Topic Review
Alzheimer's disease
Alzheimer's disease (AD) is a multifactorial disease and the most common neurodegenerative disorder affecting the elderly population world-wide.The used medications treat the symptoms of AD, but without any delay on the progression of the disease. Curcumin presented favorable effects on AD. In the last decade curcumin analogues and derivatives have been synthesized in an attempt to optimize the beneficial properties of curcumin and improve its absorbance and  distribution per os as a therapeutic agent. Reviewing the bibliographical data of the last decade, information on the structures and / or chemical groups that are associated with specific action against AD, was gathered, derived from docking studies, (Q)SAR from vitro and in vivo tests. Phenolic hydroxyl groups might contribute to the anti-amyloidogenic activity. Phenyl methoxy groups seems to contribute to the suppression of Aβ42 and to the suppression of APP. Hydrophobic interactions revealed to be important. The presence of flexible moieties at the linker are crucial for the inhibition of Aβ aggregation. The inhibitory activity of derivatives is increased with the expansion of the aromatic rings. The keto-enol tautomer form offers as a new modification for the design of amyloid-binding agents. Taking the above under consideration  innovative design  and synthesis will lead to more potent and specific curcumin analogues and derivatives against AD.
  • 629
  • 30 Oct 2020
Topic Review
SARS-CoV-2 Main Protease
The main protease (Mpro) of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was subjected to hyphenated pharmacophoric-based and structural-based virtual screenings using a library of microbial natural products (>24,000 compounds). Subsequent filtering of the resulted hits according to Lipinski’s rules was applied to select only the drug-like molecules. Top-scoring hits were further filtered out depending on their ability to show constant good binding affinities towards the molecular dynamic simulation (MDS)-derived enzyme’s conformers. Final MDS experiments were performed on the ligand-protein complexes to verify their binding modes and calculate their binding free energy. Consequently, a final selection of six compounds of microbial origin was proposed to possess high potential as anti-SARS-CoV-2 drug candidates. Our study provides insight into the role of the Mpro structural flexibility during interactions with the possible inhibitors and sheds light on the structure-based design of anti-coronavirus disease 2019 (COVID-19) therapeutics targeting SARS-CoV-2
  • 623
  • 26 Oct 2020
Topic Review
Zinc Complexes as Anticancer Agents
The search for anticancer metal-based drugs alternative to platinum derivatives could not exclude zinc derivatives due to the importance of this metal for the correct functioning of the human body. Zinc, the second most abundant trace element in the human body, is one of the most important micro-elements essential for human physiology. Its ubiquity in thousands of proteins and enzymes is related to its chemical features, in particular, its lack of redox activity and its ability to support different coordination geometries and to promote fast ligands exchange. Analogously to other trace elements, the impairment of its homeostasis can lead to various diseases and in some cases can be also related to cancer development. However, zinc complexes generally exert lower toxicity in comparison to other metal-based drugs and many zinc derivatives have been proposed as antitumor agents. Among them zinc complexes  comprising  N-donor ligands have been surveyed and analyzed. 
  • 580
  • 22 Dec 2020
Topic Review
Cardiac Glycosides
Cardiac glycosides (CG’s) are naturally occurring biologically active small molecules, used to diagnose a diversity of heart diseases such as congestive heart failure and cardiac arrhythmia. The story of CG’s started over 100 years ago when Sir William Withering reported the use of foxglove plant for treating “dropsy” associated with congestive heart failure and the foxglove plant (Digitalis purpurea) was still in the use for the extraction of Digoxin, a cardiac glycoside used to treat congestive heart failures (Johnson., 2012). The core structure of CGs comprises a steroid nucleus attached to a five-membered lactone ring (cardenolide) or six-membered lactone rings (bufadienolides) along with sugar moieties. Major plant-derived CGs were obtained from plant families of Apocynaceae, Scrophulariaceae, and Asparagaceae (Thevitia neriifolia, Neerium oleander, Digitalis purpurea, Digitalis lanata, Urginea maritime, and Strophanthus kombe). Structurally, all these contain a core steroid nucleus connected with sugar moiety at C3 position and lactone moiety at C17 position (Figure 1.3). The pharmacological significance of all the CG’s lies in the core steroid confirmation that contains A/B and C/D cis- portions and the properties such as pharmacokinetics and pharmacodynamics lie between the confined sugars molecules (Pongrakhananon., 2013). Apart from the plant sources, CG’s were also isolated from several animal species such as bufadienolide was isolated from frogs, and also mammalian tissues contain a cardiac glycoside which is similar to endogenous digitalis (Melero et al., 2000). Quite a few studies have conveyed that the human body does contain a lot more CG’s in different parts. For example, the plasma membrane contains Ouabain and Proscillaridin A and human urine contains digoxin and marinobufagenin whereas human lenses consist of 19-norbufalin (Schoner and Scheiner-Bobis., 2007). In the year 1785, William Withering was the first person to use a digitalis compound from Digitalis purpurea to treat congestive heart failures. Currently, Digoxin is used for treating congestive heart failures. The mechanism of action of Digoxin is that it can inhibit the sodium-potassium pump (Na+/K+-ATPase). Living organisms maintain more percentage of K+ within the cell and less percentage of Na+. However, the scenario at the outside of the cell is quite opposite to the intracellular conditions where a high percentage of Na+ and less percentage of K+ will be maintained. Hence, there is a concentration incline that exists between the outside and inside cellular environments, which will be maintained by sodium-potassium pump. The Na+/K+-ATPase is recognized as a transmembrane protein whose functions are to maintain ionic balance in the heart tissue. Na+/K+-ATPase utilizes ATP as the whole energy source, to exchange two K+ ions inside the cell and pushes three Na+ ions outside to maintain intra cellular homeostasis. Also, Na+/K+-ATPase transports glucose and amino acids by keeping less concentration of Na+ within the cell and helps in the maintenance of electrochemical incline. The increment of the Na+ level inside the cell retort to CGs fortifies the ion exchange mechanism. This leads to the expansion of intracellular Ca2+ percentage which therefore promotes organelle instances such as myocardial contractibility, and generates optimistic inotropic effects in the heart cell with CGs (Kaplan., 2002).  
