A novel series of indolyl oxoacetamide-quinazolinone hybrid analogues (9aa–9df) were designed, synthesized, and evaluated for their in vitro pancreatic lipase (PL) inhibitory potential that may lead to efficient anti-obesity agents.

In view of the ethno medicinal use of Enhydra fluctuans for the treatment of kidney stones; the present study aimed to elucidate the molecular mechanisms involved in the amelioration of nephrolithiasis through a network pharmacology approach. The phytoconstituents were queried in DIGEP-Pred to identify the regulated proteins. The modulated proteins were then enriched in the STRING to predict the protein-protein interactions and the probably regulated pathways were traced in the Kyoto Encyclopedia of Genes and Genomes. Further, the network was constructed using Cytoscape ver 3.5.1. Results showed that β-carotene was found to be regulating maximum targets i.e. 26. In addition, 63 proteins were triggered by the components in which the vitamin D receptor was targeted by the maximum phytoconstituents i.e. 16. The enrichment analysis identified the regulation of 67 pathways in which fluid shear stress and atherosclerosis-associated pathways (KEGG entry hsa05418) regulated ten genes. Further, protein kinase C-α was traced in 23 different pathways. In addition, the majority of the regulated genes were identified from the extracellular space via the modulation of 43 genes. Also, nuclear receptor activity had the maximum molecular function via the regulation of 7 genes. Likewise, the response to organic substance was predicted to trigger the top genes i.e. 43. In contrast, Stigmasterol, Baicalein-7-o-glucoside, and Kauran-16-ol were found to have a high affinity to bind with the VDR receptor confirmed by the molecular modelling and the dynamics. Hence, the study elucidated the probable molecular mechanisms of E. fluctuans in managing nephrolithiasis and identified the lead molecules, their targets, and possible pathways. Communicated by Ramaswamy H. Sarma

The decoction of the whole plant of Enhydra fluctuans is used ethno medicinally by various tribes for the treatment of kidney stones and urinary problems. However, no scientific studies were carried out to delineate its influence on urinary stone formation and crystallisation. Hence, the present study is proposed to investigate the effect of the aqueous extract of Enhydra fluctuans extract on in vitro crystallisation of calcium oxalate. The present study also evaluated. in silico studies of the metabolites with the target proteins present in the renal calcium oxalate stone matrix. The plant material was subjected to decoction to obtain an aqueous extract. The effect of the extract on calcium oxalate crystallization was evaluated by in vitro nucleation and aggregation assays. Further, the metabolites present in E. fluctuans were mined from the existing literature and their number was found to be 35. The selected 35 metabolites of E. fluctuans were subjected to molecular docking with the 5 proteins which are known to be responsible for calcium oxalate crystal growth. Results of in vitro studies indicated that the extract (50, 100, and 200 μg/mL) and standard drug cystone (1,000 μg/mL) exhibited an inhibitory role in the nucleation process where the percentage inhibitions were 52.69, 43.47, 21.98, and 31.67 μg/mL respectively. The results of molecular docking studies revealed that 2 out of 35 metabolites i.e. Baicalein-7-O-diglucoside and 4′,5,6,7-Tetrahydroxy-8-methoxy isoflavone-7-O-beta-D- galactopyranosyl-(1→3)-O-beta-D-xylopyranosyl-(1→4)- O-alpha-L-rhamnopyranoside showed modulatory effects on the four renal stone matrix-associated protein (Human CTP: Phosphoethanolamine Cytidylyltransferase (Protein Data Bank ID: 3ELB), UDP glucose: glycoprotein glucosyltransferase 2 (Gene: UGGT2) (AlphaFold) and RIMS-binding protein 3A (Gene: RIMBP3) (AlphaFold), and Ras GTPase activating-like protein (PDB: 3FAY) based on their docking scores which indicates that they may inhibit the crystallization process. Findings from this study show that Enhydra fluctuans may be effective in the prevention of the crystallization of calcium oxalate. However, further, in vivo studies as well as molecular studies are needed to be conducted to confirm and strengthen its anti-urolithiatic activity and to elucidate the possible mechanism of action involved therein.

RNA structural motifs can serve as recognition sites for proteins or regulatory elements. Notably, these specific RNA shapes are directly related to many diseases. Targeting specific RNA motifs using small molecules is an emerging domain of study within the area of drug discovery. Targeted degradation strategies are a relatively modern technology in drug discovery, with important clinical and therapeutic outcomes. These approaches involve using small molecules to selectively degrade specific biomacromolecules associated with a disease."Ribonuclease-Targeting Chimeras" (RiboTaCs) represent a promising type of targeted degradation strategy because of their ability to selectively degrade structured RNA targets. In this review, the authors present the evolution of RiboTaCs, their underlying mechanism, and their in-vitro validation. The authors summarize several disease-associated RNAs that have been previously targeted for degradation using the RiboTaC strategy and discuss how their degradation led to alleviating disease-associated phenotypes in-vitro and in-vivo. There are several future obstacles that still need to be overcome for RiboTaC technology to fully realize its potential. Despite these challenges, the authors are optimistic about its prospects, which have the potential to fundamentally transform the treatment of a wide range of diseases.