RESUMEN
Fluorine-containing heterocycles continue to receive considerable attention due to their unique properties. In medicinal chemistry, the incorporation of fluorine in small molecules imparts a significant enhancement their biological activities compared to non-fluorinated molecules. In this short review, we will highlight the importance of incorporating fluorine as a basic appendage in benzothiazole and benzimidazole skeletons. The chemistry and pharmacological activities of heterocycles containing fluorine during the past years are compiled and discussed.
Asunto(s)
Bencimidazoles/química , Benzotiazoles/química , Flúor/química , Compuestos Heterocíclicos con 2 Anillos/química , Relación Estructura-Actividad , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Bencimidazoles/farmacología , Benzotiazoles/farmacología , Química Farmacéutica/métodos , Diseño de Fármacos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Compuestos Heterocíclicos con 2 Anillos/farmacología , HumanosRESUMEN
Ras GTPases are key players in cellular signalling because they act as binary switches. These states manifest through toggling between an active (GTP-loaded) and an inactive (GDP-loaded) form. The hydrolysis and replenishing of GTP is controlled by two additional protein classes: GAP (GTPase-activating)- and GEF (Guanine nucleotide exchange factors)-proteins. The complex interplay of the proteins is known as the GTPase-cycle. Several point mutations of the Ras protein deregulate this cycle. Mutations in Ras are associated with up to one-third of human cancers. The three isoforms of Ras (H, N, K) exhibit high sequence similarity and mainly differ in a region called HVR (hypervariable region). The HVR governs the differential action and cellular distribution of the three isoforms. Rheb is a Ras-like GTPase that is conserved from yeast to mammals. Rheb is mainly involved in activation of cell growth through stimulation of mTORC1 activity. In this review, we summarise multidimensional NMR studies on Rheb and Ras carried out to characterise their structure-function relationship and explain how the activity of these small GTPases can be modulated by low molecular weight compounds. These might help to design GTPase-selective antagonists for treatment of cancer and brain disease.
Asunto(s)
Espectroscopía de Resonancia Magnética/métodos , Proteínas ras/química , Proteínas ras/metabolismo , Animales , Proteínas Activadoras de GTPasa/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Humanos , Bibliotecas de Moléculas Pequeñas/farmacologíaRESUMEN
To design new compounds suitable as starting points for anticancer drug development, we have synthesized a novel series of benzoxazoles with pharmaceutically advantageous piperazine and fluorine moieties attached to them. The newly synthesized benzoxazoles and their corresponding precursors were evaluated for cytotoxicity on human A-549 lung carcinoma cells and non-cancer HepaRG hepatocyes. Some of these new benzoxazoles show potential anticancer activity, while two of the intermediates show lung cancer selective properties at low concentrations where healthy cells are unaffected, indicating a selectivity window for anticancer compounds.
RESUMEN
Chitin is the second most abundant natural biopolymer, which is composed of N-acetyl glucosamine units linked by ß-(1 â 4) Chitosan is an N-deacetylated product of chitin. Properties of chitosan and chitin, such as biocompatibility, non-toxic nature, and biodegradability, make them successful alternatives for energy and environmental applications. However, their low mechanical properties, small surface area, reduced thermal properties, and greater pore volume restrict the potential for adsorption applications. Multiple investigations have demonstrated that these flaws can be prevented by fabricating chitosan and chitin with carbon-based composites. This review presents a comprehensive analysis of the fabrication of chitosan/chitin carbon-based materials. Furthermore, this review examines the prevalent technologies of functionalizing chitosan/chitin biopolymers and applications of chitin and chitosan as well as chitosan/chitin carbon-based composites, in various environmental fields (mitigating diverse water contaminants and developing biosensors). Also, the subsequent regeneration and reuse of adsorbents were also discussed. Finally, we summarize a concise overview of the difficulties and potential opportunities associated with the utilization of chitosan/chitin carbon-based composites as adsorbents to remove water contaminants.
Asunto(s)
Carbono , Quitina , Quitosano , Adsorción , Quitosano/química , Carbono/química , Quitina/química , Biopolímeros/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodosRESUMEN
Cancer is a group of heterogeneous diseases that occur when cells in the body proliferate and divide uncontrollably. As the current treatment modalities have pros and cons, the discovery of new chemotherapeutic agents with the least side effects is one of the most investigated research areas. In this context, plant-based natural products are a rich source of drugs and have served humanity for ages. Frankincense essential oils (FEOs) are among the most promising plant-based oils in Gulf countries. In addition to their high cultural value, FEOs are also famous for their engaging biological activities, including anti-cancerous. However, the practical application of FEOs is often hindered/by their low water solubility, limited bioavailability, high volatility, and sensitivity toward heat, humidity, light, or oxygen. Thus, a significant demand for technological advancement would improve their ability to target particular cells and tissues. Nanotechnology emerged as an exciting approach in this context. Through suitable nano-formulation (functionalization or encapsulation into a nanostructure), issues arising due to solubility, targeting capability, and delivery can be controlled.
RESUMEN
The reaction of 3-methyseleno-2-methylselenomethyl-propene with benzyl 2,3-anhydro-4-O-triflyl-ß-L-ribopyranoside provides a major convenient enantiomeric product of 1-methylene-(benzyl3,4-dideoxy-α-D-arabinopyranoso)-[3,4-c]-cyclopentane, with benzyl-2,3-anhydro-4-deoxy-4-C-(2-methyl- propen-3-yl)-α-D-lyxopyranoside as a minor product. While the reaction of 3-methyseleno-2-[methylselenomethyl]-propene with benzyl 2,3-anhydro-4-O-triflyl-α-D-ribopyranoside produces a good yield of benzyl-2,3-anhydro-4-deoxy-4-C-(2-methylpropen-3-yl)-α-D-lyxo-pyranoside. Molecular modeling and molecular dynamics simulations indicate that the intermediate in the reaction of the ß-L sugar frequently occupies an optimal conformation that leads to the formation of cyclopentane, while the intermediate in the reaction of the α-D sugar has a very small probability. The results point to the dominant role of the ß-L sugar intermediate in controlling the cyclopentane formation.