Cucumber seeds are the seeds of Cucumber(Cucumis sativus L.) , which include a large number of essential fatty acids, plant sterols, glycosides, volatile oils, as well as Ca, Mg ,and other inorganic elements. The cucumber seed oil has a good UV absorption effect because it is rich in an unsaturated functional group structure. Plant sterol in cucumber seed oil has strong permeability to the skin, which promote skin metabolism and inhibit skin inflammation. β-sitosterol in plant sterols can also effectively protect the peroxide of low-density lipoprotein, so they have an antioxidant effect.

In this study, cucumber seed oil was extracted by Soxhlet extraction method as plant sunscreen, in which cucumber seed oil was used as the main component, an appropriate amount of titanium dioxide was used as an antioxidant.Taking the settling solvent ratio as the index, the orthogonal experiment was designed to determine the prescription composition of the pure matrix. Then the single factor experiments of cucumber seed oil, titanium dioxide and vitamin E were carried out. The effects of three components on UV absorption were investigated by orthogonal experiments, and the optimum formula with cucumber seed oil as the main component was finally determined and verified. In conclusion, our plant sunscreen was produced by cucumber seed oil as raw material instead of hormone. There had no harm to the skin. It has the potential to develop plant sunscreen with cucumber seed oil and provides a reference for the development of plant sunscreen and skin care products.

The World Health Organization (WHO), on March 12, 2020, declared a pandemic state of the global epidemic caused by a new coronavirus, SARS-CoV-2. Identifying the Main protease (Mpro) of SARS-CoV-2 as a drug target led to a speed-up drug design and discovery process. However, an effective algorithm is needed to indicate the activity against (Mpro) during virtual screening. In our studies, we proposed a virtual screening protocol combining molecular modeling and machine learning techniques that will allow us to discover novel inhibitors of SARS-CoV-2 Mpro. Based on results from virtual screening, potential Mpro inhibitors were selected for synthesis and further in vitro evaluation. The effectiveness of small-molecule compounds, derivatives of mono-, di- and tri-heterocyclic azole systems with various substituents of an amine, amide, or ester nature were evaluated in the test for antiviral activity. Compounds were first tested on Vero E6 cells to select non-toxic doses on SARS-CoV-2 infected cells. Next, we studied the anti-SARS-CoV-2 activity of selected compounds on infected Vero E6 cells. The most active compound showed 52.6% inhibition of SARS-CoV-2 replication at the dose of 20 µM. In summary, the application of the proposed virtual screening protocol allowed the selection of new compounds to be used as a starting point for developing SARS-Cov-2 Mpro inhibitors.

The project is co-financed by the Polish National Agency for Academic Exchange (PPN/BIT/2021/1/00056/U/00001), Italian Ministry of Foreign Affairs and International Cooperation Executive Programme of Scientific and Technological Cooperation between the Italian Republic and the Republic of Poland (PO22MO07), JUMC grants N42/DBS/000217, N42/DBS/000303.

Carbonic anhydrases are metalloenzymes that regulate the interconversion of CO₂ and H₂CO₃, a reaction involved in many physiological processes. A disfunction of these enzymes is known to induce many diseases such as glaucoma, epilepsy and cancer. That’s what increased the need to concept new target molecules with inhibitory effects on CAs. The most known compounds that inhibits CAs are sulfonamide-containing molecules, citing valdecoxib, acetazolamide and the antitumor agent lately introduced to phase II clinical trials; the SLC-0111. With an intention to obtain a new potential drug candidate, an analogue of the SLC-0111 compound was designed and synthesized using sulfanilamide, chlorosulfonyl isocyanate and aniline. IR, NMR spectroscopy and EA were used in the characterization of the structure. In order to explore the potentiality of our newly synthesized product to inhibit CAs, a docking simulation was performed on the binding pockets of both carbonic anhydrase II complexed with valdecoxib (pdb: 2AW1) and carbonic anhydrase IX complexed with SLC-0111 (pdb: 5JN3). The new derivative revealed an interesting stability inside the cavities of CA II and CA IX with docking scores of -9.782 and -7.466 respectively, and showed an efficient binding affinity in both cases through the formation of metal coordination with Zn and a hydrogen bond with the Thr199 which is known to be essential for the inhibition. Other significant extra interactions were observed as well with other residues in isoform II. Further, the pharmacokinetics properties and drug likeness were predicted using in silico tools; SwissADME and MolSoft online servers.

