Tandem Reactions of Electrophilic Indoles toward Indolizines and Their Subsequent Transformations through Pd(II)-Mediated C-H Functionalization to Access Polyring-Fused N-Heterocycles.

A simple and efficient synthetic approach for generating a library of structurally novel indolizines has been developed via sequential 1,3-dipolar cycloaddition-ring opening processes. Using this methodology, a series of indolizines bearing different substituents were made in moderate to good yields. The presence of two functionalizable C-H bonds in these indolizine motifs makes them attractive for accessing fused indolizine scaffolds. In this line, we have introduced palladium-mediated site-selective C-H functionalizations, where the N-center and the two C-H centers of the indolizine moiety can be readily functionalized to generate fused N-heterocycles. Utilizing a Pd-mediated dual C-H activation of 5-benzoyl-substituted indolizine afforded 6H-indeno-indolizine, and a tetracene, viz., indolizino[2,1-b]indoles, was produced in the same substrate by the Pd-catalyzed selective C-H amination in the presence of oxygen.

Single Nucleotide Polymorphisms [SNPs] in the Shadows: Uncovering their Function in Non-Coding Region of Esophageal Cancer.

Esophageal cancer is a complex disease influenced by genetic and environmental factors. Single nucleotide polymorphisms [SNPs] in non-coding regions of the genome have emerged as crucial contributors to esophageal cancer susceptibility. This review provides a comprehensive overview of the role of SNPs in non-coding regions and their association with esophageal cancer. The accumulation of SNPs in the genome has been implicated in esophageal cancer risk. Various studies have identified specific locations in the genome where SNPs are more likely to occur, suggesting a location-specific response. Chromatin conformational studies have shed light on the localization of SNPs and their impact on gene transcription, posttranscriptional modifications, gene expression regulation, and histone modification. Furthermore, miRNA-related SNPs have been found to play a significant role in esophageal squamous cell carcinoma [ESCC]. These SNPs can affect miRNA binding sites, thereby altering target gene regulation and contributing to ESCC development. Additionally, the risk of ESCC has been linked to base excision repair, suggesting that SNPs in this pathway may influence disease susceptibility. Somatic DNA segment alterations and modified expression quantitative trait loci [eQTL] have also been associated with ESCC. These alterations can lead to disrupted gene expression and cellular processes, ultimately contributing to cancer development and progression. Moreover, SNPs have been found to be associated with the long non-coding RNA HOTAIR, which plays a crucial role in ESCC pathogenesis. This review concludes with a discussion of the current and future perspectives in the field of SNPs in non-coding regions and their relevance to esophageal cancer. Understanding the functional implications of these SNPs may lead to the identification of novel therapeutic targets and the development of personalized approaches for esophageal cancer prevention and treatment.

Development of Mangifera indica leaf extract incorporated carbopol hydrogel and its antibacterial efficacy against Staphylococcus aureus.

Staphylococcus aureus is a major pathogen causing skin infections and currently treated with topical antibiotic preparations like bacitracin, triple antibiotic ointment (neomycin, polymixin B, and bacitracin), gentamicin or mupirocin. However, their efficacies are restricted when the infections are caused by drug resistant strains. There is an imperative need for new antibacterial compounds for the management of S. aureus topical infections. Maginfera indica (mango) is reported for its antibacterial efficacy in many traditional plant based medicines. In this study we tested the antibacterial efficacy of the methanol extract of mango leaf against SA113 and S. aureus clinical strains. Mango leaf extract (MLE) was found to be an effective anti-staphylococcal agent, non-mutagenic, and contains phytochemicals such as tannins, saponins, flavanoids, phenols, and coumarins. Further, the mango leaf extract (from stock MLE concentration of 130 mg/ml) containing carbopol hydrogel (MLEC) was prepared and characterized further for biocompatibility, rheological and anti-staphylococcal activities. The antibacterial activity of MLEC hydrogel against S. aureus strains was verified using in vitro and ex vivo porcine skin model. Our results demonstrated MLEC hydrogel formulation may act as superior alternative to currently available topical antiseptic/antibiotic formulations for the treatment of drug resistant staphylococcal infections.