Alpha-hydroxy acids-AHAs and polyphenols-PPs are natural organic compounds frequently used as good and safe hypopigmentation supstances in dermocosmetics for lightening of dark spots appearing on the skin due to oxidative stress. Therefore, the aim was in vitro analysis of content of these compounds and in vivo investigation of hypopigmentation potential of dermocosmetic cream with extract of wild apple fruit-EWAF (Malus sylvestris fructus, (L.) Mill., Rosaceae). Cream was made with 6% of EWAF (obtained by ultrasonic extraction and ethanol as solvent), as a source of AHAs and PPs, and stabilized by alkyl-polyglucoside emulsifiers. Content of AHAs and PPs into cream was investigated using HPLC analysis, while in vivo hypopigmentation potential was investigated employing the biophysical methods on the skin of healthy volunteers after 7 days of cream application, after artificially induced skin hyperpigmentation using dihydroxyacetone (by measuring melanin index-MI and erythema index-EI). Content of identified AHAs was 252mg/100g of cream (the most common were malic (19.75mg/100g) and lactic acid (21.07mg/100g)), and PPs 1.07mg/100g (phloridzin (0.47mg/100g) and chlorogenic acid (0.41mg/100g)). In vivo investigation revealed good hypopigmentation potential of cream. Application of cream with AHAs and PPs, as active exfoliation agents, induced significant decrease of MI (-20,25±41,61) and decrease of EI (-45,25±23,54). Formulated dermocosmetic cream demonstrated good lightening and anti-irritating effects on skin, probably due to the synergistic effects between identified AHAs and PPs. Cream with organic compounds of natural origin, as active hypopigmentation supstances, might be suitable for possible usage as dermocosmetic product for lightening of skin hyperpigmentation.

Cannabidiol (CBD), a major phytocannabinoid in Cannabis sativa, exhibits diverse therapeutic properties, as demonstrated by in silico, in vitro, and in vivo studies. These properties include antiseizure, anticonvulsant, antiarthritic, cardioprotective, analgesic, anti-inflammatory, antioxidant, antitumor, neuroprotective, antiepileptic, and anticancer effects.

This study describes the ultrasound-assisted extraction, isolation, and characterization of CBD from Moroccan Cannabis sativa resin. The petroleum ether - diethyl ether (PE-DE), methanol (MeOH) and water were used as extracting solvents by increasing gradient polarities. Isolation of CBD was achieved through successive normal silica and C18-reversed phase silica gel column chromatography of the PE-DE fraction. Characterization was conducted using infrared (IR) and nuclear magnetic resonance (NMR) techniques. The antioxidant activity of fractions was assessed by the DPPH assay. Total phenolic content (TPC) and total flavonoid content (TFC) were measured with the Folin-Ciocalteu reagent and aluminum trichloride methods, respectively.

The PE-DE fraction showed the highest TPC (44.91 mg EAG/g), followed by MeOH (28.78 mg EAG/g) and water (5.91 mg EAG/g) fractions. The TFC was also highest in the PE-DE fraction (3.733 mg QuE/g), followed by MeOH (2.140 mg QuE/g) and water (0.167 mg QuE/g) fractions. The antioxidant assay revealed significant activity for PE-DE (IC₅₀ = 62.54 µg/mL) and MeOH (IC₅₀ = 96.12 µg/mL) fractions, compared to the water fraction (IC₅₀ = 252.72 µg/mL). Ascorbic acid (IC₅₀ = 7.088 µg/mL) was used as a control.

In light of Morocco's cannabis legalization, these findings suggest that extracts and pure compounds from Moroccan Cannabis may have potential applications in the medical and nutritional fields.

ABSTRACT

Antimicrobial chemotherapeutic failure as a result of pathogenic resistance stain is great concern across the globe, there is need to search for an effective antimicrobial agent from synthetic sources to overcome emergent of microbial resistant in clinical practice. The phenylhydrazone derivatives were scientifically found to have wide application in area of drug discovery due to their anticancer, anti-tubercular, anti-bacterial and anti-fungal activities.

