Mini Reviews in Medicinal Chemistry - Volume 17, Issue 7, 2017

Background: The design, medicinal chemistry, pharmacokinetics and development of the highly selective α2-adrenoceptor antagonist fluparoxan are reviewed. Method: The drug's activity and selectivity in vitro, its efficacy in animals and its excellent oral pharmacokinetics and central α2-adrenoceptor antagonist activity in man, are evaluated as well as its ability to increase extracellular levels of noradrenaline, dopamine and acetylcholine in vivo. Conclusion: Furthermore, its potential for the treatment of central neurodegenerative diseases is highlighted, in particular its improvement of cognitive dysfunction in schizophrenia and in models of Alzheimer's disease

Background: Breast cancer is the second leading cause of cancer-related deaths among women in the Western World. Method: Upon diagnosis and treatment in the preinvasive state, the five years survival rate levitate up to 93%, making early detection crucial for dedicative diagnosis and treatment. Currently, mammography is the most efficacious diagnostic modality. However, this technique does not match the ultimate sensitivity. Other routinely used biomarkers include tumor size, histological type, nuclear and cellular characteristics, mitotic index, vascular invasion, hormonal and axillary lymph node status were not good enough to predict the course of cancer. To date, researchers revealed a change in the level of some proteinases in breast cancer tissue and reported the role of these proteinases in tumor aggressiveness and patient response to therapy. Conclusion: This review summarizes the potential role of serine proteinases (including urokinasedependent plasminogen activator and kallikreins) and zinc metalloproteinases (including matrix metalloproteinase and A disintegrin and metalloproteinase) as either a prognostic and/or diagnostic breast cancer biomarkers. These proteinases plus genetic biomarkers could be implemented in the development of multiplex bio sensing platform toward early breast cancer detection, diagnosis, monitor progression and therapeutic success.

Background: Proliferation of the smooth muscle and epithelial cells within the prostatic transition zone in older men leads to benign prostatic hyperplasia (BPH), which is hallmarked by the troublesome lower urinary tract symptoms. The affair responsible for the initiation and promotion of disease is still unresolved, though alpha-blockers and 5α-reductase inhibitors are used as management options for relief from the dynamic and static components respectively. Method: Combination therapy including both the alpha blocker and 5α-reductase inhibitor is emerging as inclusive parcel for treatment. However, selective androgen receptor modulators (SARM) and selective estrogen receptor modulators (SERM) are the other management resources, which are in the limelight. Result: This review gives a glimpse of BPH and the various chemical entities which have been reported in literature till date for the condition since 2005.

Background: Acremonium fungi have been isolated from various sources, such as soil, plants, and marine organisms. Method: The species in Acremonium have been proved to be rich sources of novel and bioactive secondary metabolites. Up to now, 356 metabolites belonging to steroids (6 compounds), terpenoids (86), meroterpenoids (66), polyketides (89), alkaloids (28), peptides (75), and miscellaneous types (6) have been isolated from Acremonium fungi. These metabolites displayed a wide range of biological activities including antimicrobial, cytotoxic, antitumor, immunosuppressive, antioxidant, antiinflammatory, antimalarial, phytotoxic, tremorgenic, antiviral, neuritogenic, insecticidal and enzymesinhibiting activities. Conclusion: This review highlights the structures and bioactivities of the secondary metabolites from Acremonium fungi reported until July 2016.

Background: The water insolubility of fullerene C60 nanostructure greatly hampers its biological applications as an effective HIV-1 protease inhibitor, which suggests to synthesis new C60 derivatives with different functional polar groups. Method: The new carbon nanostructures of fulleropyrrolidines with one and two polar acetoxyhydroxyl (AcH) groups (C60-A and C60-B, respectively) were constructed to evaluate their interactions and binding affinity into HIV-1 protease active site via theoretical molecular docking and molecular dynamic simulations. Data obviously indicated the higher affinity of fulleropyrrolidines derivatives C60-A and C60-B compared to fullerene C60 in interacting with HIV-1 protease active site cavity. The functional groups in C60 caused better residing of C60 derivatives in the center of active site by changing the spherical shape of C60, constructing different stable H-bonds with supporting the main π interactions between C60 and aromatic Phe53/Arg8 in protease active site. Our finding showed that the functionalization of C60 is essential for both increasing solubility and improving different π interactions of C60 with protease. Also, H-bond forming with AcH functional groups and enzyme active site residues is more important to support the van der Waals interactions between C60 fragment of fulleropyrrolidines and enzyme cavity. Since enzyme possesses aspartic acid residues in active site, C60-B with two AcH groups interacted with the active site more efficiently via additional H-bond relative to C60-A. Results: Finally, the results indicate a possible use of the investigated fulleropyrrolidines derivatives as new HIV-1 protease inhibitors.