For several years, ferrocene moiety represents a significant part of the structure of different biologically active compounds. Ferrocene is stable and non-toxic compound and as such very useful for various syntheses. The combination of pharmacologically active N-heterocycles with ferrocene mostly leads to a favorable change in biological properties in a huge number of drugs. Considering the importance of these properties, this article describes the synthesis and characterization of a new series of ferrocenyl pyrazolines in good yields. Screening of the new products in vitro against human cervical cancer cells (HeLa), human breast cancer cells (MDA-MB-231), human colon cancer cells (HCT-116), and human fibroblast (MRC-5, as control cells) by the MTT method was performed.

Angiotensin-converting enzyme (ACE) inhibitors are anti-hypertensive drugs associated with several side effects. Natural compounds, namely bioactive peptides from brewing by-products – brewers' spent grain (BSG) and yeast (BSY) – are promising alternatives since they can inhibit ACE in vitro and are less likely to cause severe side effects while maintaining the therapeutic efficacy. However, the impact in peptides’ bioavailability after oral administration have not been assessed so far. Thus, the aim of this study was to understand in vitro the impact of the oral route on the effectiveness of BSG/BSY peptides as ACE inhibitors. Extracted BSG/BSY proteins were hydrolysed and sequentially subjected to simulated gastrointestinal digestion (INFOGEST), intestinal absorption and liver metabolism (co-culture of Caco-2 and HepG2 cells). MTT assay was used to assess BSG/BSY peptides safeness. The ACE-inhibitory potential of initial and final products (BSY, BSG and a mixture 50:50 - MIX) at identical concentration (0,857mg/mL) was measured (fluorometric assay) and compared with Captopril (1µM, a clinically used ACE-inhibitory drug). Simulation of oral administration increased brewing peptides’ ACE-inhibitory capacity. When comparing the final peptides with captopril, BSY demonstrated identical potency, while BSG showed 22% greater efficacy, and the new tested product MIX presented 30% higher inhibition. In conclusion, the current study shows that BSG, BSY and MIX natural peptides derived from the brewing industry enhance their bioactive properties as ACE-inhibitors after oral administration, validating the usefulness of these peptides to reduce the risk, ameliorate or treat primary hypertension.

CP-225917 is isolated from unidentified fungi, which exhibited farnesyl transferase and squalene synthase inhibitory activity. In the present investigation, computational studies including, docking, molecular dynamic simulations, protein ligand interaction fingerprints (PLIF) analysis and pharmacokinetic properties calculations were performed on the molecule. The crystallographic structure (pdb id 3E37) was used for the docking and MD simulation studies and it provided the docking score of -11.3 and FTase inhibitory activity of IC₅₀ = 6000 nM. Further the conformational analysis studied on different conformations obtained from the MD simulations and PLIF analysis showed that the compounds has significant interaction with Lys164, Tyr166, His201, ArgB202, HisB248, TyrB300, LysB356, TyrB361, HisB362 and ZnC1001 residues in the chain A and B of the protein. However, the MD simulations revealed that the molecules has major interactions with the residues in the B chain of the FTase enzyme. The tyrosine residues (TyrB300 and TyrB361) are forming surface and side-chain acceptor interactions and the residue (TyrB361) has interaction fingerprint on the backbone acceptor and donor interactions. The histidine residues exhibited hydrogen bonding interaction and LysB356 has ionic interactions. The Zn metal showed ionic interaction with the ligand molecules for the activity. The Molecular Dynamics simulations of the complexes showed significant RMSD and RMSF values within the limit revealed that the complex is stabilized with the residues. These computational studies and the reported biological activities of the compounds showed that this compound may be used as lead compounds to develop novel FTase inhibitors.