Five (5) novel (E)-Substituted-N-(phenylhydrazones) derivatives’ were obtained by condensation reaction between substituted acetophenone and substituted phenyl hydrazine through one step reaction, here are the five compounds, HS1 (E)-1-(1-(4-bromophenyl)ethylidene)-2-(2,4-dinitrophenyl)hydrazine),HS2 (E)-1-(1-(4-bromophenyl)ethylidene)-2-(4-nitrophenyl)hydrazine), HS3(E)-1-(4-nitrophenyl)-2-(1-(3-nitrophenyl)ethylidene)hydrazine), HS4 (E)-1-(2,4-dinitrophenyl)-2-(1-(3-nitrophenyl)ethylidene)hydrazine), and HS5 (E)-1-(1-(3-nitrophenyl)ethylidene)-2-phenylhydrazine) and their structural elucidation were established on the basis of FTIR, 1D and 2D NMR spectra and the Insilco prediction of physicochemical properties found within the Lipinski's rule of five and the newly synthesized compounds were subjected to antimicrobial assessment for an in-vitro test evaluation using inhibition zone technique, MIC, MBC and MFC.

Abbreviations:

• MIC: Minimal inhibitory concentration, ZOI; Zone of inhibition, MBC; Minimum Bactericidal concentration, MFC; Minimum Fungicidal concentration, FTIR; Fourier transform infrared, NMR; nuclear magnetic resonance, 1D; one-dimensional, 2D; two dimensional and HS1-5: synthetic hydrazone (symbolic code number)

1-tetralone derivatives are compounds of interest due to their diverse biological properties such as antibiotic, anticancer, antioxidant, antiarrhythmic and central nervous system effects. In this work we present, a kinetic study of the Knoevenagel condensation reaction between 5-methoxy-1-tetralone and glyoxylic acid, catalyzed by sulfuric acid, to produce (E)-2-(5-methoxy-1-oxo-3,4-dihydronaphthalen-2(1H)-ylidene)acetic acid. The reaction was carried out in a batch system at 400 rpm for 24 hours at temperatures of 75, 80 and 85 °C. The yields obtained at these temperatures were 90.30, 93.75 and 94.16%, respectively. The reaction was monitored by TLC and HPLC. For the kinetic analysis, three mathematical methods were used: integral, differential and non-linear regression. The results showed an excellent fit of the experimental data to the pseudo-first-order kinetic model. The kinetic parameters calculated at the studied temperatures were: rate constant k=0.0129; 0.0161; 0.0196 (mL/(mmol*min)), activation energy Ea=43.1014 kJ/mol and pre-exponential factor A=8.4608E+03 (mL/(mmol min)). The desired product was purified by recrystallization and characterized using FTIR, GC-MS, ¹H and ¹³C NMR, confirming its structural identity. Acid catalysis significantly improved the kinetics and efficiency of the Knoevenagel condensation reaction between 5-methoxy-1-tetralone and glyoxylic acid, making it an attractive synthetic methodology for the preparation of this class of compounds.

Emerging diseases such as COVID-19 and those of significant public health concern, like rheumatoid arthritis (RA), asthma, Alzheimer’s and parkinson’s diseases, cause hyperinflammation inducing the expression and activation of the isoenzyme cyclooxygenase 2 (COX-2). COX-2 and 5-lipoxygenase both produce thromboxanes and leukotrienes that induce cytokine expression such as tumor necrosis factor alpha (TNF-α) and interlucins (IL-1ß, IL-6). Therefore, one strategy to combat exacerbated inflammation is to develop molecules that inhibit the COX-2/5-LOX system by coupling NSAID structures with amino acids, peptides, or peptidomimetic compounds. The current research reports the synthesis of hybrid compounds involving 4-(4-methoxyphenyl)-4-oxobutanoic acid, an analog of the NSAID fenbufen obtained through Heck coupling, with the aromatic dipeptides Tyr-Tyr, Phe-Tyr, Tyr-Phe y Phe-Phe. Furthermore, molecular docking studies of the obtained compounds showed binding energies of approximately -11.01 kcal/mol (NSAID-Tyr-Phe), comparable to the reference drug celecoxib and superior to diclofenac. Similarly, the compound NSAID-Phe-Tyr demonstrated a binding energy of -9.2 kcal/mol, which was superior to the reference drug Zileuton. The most successful results revealed stability in the molecular dynamics trajectories executed in NAMD and excellent binding free energies (-33.91 kcal/mol) calculated using gmx_MMPBSA, which enabled a detailed analysis of the energy contribution of each amino acid in the catalytic site.

