Inflammatory bowel disease (IBD) is a complex autoimmune disease with dysfunction in pattern-recognition responses, including within the NLR family. Nucleotide-binding oligomerization domain, leucine rich repeat containing X1 (NLRX1) is a unique NLR with regulatory and anti-inflammatory functions resulting in protection from IBD in mouse models. NX-13 is an orally active, gutrestricted novel drug candidate that selectively targets and activates the NLRX1 pathway locally in the gut. In vitro and in vivo efficacy of NLRX1 activation by NX-13 was examined. Oral treatment with NX-13 alleviates disease severity, colonic leukocytic infiltration, and cytokine markers of inflammation in three mouse models of IBD (dextran sulfate sodium, Mdr1a 2/2 , and CD45RB hi adoptive transfer). Treatment of naive CD4 + T cells with NX-13 in vitro decreases differentiation into Th1 and Th17 subsets with increased oxidative phosphorylation and decreased NF-kB activation and reactive oxygen species. With stimulation by PMA/ionomycin, TNF-a, or H 2 O 2 , PBMCs from ulcerative colitis patients treated with NX-13 had decreased NF-kB activity, TNF-a + and IFN-g + CD4 + T cells and overall production of IL-6, MCP1, and IL-8. NX-13 activates NLRX1 to mediate a resistance to both inflammatory signaling and oxidative stress in mouse models and human primary cells from ulcerative colitis patients with effects on NF-kB activity and oxidative phosphorylation. NX-13 is a promising oral, gutrestricted NLRX1 agonist for treating IBD.

Polymorphism in drugs and bioactive molecules is not uncommon, and it has remained as one of the critical issues in drug development processes. While improving physicochemical properties of bioactive molecules has been a prime focus of the pharmaceutical chemists, not much efforts have been put toward the improvement of their potency via polymorphic modifications. Here, we consider five cases of 5-arylidene-2-aminothiazolidinones derivatives, the known anticancer agents, and discover eights polymorphs in three out of the five cases. We perform systematic crystallization experiments and detailed crystal structure analysis of the eight polymorphs and two compounds, estimate both their energetic and thermal stabilities, and compare their solid state properties. We also compare in-solution properties, e.g., equilibrium solubility, intrinsic dissolution rate, and phase stability, of three polymorphs of one of the cases. Further, we study the extent of inhibition imposed by those eight polymorphs and seven bulk and crystal forms of the compounds on the proliferation of MCF7 breast cancer cells and also the extent of their binding to the isozyme γ-enolase. Furthermore, we perform MD simulations on the eight polymorphs and one compound to estimate and compare their binding affinity with γ-enolase. Our experimental and MD simulation analyses in general emphasize the importance of polymorphism in improving the biological potency of individual molecules.

The first manganese-catalyzed cyclopropanation of indoles is reported in moderate to excellent yield with methyl-2-diazo-2-arylacetates. This new strategy involved acetyl (COCH3) as the directing group and exhibited exceptional functional group tolerance. In the absence of stereodirecting groups the desired products were obtained as a mixture of diastereomers (7:3 → 8:2). Control experiments and DFT studies elucidated the probable pathway for the formation of cyclopropane-fused indole product. Deacetylation of the final products afforded both C3-substituted NH-indoles.

Gardens are unaccomplished without the showy, pricey investments of ornamental plants. Ornamental plants, especially the flowering plants, have a significant impact on human life. They offer fresh air to the surroundings and release the negativity from the environment. Ornamental plants intrigued humans with their alluring odour and unique. Besides this, many ornamental plants have other economic uses other than just decoration or traditional customs which has been discussed. Many plants are edible and used in several kinds of beverages as medicinal values. Important domiciliary plants that belong to Asteraceae with both ornamental and therapeutic benefits are reviewed in this paper, namely, Calendula, Echinacea, Achillea, Acmella and Tanacetum. These plants possess a high nutritive value and can be cooked or consumed as salads. With numerous pharmaceutical ac-tivities of these plants, we hope that this review will bring awareness for their alternative use.

We report a novel blue LED mediated intramolecular C–H functionalization of tryptamine derivatives to generate azepino­[4, 5-b]­indoles (4) in moderate to good yields. By altering the substitution at the tryptamine nitrogen, intramolecular cyclopropanation is achieved in high yields under the same reactions condition to provide natural product inspired polycyclic indoles (6), which are further transformed to spiropiperidino (5 and 8) indoles in decent yields. The mechanism of formation of the compounds was investigated through DFT studies.