The multi-resistant opportunistic bacterium Pseudomonas aeruginosa has been identified by the WHO as one of the most threatening pathogens of our time, and a priority for the development of new treatments. Biofilms produced by this micro-organism act as protective barriers. They increase both its pathogenicity via a persistence towards the immune system and its resistance to antibiotics. Biofilm formation is coordinated by the Quorum Sensing (QS) that is a bacterial communication network responsible for virulence pathways expression according to the population density. In P. aeruginosa specific QS system pqs, the transcription factor PqsR regulates the activation of virulence-related genes via recognition of its auto-inducer PQS (Pseudomonas Quinolone Signal). This circuit stimulates the secretion of virulence factors like pyocyanin as well as the establishment of biofilms. Therefore, the development of non-bactericidal agents that disrupt QS connections appears as a promising alternative to conventional medicines, without creating selection pressure issues. These new anti-virulence agents (AVAs) could restore the efficacy of antibiotics when used in combination therapy. In particular, the design of AVAs that inhibit PqsR appears to be a sustainable approach to combat P. aeruginosa specifically. Bi-aromatic PqsR inhibitors possessing a 4-aminoquinoline moiety have been described in the literature. Meanwhile, our team recently discovered a series of 2-heteroaryl-4-quinolones that display interesting anti-biofilm and anti-pyocyanin activities. We now aim at developing a family of 2-heteroaryl-4-aminoquinolines as new AVAs potentially inhibiting PqsR. The synthesis as well as the physicochemical and biological evaluation of those novel molecules will be described in the poster.

Heterocycles play an important role in therapeutic chemistry. Currently, more than 85% of all biologically active molecules contain at least one heterocycle. The FDA (Food and Drug Administration) database reveals that 14% of active ingredients containing a nitrogen heterocycle are pyridines, mainly mono- or di-substituted. Therefore, the study of mono-, di-, and tri-substituted pyridine’s reactivity is important in the development of new biologically active molecules. In this study, we focused on a particular family of pyridines: 2-pyridinecarboxaldehydes. The latter are often obtained by oxidation of the corresponding 2-methylpyridines. However, these reactions usually require the use of dangerous reagents such as oxygen, or expensive catalysts.

Oxidation reactions are very common in organic chemistry, but aldehydes can be susceptible to overoxidation to carboxylic acids. It is therefore essential to develop and optimise oxidation conditions to limit this undesirable subproduct. In our laboratory, we have developed a method for oxidation of various 2-methylpyridines to their 2-pyridinecarboxaldehyde analogues, whereas limiting overoxidation. This method led to better yields than those described in the literature, while simplify the operating mode.

The 1,2,3-triazole ring has been gaining increased attention in Medicinal Chemistry over the past years since it has been associated with metabolic stability and several biological activities, including antifouling. Therefore, the hybridization of this heterocycle with other pharmacophores which showed ability to prevent marine biofouling can be a strategy to obtain more effective and stable compounds. Marine biofouling remains a huge challenge for maritime industries and public health, causing economic, human, and ecological concerns, with few environmentally safe options to prevent this phenomenon. Considering that the incorporation of an acetophenone into coatings was found to decrease the attachment of marine micro and macroorganisms, and in an attempt to obtain new effective acetophenone derivatives, a series of triazolyl acetophenones were obtained, through hybridization with 1,2,3-triazole ring and other pharmacophores, using the copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) methodology. Fourteen new acetophenone-1,2,3-triazole hybrids were obtained and the screening against the settlement of the macrofouling mussel Mytilus galloprovincialis and on five biofilm-forming marine bacteria allowed to identify promising compounds. Three compounds were able to inhibit the growth of marine bacteria Roseobacter litoralis, while other three compounds significantly inhibited the settlement of mussel larvae. For those, the ability to inhibit the growth of Navicula sp. microalgae was also evaluated. One acetophenone was found to display complementary antifouling activity against macrofouling mussel and microalgae Navicula sp. The most potent compounds also showed to be less toxic to the non-target species Artemia salina than the commercial biocide Econea®.

Plectranthus is a well-known genus belonging to Lamiaceae family and mainly distributed in tropical areas of the globe. Furthermore, Plectranthus species are particularly rich in phenolic compounds and abietane-type diterpenes, such as royleanones, widely used in traditional medicine against a vast range of diseases, including skin disorders and cancer.

In order to study the phytochemical composition and the biological activity of P. ecklonii Benth., ultrasound-assisted extractions were carried out using methanol and acetone as solvents.

It is known from literature data that phenolic compounds are predominant in the methanol extracts, while the phytochemical analysis of the acetone ones from our research group evidenced abietanes as the most occurring secondary metabolites.