The last decades have witnessed an increasing interest in advanced electroactive biomaterials based on conducting, π-conjugated polymers for use in different biomedical applications. Recently, we reported about synthesis of an oligothiophene grafted with oligo-(D, L-lactide) (OTh-PDLLA) that has been thought to function as a biolectronic interface, biocompatible and bioerodible.

The present report focuses on the study of those properties of OTh-PDLLA that allow to establishing its suitability as a biomaterial. Thus, its capability for forming thin films, on either rigid or flexible supports, using for processing solvents with different polarities and variable concentrations and films surface properties were explored employing dynamic laser-scattering (DLS), contact- angle measurement and atomic force microscopy (AFM). The obtained results, referring to change in particle’s size, in wettability and films surface topography, have shown that OTh-PDLLA offer several ways to modulate films surface topography properties in order to adjust their interactions with biological entities as proteins or cells. Notably, keeping constant the nature of solvent but varying solution’s concentration the films roughness can be varied, while solvent polarity has more influence in films morphology than in their wettability.The biocompatibility of the OTh-PDLLA films deposited on rigid or flexible substrates was assessed by normal human gingival fibroblasts (NHGF) cells interaction. The obtained results confirm the oligomer’s biocompatibility, advocate for OTh-PDLLA potential as electroactive biointerface or as active layer in flexible and/or implantable transient electronics.

Cholinesterase inhibitors play a crucial role in enhancing cerebral cholinergic activity, fundamental for treating neurodegenerative diseases. An innovative strategy involves enriching these molecules with additional biological properties to develop multifunctional compounds that can offer broader and enhanced pharmacological effects, especially in the treatment of multifactorial pathologies such as Alzheimer's disease.

In previous work, we demonstrated that caffeine-pyrrolidine hybrids can inhibit acetylcholinesterase (AChE) and activate nicotinic acetylcholine receptors (nAChR). Particularly, the hybrid linked by a seven-methylene hydrocarbon chain (caffeine-C7-pyrrolidine) showed the highest potency.

In this study, we synthesized a series of new derivatives by linking a fragment of methylxanthine with a secondary amine using a seven-carbon linker. We used alkyl bromides of theophylline and theobromine as starting reagents, and diethylamine and N-benzylmethylamine as secondary amines. Additionally, we synthesized two new compounds by replacing the methylxanthine fragment with azobenzene (Ph-N=N-Ph), known for its photo-modulable properties. The primary objective of this research was to conduct a structure-activity analysis to assess the impact of the pharmacophore (azobenzene or methylxanthine) and the amino group (diethylamine or N-benzylmethylamine) on biological activity efficacy. All synthesized compounds demonstrated inhibitory capacity against AChE. Among the azobenzene derivatives, the most active hybrid was AZO-C7-DEA ((E)-N,N-diethyl-7-(4-(phenyldiazenyl)phenoxy)heptan-1-amine) with an IC₅₀ of 1.1 µM. Furthermore, among the methylxanthine derivatives, theobromine-C7-DEA (7-(7-(benzyl(methyl)amino)heptyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione) emerged as the most potent inhibitor with an IC₅₀ of 0.188 µM.

