutation in the autophagy receptor calcium binding and coiled-coil domain 2 (CALCOCO2/NDP52) gene. Protein domain modeling and functional studies highlight the potential role of this mutation in controlling NFKB signaling downstream of toll-like receptor (TLR) pathways. We summarize our recent findings and discuss the role of autophagy as a major modulator of proinflammatory signaling in the context of chronic inflammation.