Methanol extracts were screened to assay their potential bioactivity as antimicrobials, antioxidants and on skin-related enzymes, as well as their general toxicity. The results showed only a moderate effect against bacteria, but a very promising antioxidant activity, and no relevant general toxicity. Good tyrosinase inhibition was observed, together with an excellent inhibitory activity on collagenase, making the methanolic extract a promising raw material to be used for the development of dermocosmetic formulations, especially those with antiaging activity. Fractionation and further purification were carried out on the acetone extracts, highlighting a significant cytotoxic activity, mainly due to the presence of diterpenes, with an observed IC₅₀ in the low-micromolar range.

Considering the potential applications for internal and topical uses, further studies are currently ongoing on both the extracts to investigate about other relevant biological activities and ascertain their safety.

Quercetin is a polyphenolic flavonoid with recognized strong antioxidant potential, which can prevent and treat several diseases. Hybrids containing a heterocyclic 1,2,3-triazole have shown promising biological properties, such as anticancer, anti-Alzheimer’s, among others. The hybridization of these two entities can allow the discovery of new molecules with more potent biological properties.

Novel quercetin-1,2,3-triazole hybrids were prepared in good to excelent yields via Cu(I)-catalyzed azide-alkyne cycloaddition reaction under microwave irradiation. These new hybrids contain a 1,4-disubstituted 1,2,3-triazole ring at the 3-OH position of quercetin whilst the remaining hydroxyl groups were either protected as methyl or benzyl groups or left unprotected.

All the quercetin-1,2,3-triazole hybrids I–IV were tested on REM-134 canine mammary cancer cell line, which is commonly used as a translational model for human breast cancer. These new analogues exhibit potent antiproliferative activity against this cancer cell line. The results show that some of these new quercetin-1,2,3-triazole hybrids have better activity than quercetin itself. Our best inhibitors displayed IC₅₀ values in the range of 41–180 nM, which will be a promising contribution for treatment of both canine and human breast cancer.

Molecular dynamics (MD) is a powerful tool used to study the evolution of molecular systems and predict their properties from the inherent interactions. GROMACS is a famous tool for MD and developed as open-source software. GROMACS is run from the command line with user-provided configuration files. However, the absence of a graphical user interface (GUI) of GROMACS and proper protocol to develop the input files (Ex: itp files, topology files, etc.) prevent the researcher from visualizing the MD trajectory in a real-time manner as well as addressing the structural problem. This issue was addressed by developing a graphical user interface of GROMACS as plugins for YASARA molecular graphics suite, called YAMACS. YAMACS is an open-source project and is available on GitHub (https://github.com/YAMACS-SML/YAMACS). The tool can perform MD simulations for protein, protein-ligand complex, membrane–protein complex, membrane-protein complex, and small molecule system. Easily YAMACS automatizes several steps of input file preparation and allows visualizing MD trajectory in real-time.

At this conference, I will present the application of YAMACS to simulate the complex sphingomyelin/POPC embedded in a membrane of POPC. I will also introduce a collaborative platform to create an open community of users and developers, extend the functionalities of YAMACS and improve the quality of computational drug design studies.

UV radiation promotes the generation of reactive oxygen (ROS) and nitrogen (RNS) species resulting in skin damage. Cosmetic industries have adopted the strategy to incorporate antioxidants in sunscreen formulations, aiming to prevent/minimize the UV-induced oxidative damage, boost photoprotection effectiveness and to mitigate skin photoaging. This work aims to characterize the frequency of the use of antioxidants in commercial sunscreens. Photoprotective formulations currently marketed in parapharmacies and pharmacies were analysed concerning the composition described on the label. As a result, pure compounds with antioxidant activity were found. The majority of the sunscreen formulations contained antioxidants and the most frequently used were vitamin E and derivatives. A more thorough analysis of these antioxidants is also provided, unveiling the top of the antioxidant ingredients found in sunscreens and their mechanisms of action. A critical appraisal of the scientific evidence regarding their effectiveness is also performed. In conclusion, this work provides an up-to-date overview about the use of antioxidants in commercial sunscreens for a better understanding of the advantages associated to their use in photoprotective formulations.