PARP1 is a nuclear enzyme involved in DNA repair processes. Since its inhibition causes sensitization to DNA damaging chemotherapy (by the so-called “synthetic lethality”), several inhibitors have been recently developed and exploited for clinical use. However, the emergence of resistance to PARP1 inhibitors increased the interest towards alternative approaches able to interfere with PARP1 activity. In particular, within the promoter region of PARP1 a characteristic, non-canonical (3+1) G-quadruplex-forming sequence was identified. A strong correlation between G-quadruplex stabilization in gene promoters and transcriptional regulations has been proposed for several oncogenes. Since no PARP promoter modulators have been described so far, the interaction with a small collection of G-quadruplex binders was investigated, taking into account the particular hybrid topology of PARP1 G-quadruplex. Six structurally diverse compounds, extensively studied and known for showing great affinity towards canonical G-quadruplex, were selected, and NMR, CD, and fluorescence titration studies were carried out. The results from the physico-chemical analyses, confirmed by molecular modelling, showed that only one of the tested compounds showed strong stabilization of the nucleotide, demonstrating that the structural requirements for an optimal interaction between each of the ligands and the peculiar hybrid G-quadruplex region are quite strict. Overall, the studied compounds can be considered as a starting point for the identification of the key features necessary for a selective interaction with the PARP1 promoter G-quadruplex.

Methylphenidate (MPH) and amphetamine (AMPH) increase monoamine levels in the synaptic cleaft, due to their properties and similarities to monoamine neurotransmitters. Stroke and traumatic brain injury, common neurological diseases, affect millions of people every year. Their treatment mainly focuses on the focal point and symptoms, lacking on the curative measures and neural repair. In in vitro and in vivo models, MPH and AMPH showed to promote neuronal recovery following injury through neurite outgrowth.

Thus, this study evaluated the neurite outgrowth and synaptogenesis promoted by clinical relevant concentrations of AMPH and MPH in a neuronal human model, differentiated SH-SY5Y. The cells were exposed to 0.001, 0.01, 0.1, 1 and 10µM of drugs for 24h. Our results reveled that after 24h, AMPH and MPH were not cytotoxic to differentiated SH-SY5Y, by either the MTT reduction or the NR uptake assays. Also, the concentrations of 0.1 and 0.01µM did not affect the expression of synaptophysin, PSD95 and GAP43 evaluated by Western blotting. Moreover, neurite outgrowth was evaluated in microphotographs resourcing to the NeuronJ software and no enhancement of neurite outgrowth in differentiated SH-SY5Y cells was promoted by AMPH or MPH at the concentrations of 0.1 and 0.01µM.

As far as we know, this is the first study evaluating the effect of clinical relevant concentrations of MPH and AMPH in a paradigm of acute exposure to neuronal SH-SY5Y cells, being the starting point to our strategy to understand the possible effects of MPH and AMPH on the improvement of neural network.

Conventional anticancer therapies present low specificity, leading to several secondary effects. To improve these drawbacks, aptamers able to fold into G-quadruplex (G4) are being used to promote drug accumulation in cancer cells. AS1411 is a G4 aptamer able to recognize nucleolin, a protein overexpressed in cancer cells’ surface. This aptamer was tested in clinical trials but showed low response rates and suboptimal pharmacokinetics. Nevertheless, AS1411 is being used as targeting agent. Moreover, AS1411 derivatives were developed, with improved toxicity and high affinity to nucleolin. Thus, we propose to use AT11, an AS1411 derivative, to functionalize liposomes and improve the selectivity of C₈ (a potential anticancer drug) into oral cancer. Therefore, we produced liposomes (blank or C_8-associated) by ethanol injection method to, then, functionalize with AT11-TEG-Cholesteryl. The resulting liposomes were characterized by DLS. C₈ association was determined by UV/vis spectroscopy and the AT11 functionalization was determined by SDS-PAGE. The effect of blank and C_8-associated liposomes on oral cancer and healthy cells’ viability was determined by MTT and its internalization of was visualized by confocal microscopy. Liposomes with hydrodynamic diameters of 148-168 nm were obtained and C₈ was efficiently associated (~100%). When the cells were treated with blank liposomes, cell viability was almost unaffected. After treating with C₈-associated liposomes, both cell lines showed a dose-response effect. Additionally, we observed that AT11-liposomes can internalize and reach the cytoplasm of cells. Overall, these findings suggest that the tested liposomes are promising drug carriers for oral cancer therapy.

