Mini-Reviews in Organic Chemistry - Volume 14, Issue 4, 2017

Polyether antibiotics (ionophores) represent a large group of lipophilic compounds which are able to form complexes with the metal cations and transport them across the lipid membranes. This process disturbs the intercellular Na+/K+ concentration gradient and intracellular pH and leads to the mitochondrial injuries, cell swelling, vacuolization and finally to apoptosis process. For this reason, ionophores are commonly used in veterinary medicine as the non-hormonal growth-promoting and coccidiostatic agents. In this group, particularly interesting are monensin and salinomycin because of their proved anti-tumour activity, including efficiency against multidrug-resistant cancer cells and cancer stem cells. Prompted by the idea that cancer cells may be individually effectively killed by these compounds, a very interesting direction of research is bioconjugation process of ionophores. This review is focused on the possible role of hybrids of ionophore antibiotics with other biologically active substances in anti-cancer and anti-bacterial treatment and gives an overview of their properties.

A majority of the world’s population continues to use traditional natural medicines based on the established knowledge of local plants for the treatment of various disease states. Often the same plant is recognized having several traditional uses. For the past few decades, the idea of "one drug, one activity, one disease" has dominated drug discovery in Western medicine, the so-called “magic bullet” approach. However, this view has been transformed through the discovery of the multi-targeting of bioactive compounds, which has opened up new areas for pharmaceutical development wherein the same drug may be simultaneously approved for the treatment of different diseases. Pursuing that discovery pathway, a wide variety of natural products have been evaluated for their multiple biological characteristics, such as analgesic, anti-proliferative, anti-inflammatory, anti-bacterial and anti-oxidant effects, among others. This mini-review highlights some of the recent findings concerning multi-target bioactive, plant-derived metabolites with a special emphasis on alkaloids and terpenoids. The alkaloids selected were colchicine, capsaicin, and vincristine, while the terpenoids chosen were artemisinin, taxol (paclitaxel), and masticadienonic acid. Issues relating to the sustainability of supply, and the efficiency of future drug discovery based on network pharmacology approaches are also mentioned.

Neurodegenerative diseases are linked with high morbidity and mortality rates. Medical science has made considerable progress in understanding the mechanisms associated with the development of the neurodegenerative diseases. Each neurodegenerative disease is associated with precise pathways of cell death with its own mechanisms that lead to the development of novel therapeutic strategies for each case. In spite of various western medicines available, there still remains too many complications to manage the progressive and severe symptoms of these diseases. Ayurveda is not the mainstream treatment system, but it can provide better results than mainstream medications, with less severe side effects. A detailed study, scientific validation and standardization of the active biomolecules of herbal-mineral formulations are required for the evolution of ayurvedic medicines. This review is a concerted effort to identify the major ayurvedic formulations and treatment strategies based on Ayurvedic literature for the treatment of neurodegenerative disorders.

The ocean covers about 75% of earth’s surface and harbours an infinite source of potential pharmacologically active organic metabolites which are yet to be explored. With the increase of noncommunicable and infectious diseases threatening public health and a dearth of existing drugs, researchers are constantly in the quest for novel bioactive template compounds from natural products. This mini-review aims at bringing to the limelight of the scientific community the polypharmacological potential of marine natural organic products against common chronic diseases. Key databases were probed for relevant publications geared towards pharmacological properties of marine products. Pathologies targeted correlating with the medicinal properties of marine sponges and seaweeds were grouped into four categories namely; cardiovascular diseases, diabetes, cancer, and HIV. The possible mechanisms of metabolites isolated from these marine products were also discussed. Callyspongynic acid derived from sponge was found to be both effective as anti-diabetic and antiviral. It was noted that congeneric marine sponges’ unique chemical characteristics depend on their geographical location and environment. Moreover, a seaweed derived-metabolite (fucoidan) was found to be beneficial in the management of obesity on long-term treatment, to have hypoglycemic effect on type 2 diabetes and to act as an anti-cancer agent. The myriad of marine metabolites combined to the global awareness of the undiscovered pharmacological potential of marine organisms could increase the pace of these products entering clinical trials. This mini-review advocates for the exploitation of marine products towards the production of novel therapeutic drugs. In conclusion, it was found that the use of marine derived bioactive products could provide a plethora of alternative strategies for clinical applications.

Up to now, the polypharmacology of diterpene alkaloids isolated from Aconitum and Delphinium sp. has been extensively studied. From 1998 to 2014, more than 400 new diterpene alkaloids were isolated from Nature. Pharmacological researches have indicated that many diterpenoid alkaloids are the main bioactive components which have arrhythmogenic, local anesthetic, antiarrhythmic, curariform, analgesic, hypotensive, anti-inflammatory, anti-microbial, anti-tumor, spasmolytic, neurotropic and psychotropic activities. In the present review, the antiarrhythmic, analgesic and anti-inflammatory activities of diterpene alkaloids as well as the pharmacological mechanisms were summarized. Moreover, their Structure-Activity Relationship was also analyzed.

Curcumin, a polyphenolic pigment of turmeric, is one of the very promising natural products that have been extensively investigated from both the biological and structural point of view. It has been shown to possess activity towards variety of targets at cellular and molecular levels that provide a basis for its use against multiple human diseases. In recent decades, it has been subjected to various pharmacological, biochemical and clinical investigations which proposed its multifaceted therapeutic potential being attributed mainly to its unique chemical structure and physicochemical properties. Thus, this review discusses the structure-activity relationship of curcumin in relation to its biological activities to gain more understanding on the mechanistic basis of its therapeutic action. Curcumin is a diferuloylmethane molecule with two ferulic acid residues joined by a seven carbon methylene bridge. The three important structural features of curcumin include two aromatic o-methoxy phenolic groups, β-dicarbonyl moiety and a seven carbon linker containing two enone moeities. Extensive research in the last two decades has provided evidence for the role of these different functional groups in its crucial biological activities. In addition to this, the polypharmacology of curcumin may also be attributed to the unexpected chemical diversity exhibited by its metabolites. Structural modifications in these specific functional moeities of curcumin have led to the development of new analogues with improved physicochemical properties and biological activity either by affecting its solubility, specificity or potency. Thus, the understanding of such structure-activity relationship may impose the exploration of the range of its biological activity.

With the aim of offering patients a more effective drug therapy and with few side effects, it was believed in the perfect and unique interaction of the bioactive compound and the receptor or target macromolecule. This concept has changed, and multifunctional compounds show greater efficiency, particularly in the therapy of complex diseases, with a sum of origin. Among these ills, we quote: neurodegenerative diseases, cancer, parasitic and inflammatory. To fight these diseases, studies with multitarget flavonoids have been reported. Flavonoid compounds are natural products traditionally used as chemotherapy because of their numerous therapeutic activities. Here, we gather studies with multitarget in drug discovery flavonoids.

Plant secondary metabolites are considered as a valuable source to identify promising lead compounds for developing novel drugs. Platycodin D is regarded as one of the major bioactive compounds in medicinal plant Platycodon grandiflorum, which attracts researchers to study its therapeutic effect recently. This paper reviews the latest research of biological and pharmacological activities of platycodin D. In vitro and in vivo experimental evidences have revealed that platycodin D demonstrates multiple pharmacological properties including anti-oxidative, anti-inflammatory, anticancer, antiobesity and hepatoprotective effects. The underlying mechanisms of multiple therapeutic functions of platycodin D are very likely associated with its anti-inflammatory and antioxidant nature, whereas low bioavailability should be considered in drug development.