Ligand and Structure-Based Virtual Screening in Combination, to Evaluate Small Organic Molecules as Inhibitors for the XIAP Anti-Apoptotic Protein: The Xanthohumol Hypothesis.

Herein, we propose two chalcone molecules, (E)-1-(4-methoxyphenyl)-3-(p-tolyl) prop-2-en-1-one and (E)-3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl) prop-2-en-1-one, based on the anticancer bioactive molecule Xanthohumol, which are suitable for further in vitro and in vivo studies. Their ability to create stable complexes with the antiapoptotic X-linked IAP (XIAP) protein makes them promising anticancer agents. The calculations were based on ligand-based and structure-based virtual screening combined with the pharmacophore build. Additionally, the structures passed Lipinski's rule for drug use, and their reactivity was confirmed using density functional theory studies. ADMET studies were also performed to reveal the pharmacokinetic potential of the compounds. The candidates were chosen from 10,639,400 compounds, and the docking protocols were evaluated using molecular dynamics simulations.

Metal-based complexes against SARS-CoV-2.

The first appearance of SARS-CoV-2 is dated back to 2019. This new member of the coronavirus family has caused more than 5 million deaths worldwide up until the end of January 2022. At the moment, and after intensive vaccination programmes throughout the world, the pandemic is still active, whilst new mutations constantly appear. Researchers are working intensively to discover antiviral drugs to combat the severe cases in intensive care units, giving the overloaded hospital units a breather. Alongside various research projects focusing on developing small pharmaceutical molecules, a significant proportion of the research community has shifted towards paying attention to metal drugs. In this small review, we make brief reference to the use of metal drugs in therapeutics and provide some examples of metal drugs that are of extreme interest in the current pandemic. At the same time, we will also examine some of their promising mechanisms of action and possible effectiveness against COVID-19.

NGIWY-Amide: A Bioinspired Ultrashort Self-Assembled Peptide Gelator for Local Drug Delivery Applications.

Fibrillar structures derived from plant or animal origin have long been a source of inspiration for the design of new biomaterials. The Asn-Gly-Ile-Trp-Tyr-NH2 (NGIWY-amide) pentapeptide, isolated from the sea cucumber Apostichopus japonicus, which spontaneously self-assembles in water to form hydrogel, pertains to this category. In this study, we evaluated this ultra-short cosmetic bioinspired peptide as vector for local drug delivery applications. Combining nuclear magnetic resonance, circular dichroism, infrared spectroscopy, X-ray diffraction, and rheological studies, the synthesized pentapeptide formed a stiff hydrogel with a high ß-sheet content. Molecular dynamic simulations aligned well with scanning electron and atomic-force microscopy studies, revealing a highly filamentous structure with the fibers adopting a helical-twisted morphology. Model dye localization within the supramolecular hydrogel provided insights on the preferential distribution of hydrophobic and hydrophilic compounds in the hydrogel network. That was further depicted in the diffusion kinetics of drugs differing in their aqueous solubility and molecular weight, namely, doxorubicin hydrochloride, curcumin, and octreotide acetate, highlighting its versatility as a delivery vector of both hydrophobic and hydrophilic compounds of different molecular weight. Along with the observed cytocompatibility of the hydrogel, the NGIWY-amide pentapeptide may offer new approaches for cell growth, drug delivery, and 3D bioprinting tissue-engineering applications.

Screening possible drug molecules for Covid-19. The example of vanadium (III/IV/V) complex molecules with computational chemistry and molecular docking.

We are still facing a Covid-19 pandemic these days and after the aggressively infection control measures taken by the governments in the whole world, there is a need of a rapid pharmaceutical solution in order to control this crisis. The computer aided chemistry and molecular docking is a rapid tool for drug screening and investigation. Moreover, more metal-based drugs are tested daily by research institutes for their antiviral activity. Here, we make use of theoretical studies on previously published biological active complex molecules of vanadium as an example of evaluating possible drug candidates before entering the laboratory. We used DFT calculation studies for structural elucidation and optimization of the molecules and molecular docking studies on several Covid-19 related proteins. Our findings suggest that drug discovery should always be computer -aided. Additionally, it is found that Vtocdea and VXn molecules are seem to be good candidates for further studies as antiviral agents.

Cell Arrest and Apoptosis Induced by the Next Generation of Vanadium Based Drugs: Action Mechanism to Structure Relation and Future Perspectives.

BACKGROUND: Every year, we encounter more projects indicating the promising anticancer activity of vanadium molecules against different types of cancer cells. The new generation of metal-based drugs, targets the energy supplies of the cell through ROS generation leading them to cell arrest and apoptosis. The relatively low toxicity of vanadium metal, the different oxidation states that it can occur and in general, the lipophilicity of transition metals, gave attention to vanadium after the exhausting research in platinum-based drugs. Herein, the latest advances in the apoptotic activity of vanadium complex molecules have been reviewed and revealed the structure to action relationship. Future perspectives of vanadium anticancer drugs are also discussed. METHODS: Data were collected from Web of Science, Scopus, Pubmed, through searching of these keywords: "apoptosis", "anticancer drugs", "vanadium complexes", "synthesis" and "cell arrest". RESULTS: A good amount of vanadium complexes gave promising results over the past few years, showing that a more careful approach of a ligand design could give rise to the next generation of vanadium drugs. CONCLUSION: The low toxicity of vanadium ion in combination with its V(IV) species selectivity gives the vanadium a head starts against other transition metal complexes.