In this study, two (2) new methoxy-chalcone derivatives [(E)-1-(2,4-dimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (5a) and (E)-3-(4-methoxyphenyl)-1-(2,4,5-trimethoxyphenyl)prop-2-en-1-one (5b)] were designed and synthesized by condensation reaction of 2,4-dimethoxy acetophenone as well as 2,4,5-trimethoxy acetophenone with 4-methoxybenzaldehyde using NaOH as the catalyst. The products were crystallized with ethanol and dried to constant weight. The percentage yield was calculated. The purity of the samples wereconfirmed using TLC and melting point were determined. The structure of the products were verified on the foundation of FT-IR, proton (1H-NMR). Molecular docking studies were carried out using Auto dock vina of pyrex to predict its antimicrobial potentials, and the docked compound was visualized using discovery studio visualizer. The receptor (Bacteria DNA gyrase) was obtained from protein data bank (PDB) with I.D of (4DUH). Compound 5a had binding energy of (-7.6kcal/mol) while compound 5b had (-7.0kcal/mol). The two compound exhibited good molecular interaction with receptor, which include the hydrogen bonding and hydrophobic interactions. The result from this work shows that both compounds had good binding affinity to the receptor, and are predicted to inhibit the bacteria DNA gyrase. Compound 5a had showed to have superior activity when compared to compound 5b. The compounds haveexhibited great potentials to serve as a lead for the development of novel antimicrobial agents.

The threatening phenomenon of antibiotic failure in the future determines the intensive research of antibacterial active compounds to be promising candidates as antibiotics. Quinolines with only representative in clinical practice – Nitroxoline^TM are, in addition to successful beta-lactams, macrolides, tetracyclines and other antibiotic categories forgotten antibiotics. The perspective the antibacterial efficiency of Nitroxoline^TM and 2-aminoquinolin-8-ol on eight selected, the most problematic, highly resistant bacterial species (Klebsiella ssp., Enterococcus ssp., Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus) could lead to higher solubility and thus bioavailability and increasing of antibacterial effect. In the first phase, basic salts of Nitroxoline^TM with sodium hydroxide, benzylamine, 4-(aminomethyl)pyridine and other primary amines were synthesized. Within the second phase, opposite acidic salts of 2-aminoquinolin-8-ol were synthesized with following acids: oxalic acid, pyrazine-2,3-dicarboxylic acid, chelidonic acid, quinaldic acid, 3,5-dinitrosalycilic acid, pyridine-3,4-dicarboxylic acid, quinoline-2-carboxylic acid, quinoline-3-carboxylic acid, kynurenic acid, xanthurenic. Nitroxoline^TM and 2-aminoquinolin-8-ol both expressed flat antibacterial effect with average value on eight mentioned bacterial strains: 6,1 mg/L (32 mM), respectively 14,2 mg/L (88 mM). The synthetized salts of both quinolinols expressed significantly higher solubility and slightly increased antibacterial activity. The identity and purity of prepared products were determined by NMR and IR spectroscopy. The MW values of both quinolinols are relatively low and offer better use of the largest molecule limit, defined by Lipinski´s rule of five at 500 g/M. The options of the choice of amines or acids offers the achievement of quarternary salts with improved antibacterial activity.

Avenanthramides (AVNs) means a unique secondary metabolites category, produced exclusively by genus Avena sp. Till nowadays it was described more than eighty. AVNs are amides of anthranilic acid and various polyphenolic acids with one or more double bonds. AVNs as single molecules express strong antioxidant, anti-inflammatory and antineoplastic effect. Taking in account limited largest of the AVNs molecules (to 300 g/M) it is possible to expect increase of biological activity by dimerization or derivatization, where we could categorize too preparation of nanoparticles by green synthesis techniques, what is significant subject of current research. For green synthesis it is necessary the selection of the oat extracts with maximal AVNs content, ideally AVNs with predicted optimal pharmacological parameters and significant activity. The optimal varieties were selected from bulky collection with n> 100, the dynamic of the secondary metabolites synthesis during germination process was detailly monitored in case of variety TATRAN during ten days by HPLC techniques. The maximal content of AVNs was archived on the 8-th day of germination for variety TATRAN, 610.13 mg/g of dried material. For major AVNs (2c, 2p, 2f) was realized quantification by external calibration, other AVNs were analyzed semi- quantitively. Selected water-methanolic extracts with perspective AVNs content were subjected to preparation of green synthesis products by reaction with AgNO₃. For synthetized products were realized basic, spectral analysis and compared was antioxidant and pro-oxidant activity towards basic extracts. The archived results show statistically significant increase of pro-oxidant activity, what is one of the mechanisms of antimicrobial and cytostatic effect.