Search for: All records

Molecular targeting strategies have been used for years in order to control cancer progression and are often based on targeting various enzymes involved in metabolic pathways. Keeping this in mind, it is essential to determine the role of each enzyme in a particular metabolic pathway. In this review, we provide in-depth information on various enzymes such as ceramidase, sphingosine kinase, sphingomyelin synthase, dihydroceramide desaturase, and ceramide synthase which are associated with various types of cancers. We also discuss the physicochemical properties of well-studied inhibitors with natural product origins and their related structures in terms of these enzymes. Targeting ceramide metabolism exhibited promising mono- and combination therapies at preclinical stages in preventing cancer progression and cemented the significance of sphingolipid metabolism in cancer treatments. Targeting ceramide-metabolizing enzymes will help medicinal chemists design potent and selective small molecules for treating cancer progression at various levels. 

The development of inverse vulcanization has provided a simple method to create sulfur-based materials. The low cost, ease of synthesis, and variety of applications has led to a rapid expansion of the field. These polysulfides can be synthesized with a wide range of sulfur contents (20-90% S) depending on the desired properties. Garlic essential oil (GEO) has a high sulfur content, which offers the opportunity to replace sulfur, a petroleum byproduct, with a renewable monomer to make materials with moderate sulfur contents. Using a one-pot, solvent-free synthesis, comparable to inverse vulcanization, GEO can be polymerized to create renewable adhesives at temperatures as low as 120 °C with reaction times decreasing at higher temperatures. Here we have explored the composition of garlic oil from a variety of commercial suppliers by NMR. Through simple 1H NMR analysis, the major sulfur-containing compounds of GEO can be identified and differentiated by sulfur rank. These data were used to select garlic oils with varied compositions to examine the impact on the poly(GEO) properties using solubility, gel permeation chromatography, differential scanning calorimetry, and thermogravimetric analysis as well as adhesive performance. GEO was then subjected to different reaction times and temperatures and the degree of polymerization was monitored by 1H NMR. The polysulfides were then evaluated as adhesives at different extents of polymerization to better understand how the reaction conditions impact adhesive performance. The failure mode and mechanical properties of the polymers were analyzed using measurements of maximum adhesion strength and work of adhesion. This study has provided a better understanding of polymers formed from GEO, providing a viable route to developing renewable, S-based materials. 

Despite adhesives having their origins in natural materials, most glues are formed from petroleum-based products. However, many natural adhesives lack the strength to compete with synthetic glues. Therefore, strong, sustainable alternatives are needed. Data presented here build on prior work that combines elemental sulfur, a petroleum byproduct, and garlic essential oil (GEO) which is composed of allyl sulfides, to make adhesives. Here, we have demonstrated that both sulfur and GEO can initiate polymerization at 160 °C with another petroleum byproduct, dicyclopentadiene, and a variety of natural monomers through the formation of sulfur radicals. In addition to using natural monomers and petroleum byproducts, these processes are solvent free and have high atom economy, limiting waste formation, and meeting many principles of green chemistry. Much of this work has focused on determining the effect of each sulfur source on polymerization and adhesion. A family of polymers were created with varied S : GEO : monomer ratios and characterized to determine differences in their chemical and materials properties. Despite similarities in the reaction mechanism, sulfur tends to polymerize more rapidly and create materials that are more ductile and more easily reprocessed. GEO is slower to react causing more polymerization to take place on the adherend surface yielding a more brittle polymer with higher maximum adhesion strength but lower work of adhesion. Both polymers exhibited effective adhesive recyclability. Overall, a combination of natural oils and petroleum byproducts were combined to make inexpensive, sustainable, recyclable adhesives. 

Sphingomyelin is a cell membrane sphingolipid that is upregulated in synovial sarcoma (SS). Jaspine B has been shown to inhibit sphingomyelin synthase, which synthesizes sphingomyelin from ceramide, a critical signal transducer; however, jaspine B’s low bioavailability limits its application as a promising treatment option. To address this shortcoming, we used microfluidics to develop a liposomal delivery system with increased anticancer efficacy. The nano-liposome size was determined by transmission electron microscopy. The jaspine B liposome was tested for its tumor inhibitory efficacy compared to plain jaspine B in in vitro and in vivo studies. The human SS cell line was tested for cell viability using varying jaspine B concentrations. In a mouse model of SS, tumor growth suppression was evaluated during four weeks of treatment (3 times/week). The results show that jaspine B was successfully formulated in the liposomes with a size ranging from 127.5 ± 61.2 nm. The MTT assay and animal study results indicate that jaspine B liposomes dose-dependently lowers cell viability in the SS cell line and effectively suppresses tumor cell growth in the SS animal model. The novel liposome drug delivery system addresses jaspine B’s low bioavailability issues and improves its therapeutic efficacy.