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• Toward synthesis of thioglycosyl-phosphonate analogues of lipid ll

  Viktor Kelemen

  Milán Csiszár

  Anikó Borbás

  Views:

  181

  Although a multitude of epidemics have already been eradicated with the use of modern antibiotics, in the 20th century, a new and increasingly serious phenomenon has arisen - the resistance against antibiotic therapies, necessiting the need for the development of novel antibiotic compounds. Transglycosylases are key enzymes in the biosynthesis of the bacterial cell wall, and currently there is no approved drug in human use against them, so they are an excellent target for further antibiotic development. During our research, the main goal was to synthesize compounds that are structurally similar to lipid ll, the substrate of bacterial transglycosylases, however, with significant modifications, such as the incorporation of an α-thioglycosidic unit instead of the α-O-glycosidic bond and an alkylphosphonate unit instead of the pyrophosphate part, making the molecules suitable to act as enzyme inhibitors. The key step of our work is the stereoselective construction of the 1,2-cis-α-thioglycosidic bond by photoinitiated thiol ene coupling reaction. ln this paper, the novel synthesis route is described which can be applied to furnish different lipid ll analogues, on example synthesis of a D-glucose derivative.

• Oral Testosterone Undecanoate Formulations for Testosterone Replacement Therapy

  Béla E. Tóth

  László Horváth

  Miklós Vecsernyés

  Views:

  48

  Male hypogonadism, or Testosterone Deficiency (TD), involves decreased testicular function, leading to low androgen levels and impaired sperm production. This condition can negatively impact quality of life and increase cardiovascular risks. The adult hypogonadism frequently occurs over 40 in men, and it is characterized by persistent symptoms alongside low testosterone levels, typically below 300 ng/dL. Supplementation with  testosterone as a replacement therapy (TRT) is  hormonal enhancement found to be effective, however the delivery methods vary, each with specific advantages and drawbacks. The TRT has potentially life-changing effects, patients feel improved quality of life in several aspects: more energy and muscular strength, increased libido, improved mood, etc. as the most ferquent patients reported outcome.

  Oral TRT, particularly testosterone undecanoate (TU), offers notable convenience. TU is absorbed via the lymphatic system, bypassing first-pass hepatic metabolism, making it a promising agent for TRT. Its absorption, however, is influenced by dietary factors, such as lipid intake, thus the high-fat consumption promoting lymphatic absorption. Pharmaceutical technology to address this dependency, newly developed TU formulations incorporate special self-emulsifying systems that enhance lymphatic absorption regardless of food fat content. This lymphatic absorption allows for stable testosterone levels, positioning TU as a viable also for an oral treatment option.