  • 571
  • 12 Aug 2020
Topic Review
Phlorotannins represent an important group of phenolic compounds, exclusively occurring in brown algae that can form simple structures of 126 Da to very large and complex polymers. Although the biosynthetic pathway of these compounds is still not consensual, it is known that they are formed via C–C and/or C–O–C oxidative coupling of several monomeric units of phloroglucinol, which in turn is known to be biosynthesized through the acetate–malonate pathway. According to the type of linkage formed between these units and the number of hydroxyl groups, phlorotannins can be classified in four sub-classes, namely phlorethols and fuhalols (ether linkages), fucols (aryl-aryl linkages), fucophlorethols (aryl-aryl and ether linkages), and eckols and carmalols (dibenzodoxine linkage).
  • 570
  • 21 Jul 2021
Topic Review
Ginger in its many forms, from juices of the fresh rhizome, to ginger powder and ginger essential oil, is growing in popularity for claimed universal health benefits. Nevertheless, and contrarily to the common notion of the public, ginger is not devoid of side effects, especially interactions with other drugs, and many of the claimed benefits remain to be substantiated. 
  • 566
  • 17 Jun 2021
Topic Review
Polymeric Nanoparticles in Cardiovascular Diseases
Nanoparticles, including biodegradable polymeric nanoparticles, are able to increase the efficiency and reduce the degradability of natural polyphenols, thus increasing their beneficial abilities in the target tissues. Resveratrol-, quercetin-, or curcumin-loaded polymeric nanoparticles have been shown to markedly reduce reactive oxygen species formation, the inflammatory process, apoptosis, lipid peroxidation, cardiac hypertrophy, and even to delay myocardium injury due to ischemia/reperfusion. Thus, polymeric nanoparticles represent a promising tool for the delivery of natural polyphenols to target tissues and enhance their desirable effects in the cardiovascular system.
  • 546
  • 27 Oct 2020
Topic Review
Taxol Biosynthetic Pathway
Taxol is one of the most effective anticancer drugs in the world that is widely used in the treatment of several cancers. The elucidation of the taxol biosynthetic pathway is the key to solve the problem of taxol supply. So far, the taxol biosynthetic pathway has been reported to require an estimated 20 steps of enzymatic reactions, and most of enzymes involved have been well characterized. In details, the source and formation of the taxane core and the process of the downstream synthetic pathway have been basically depicted, while the modification of the core taxane skeleton has not been fully reported, mainly concerning the developments from diol intermediates to 2-debenzoyltaxane. 
  • 544
  • 01 Jun 2021
Topic Review
Dendrimers in Biomedicine
Biomedicine represents one of the main study areas for dendrimers, which have proven to be valuable both in diagnostics and therapy, due to their capacity for improving solubility, absorption, bioavailability and targeted distribution. Molecular cytotoxicity constitutes a limiting characteristic, especially for cationic and higher-generation dendrimers. Antineoplastic research of dendrimers has been widely developed, and several types of poly(amidoamine) and poly(propylene imine) dendrimer complexes with doxorubicin, paclitaxel, imatinib, sunitinib, cisplatin, melphalan and methotrexate have shown an improvement in comparison with the drug molecule alone. The anti-inflammatory therapy focused on dendrimer complexes of ibuprofen, indomethacin, piroxicam, ketoprofen and diflunisal. In the context of the development of antibiotic-resistant bacterial strains, dendrimer complexes of fluoroquinolones, macrolides, beta-lactamines and aminoglycosides have shown promising effects. Regarding antiviral therapy, studies have been performed to develop dendrimer conjugates with tenofovir, maraviroc, zidovudine, oseltamivir and acyclovir, among others. Furthermore, cardiovascular therapy has strongly addressed dendrimers. Employed in imaging diagnostics, dendrimers reduce the dosage required to obtain images, thus improving the efficiency of radioisotopes. Dendrimers are macromolecular structures with multiple advantages that can suffer modifications depending on the chemical nature of the drug that has to be transported. The results obtained so far encourage the pursuit of new studies.
  • 536
  • 11 Sep 2020
Topic Review
Roles of the CXCL8-CXCR1/2 Axis in Cancer
In humans, Interleukin-8 (IL-8 or CXCL8) is a granulocytic chemokine with multiple roles within the tumor microenvironment (TME), such as recruiting immunosuppressive cells to the tumor, increasing tumor angiogenesis, and promoting epithelial-to-mesenchymal transition (EMT). 
  • 530
  • 29 Mar 2022
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