Current Medicinal Chemistry - Volume 24, Issue 25, 2017

Background: Gold nanoparticles (AuNPs) have enormous potential for application in imaging, diagnosis, and therapies in the medical field. AuNPs are renowned for their localized surface plasmon resonance (LSPR) properties, large surface area, and biocompatibility with body fluids. Further, AuNPs have featured prominently in new methodologies for cancer treatments, like photothermal and imaging therapies. Although AuNPs present enormous potential for application in the medical field, their instability under physiological conditions prevents further uses. However, this limitation may be overcome by associating AuNPs with biopolymers. To the best of our knowledge, a revision paper rationalizing the structure/property relationship and applications of AuNPspolysaccharide composites in the medical field has not been published yet. Methods: This manuscript discusses the most relevant aspects and state-of-art concepts surrounding the synthesis of AuNPs based on green chemistry and their association with polysaccharides that can efficiently function both as stabilizing and reducing agents of Au nanoparticles. Even more, polysaccharide devices may inhibit non-specific interactions between AuNPs and biological macromolecules, suppressing unsuitable “protein corona” formations on AuNP surfaces, thereby increasing the potential of AuNP composites of being employing as drug delivery matrices and wound-healing devices as well as in photothermal/ imaging purposes for cancer treatments and biosensors.

Thalidomide is a drug with interesting therapeutic properties but also with severe side effects which require a careful and monitored use. Potential immunomodulatory, antiinflammatory, anti-angiogenic and sedative properties make thalidomide a good candidate for the treatment of several diseases such as multiple myeloma. Through an increase in the degradation of TNFα-mRNA, thalidomide reduces the production of TNFα by monocytes and macrophages stimulated by lipopolysaccharide or by T lymphocytes induced by mitogenic stimuli. The decreased level of TNFα alters the mechanisms of intracellular transduction by preventing the activation of NF-kB and by decreasing the synthesis of proteins, in particular IL-6, involved in cell proliferation, inflammation, angiogenesis and protection from apoptosis. Furthermore, thalidomide affects VEGF levels by down-regulating its expression. Nowadays, new safer and less toxic drugs, analogs of thalidomide, are emerging as beneficial for a more targeted treatment of multiple myeloma and several other diseases such as Crohn's disease, rheumatoid arthritis, sarcoidosis, erythema nodosum leprosum, graft-versus-host disease.

Background: The group of fluorophores on boron dipyrrin platform (4,4-difluoro-4-bora3a,4a-diaza-s-indacene, also known as BODIPY) has attracted much attention in the field of molecular sensorics, including sensing of biomolecules and bioprocesses. Structural diversity of existing BODIPY with ample opportunities of directed modification of compounds makes this class of fluorophores attractive for medical and biological purposes. The recent progress in the design and functionalization of BODIPY allows using them for modification of drug micro- and nanocarriers in order to improve their therapeutic effect in cancer treatment. At the same time, integration of BODIPY into drug carriers provides the possibility of in vitro and in vivo real time imaging of used drug carriers. The high fluorescent intensity and low toxicity of BODIPY granted for conjugation with different biomolecules. Results: The present review focuses on the recent advances for application of individual BODIPY in medical diagnostics, antimicrobial activity, as well as establishing the role of BODIPY in labeling of biomolecules (e.g. proteins, hormones and DNA). Also the review highlights the potential of BODIPY in functionalization of drug micro- and nanocarriers in order to achieve better therapeutic efficiency compared with non-modified materials. The advantages derived from the use of BODIPY for preparation and modification of drug carriers are critically evaluated and potential for future challenges, especially concerning the design of innovative multi-functional BODIPY-based nanocarriers, is discussed in detail using representative examples from literature. Conclusion: Our objective was to show that BODIPY are powerful tools for bioimaging, labeling of biomolecules and construction of new multifunctional drug carriers.

Cyclic dipeptides are the simplest peptide derivatives commonly found in nature. These chiral molecules are easily synthesized from readily available α-amino acids using a simple methodology. They are privileged structures with the ability to bind to a wide range of receptors and have a broad variety of biological and pharmacological activities. We will give a brief overview of their status giving and interesting reference list about the last works.

Background: In the last two decades, there have been significant technological advances in the early detection of brain tumors. However, no notable improvements have been observed in the treatment of Glioblastoma Multiforme (GBM), the most common brain neoplasm coupled with the worst prognosis. GBM is characterized by an extensive resistance to a broad spectrum of anti-tumor drugs. This property is the result of a phenomenon known as Multiple Drug Resistance (MDR), which significantly limits noninvasive alternative therapies. This limitation is primarily due to the activity of ABC transporters and proteins related with DNA repair such as the MGMT enzyme. Due to the high mortality rate in GBM patients and current treatment deficits, new therapeutic strategies for this type of neoplasm are of vital importance. Methods: In this review, proposed treatments for GBM, including the use of alkylating agents with MGMT inhibitors, MDR modulators, and immunotherapies are discussed. We focused our bibliographic research on papers containing in vitro, in vivo, and clinical phase analysis published over the last 20 years. Results: Several studies have demonstrated good results using alkylating agents plus MGMT inhibitors, although without great improvements in survival. The use of modulators of ABC transporters enhances the effects of chemotherapy, proving it an effective complementary therapy. Immunotherapies have undergone significant developments as a directed and personalized approach for GBM treatment. Conclusion: The use of alternative complementary therapies discussed in this review could increase the survival of GBM patients; however, additional clinical phase analysis and the generation of new treatment protocols are required.

Since their first synthesis back in the early 20th century, 1,2,4-triazolo[1,5-a]pyrimidines have aroused increasing interest in very diverse areas ranging from chemotherapy to agriculture or even photography. Their similarity to purines confers a potential bioactivity and this feature has been wisely exploited for therapeutic use, including antifungal, antipyretic, analgesic, antiinflammatory, antitumoral and antiparasitic properties. In this review, we focus on the compounds that these nitrogen heterocycles form with metal ions and their antiparasitic activity and therapeutic potential against two neglected diseases of tropical prevalence, leishmaniasis and Chagas disease.