Current Topics in Medicinal Chemistry - Volume 19, Issue 32, 2019

This special issue of Current Topic in Medicinal Chemistry (CTMC) covers outcomes and ideas for future molecular modifications leading to the novel derivatives with better constructive pharmacological potential for treatment of the different human disorders but also may considering anatomical features of the underlying tissues, and non-chemical based treatment strategies.

Natural product therapy has been gaining therapeutic importance against various diseases, including cancer. The failure of chemotherapy due to its associated adverse effects promoted adjunct therapy with natural products. Phytochemicals exert anti-carcinogenic activities through the regulation of various cell signaling pathways such as cell survival, inflammation, apoptosis, autophagy and metastasis. The ‘small molecule-chemosensitizing agents’ from plants induce apoptosis in drug-resistant and host-immune resistant cancer cells in in vitro as well as in vivo models. For example, alkaloids from Nelumbo nucifera, liensinine, isoliensinine and neferine exert the anticancer activity through enhanced ROS generation, activation of MAP kinases, followed by induction of autophagy and apoptotic cell death. Likewise, these alkaloids also exert their cytoprotective action against cerebrovascular stroke/ischemic stroke, diabetes, and chemotherapy-induced cytotoxicity. Therefore, the present review elucidates the pharmacological activities of these bisbenzylisoquinoline alkaloids which include the cytoprotective, anticancer and chemosensitizing abilities against various diseases such as cardiovascular diseases, neurological diseases and cancer.

Proteins are versatile macromolecules that perform a variety of functions and participate in virtually all cellular processes. The functionality of a protein greatly depends on its structure and alterations may result in the development of diseases. Most well-known of these are protein misfolding disorders, which include Alzheimer’s and Parkinson’s diseases as well as type 2 diabetes mellitus, where soluble proteins transition into insoluble amyloid fibrils. Atomic Force Microscopy (AFM) is capable of providing a topographical map of the protein and/or its aggregates, as well as probing the nanomechanical properties of a sample. Moreover, AFM requires relatively simple sample preparation, which presents the possibility of combining this technique with other research modalities, such as confocal laser scanning microscopy, Raman spectroscopy and stimulated emission depletion microscopy. In this review, the basic principles of AFM are discussed, followed by a brief overview of how it has been applied in biological research. Finally, we focus specifically on its use as a characterisation method to study protein structure at the nanoscale in pathophysiological conditions, considering both molecules implicated in disease pathogenesis and the plasma protein fibrinogen. In conclusion, AFM is a userfriendly tool that supplies multi-parametric data, rendering it a most valuable technique.

Objective: Glioblastoma is a highly aggressive and invasive brain and Central Nervous System (CNS) tumor. Current treatment options do not prolong overall survival significantly because the disease is highly prone to relapse. Therefore, research to find new therapies is of paramount importance. It has been discovered that glioblastomas contain a population of cells with stem-like properties and that these cells are may be responsible for tumor recurrence. Methods: A review of relevant papers and clinical trials in the field was conducted. A PubMed search with related keywords was used to gather the data. For example, “glioblastoma stem cells AND WNT signaling” is an example used to find information on clinical trials using the database ClinicalTrials.gov. Results: Cancer stem cell research has several fundamental issues and uncertainties that should be taken into consideration. Theoretically, a number of treatment options that target glioblastoma stem cells are available for patients. However, only a few of them have obtained promising results in clinical trials. Several strategies are still under investigation. Conclusion: The majority of treatments to target cancer stem cells have failed during clinical trials. Taking into account a number of biases in the field and the number of unsuccessful investigations, the application of the cancer stem cells concept is questionable in clinical settings, at least with respect to glioblastoma.

Background: Breast plastic surgery is a rapidly evolving field of medicine. The modern view of surgical trends reflects the desire to minimize complications and introduce advanced technologies. These always will be priorities for surgeons. Reconstructive surgery, a branch of plastic surgery focusing on restoration of lost functional and aesthetic component, seeks to enhance psychological rehabilitation and improves the quality of life, as well as aesthetic recovery. Objective: This review addresses the action of fibrin agents and their effect on the quality of surgical hemostasis. Discussion and Conclusion: The fundamental goals for the surgeon are to perform a minimally traumatic intervention and to prevent any form of complication. Achieving complete hemostasis is an intraoperative necessity. Timely prevention of bleeding and hemorrhagic phenomena can affect not only the outcome of the operation, but also the incidence of postoperative complications. Topics include the integrity of microvascular anastomoses, tissue adhesion, and the incidence of seromas and hematomas associated with fibrin glue usage. The literature on fibrin adhesives with respect to prevention of postoperative complications, and the effectiveness with active drainage also are analyzed.

Background: There is a dearth of published information on the posterior perforated substance as compared to the anterior perforated substance. We managed to glean facts about the posterior perforated substance that can serve as a landmark for surgical operations in the adjacent regions of the midbrain and the vessels passing through it. Moreover, the posterior perforated substance contains the interpeduncular nucleus responsible for the mental state of the individual. Objectives: 1) To describe the topography of the blood vessels supplying the posterior perforated substance area from the surgical point of view; 2) to investigate the functions of the interpeduncular nucleus. Methods: We assembled and analyzed results from source databases by Elsevier, NCBI MedLine, Scopus, Scholar. Google and Embase. Each article was studied in detail for practically useful information about the posterior perforated substance. Results: The P1-segment perforating branches of the posterior cerebral artery supply the posterior perforated substance. This area is especially vulnerable in the case of vascular pathologies. The posterior communicating artery can block the surgeon’s view and impede maneuverability of the tool in the area of the posterior perforated substance, which may be addressed using the separation technique, which can lead to positive results. In addition, the medial habenula-interpeduncular nucleus in the posterior perforated substance is associated with various addictions and psychiatric conditions. Conclusion: The posterior perforated substance area is of great interest for surgical interventions. Future studies of the interpeduncular nucleus anticipate the development of drugs to affect different types of dependencies and some mental diseases.

Bioactive antioxidant agents present in selected plants are known to provide the first line of biological defense against oxidative stress. In particular, soluble vitamin C, E, carotenoids and phenolic compounds have demonstrated crucial biological effects in cells against oxidative damage, preventing prevalent chronic diseases, such as diabetes, cancer and cardiovascular disease. The reported wide range of effects that included anti-aging, anti-atherosclerosis, anti-inflammatory and anticancer activity were studied against degenerative pathologies of the brain. Vitamins and different phytochemicals are important epigenetic modifiers that prevent neurodegeneration. In order to explore the potential antioxidant sources in functional foods and nutraceuticals against neurodegeneration, the present paper aims to show a comprehensive assessment of antioxidant activity at chemical and cellular levels. The effects of the different bioactive compounds available and their antioxidant activity through an epigenetic point of view are also discussed.