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.

Cancer metastases: Tailoring the targets.

Metastasis is an intricate and formidable pathophysiological process encompassing the dissemination of cancer cells from the primary tumour body to distant organs. It stands as a profound and devastating phenomenon that constitutes the primary driver of cancer-related mortality. Despite great strides of advancements in cancer research and treatment, tailored anti-metastasis therapies are either lacking or have shown limited success, necessitating a deeper understanding of the intrinsic elements driving cancer invasiveness. This comprehensive review presents a contemporary elucidation of pivotal facets within the realm of cancer metastasis, commencing with the intricate processes of homing and invasion. The process of angiogenesis, which supports tumour growth and metastasis, is addressed, along with the pre-metastatic niche, wherein the primary tumour prepares for a favorable microenvironment at distant sites for subsequent metastatic colonization. The landscape of metastasis-related genetic and epigenetic mechanisms, involvement of metastasis genes and metastasis suppressor genes, and microRNAs (miRNA) are also discussed. Furthermore, immune modulators' impact on metastasis and their potential as therapeutic targets are addressed. The interplay between cancer cells and the immune system, including immune evasion mechanisms employed by metastatic cells, is discussed, highlighting the importance of targeting immune modulation in arresting metastatic progression. Finally, this review presents promising treatment opportunities derived from the insights gained into the mechanisms of metastasis. Identifying novel therapeutic targets and developing innovative strategies to disrupt the metastatic cascade holds excellent potential for improving patient outcomes and ultimately reducing cancer-related mortality.

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.