The design of peptidomimetic small molecules, such as amino acid substituted xanthones, has become an attractive research field. The strategy of linking molecules with xanthone scaffold to peptide moieties demonstrated to be successful for the development of new antimicrobial agents. Our group has already described xanthones as promising antimicrobials, and as inhibitors of antimicrobial resistance mechanisms. Enantioselectivity studies associated with biological activities were also performed by us, and for some chiral derivatives of xanthones (CDXs) differences were found for the respective enantiomers. Herein, a small library of CDXs was synthesized and their enantiomeric purity was evaluated by chiral liquid chromatography. Enantiomeric ratio values higher than 99% were achieved. The potential of CDXs as antimicrobial agents, and their application to improve the activity of common antibiotics or to reverse bacterial mechanism of resistance were studied. In addition, to gain a better insight on how the active compounds bind to the bacterial efflux pumps, in silico studies were performed. Hit compounds were suggested and, in some cases, enantioselectivity was evident.

Anxiety and depression are two conditions whose incidence increased in the context of COVID-19. Administration of current therapies based on anxiolytic and antidepressant drugs can result in adverse reactions and even potential dangers in the case of some patients like older adults and elderly patients. Aiming to identify safer treatments, we used molecular docking to screen twenty natural compounds against γ-aminobutyric acid A receptor (GABAA receptor), a major drug target in anxiety, and against serotonin transporter (SERT), a major drug target in depression. The list of compounds included molecules that were previously reported as beneficial in the two conditions. In the case of all molecules, we predicted their drug-likeness, bioavailability and pharmacokinetic profiles. Molecular docking has showed that the top five molecules in terms of affinity for GABAA receptor are luteolin, baicalein, myricetin, chrysin and curcumin. In the case of SERT, the top five ligands resulted to be myricetin, luteolin, curcumin, apigenin and fisetin. According to the predictions performed here, these molecules comply with drug-likeness rules, are bioavailable and non-toxic, present a high intestinal absorption and are distributed to the central nervous system. Our results point toward luteolin, myricetin and curcumin as common ligands for GABAA receptor and SERT, suggesting their beneficial effect in both anxiety and depression.

Obesity is a global disease that has been escalating to epidemic proportions over the past years. A recent report from World Obesity Federation predicts that, in 2030, 1 billion people will be obese. Thus, it is mandatory to develop new therapeutic options that are able to manage and control obesity. One of the most promising research paths is the inhibition of pancreatic lipase (PL), responsible for the hydrolysis of 50 to 70% of total dietary triglycerides. Chalcones are the precursors of flavonoids, consisting of two benzene rings connected by a three-carbon α, β-unsaturated carbonyl structure. The goal of the present work was to evaluate the activity of seven chalcones with hydroxy (OH) and chloride (Cl) substituents, as potential inhibitors of PL. For this purpose, spectrophotometric and fluorometric microanalysis systems were used, based on the enzymatic metabolization of p-nitrophenyl butyrate and 4-methylumbeliferyl oleate, respectively. The obtained results showed that chalcones inhibit PL activity, and that the fluorometric method is able to reach higher inhibition rates with less compound than the spectrophotometric method. These findings bring new insights into the structure design for the modulation of PL, but further studies are still needed to further explore these compounds as potential anti-obesity molecules.

FASN a metabolic oncoprotein overexpressed in multiple cancer and regulates the fatty acid requirement for proliferated cells. Thus, FASN has been proposed as a promising novel target for anticancer drug discovery. Herein we report the de-novo design and synthesis of small molecule FASN inhibitors (CTL) targeting breast and colorectal cancer. The structure-activity relationship studies led to identify CTL-1 and CTL-7 as potent, selective FASN inhibitors had an IC₅₀ 2.5 and 3.0 µM. The CTL-1 and CTL-7 inhibits proliferation of colon cell (with IC₅₀ range of 3-5 µM) in HCT-116, CaCO2 and breast cells MCF-7, MDA-MB-231. However, in non-cancerous cell line HEK-293 the IC50 of CTL-1 and CTL-7 was above 30 µM. Further cell cycle analysis and apoptosis assay of CTL-1 and CTL-7 in HCT-116 cells represents S-phase arrest along with prolong apoptotic effect. The western blot analysis of CTL-1 and CTL-7 establish the FASN pathway participation in causing cell apoptosis. The molecular dynamics simulation studies indicate the high affinity of CTL-1 and CTL-7 against the FASN enzyme.