Plectranthus genus (Lamiaceae) is known to be rich in bioactive abietane royleanone-type diterpenes, such as the 6,7-dehydroxyroyleanone (1). This abietane royleanone 1 can be isolated from P. madagascariensis (var. aliciae Codd) essential oil and present cytotoxic activity against several cancer cell lines. Moreover, 1 has one hydroxyl group that offers an opportunity for derivatization, which can be strategically explored to increase the cytotoxic potential of lead compound 1. Considering this, the aim of the present work was to explore the obtention of 1, from P. aliciae (Codd) van Jaarsv. & T.J.Edwards., a subspecies of P. madagascariensis. to be further used in the preparation of new ester derivatives with enhanced biological activities. A hydrodistillation using Clevenger equipment was performed on P. aliciae leaves, to afford the essential oil (EO). Royleanone 1 was assessed as the major compound of the EO, by HPLC-DAD. Furthermore, compound 1 was isolated and used as a scaffold for esterification reactions. It was possible to synthesize three new acyl derivatives (2 to 4), with overall good yields (86 - 95 %). Regarding the biological activity screening, all the semi-synthetic derivatives (2-4) improved the antioxidant activity and the cytotoxicity in MCF-7 and NCI-H460 human cancer cell lines, when compared to the parent compound 1. Notably, the new esters (2-4) showed promising anti-inflammatory activities, in a range of 16 to 53 times higher than 1 and surpassed the positive control dexamethasone. Currently, the mechanism of action and safety of the potential anti-inflammatory derivatives are under evaluation.

Oxidative stress is a concept used to describe the condition of oxidative challenges resulting from the critical imbalance between free radical generation and antioxidant defences. Oxidative stress, arising as a result of an imbalance between free radical production and antioxidant defences, is associated with damage to a wide range of molecular species including lipids, proteins, nucleic acids and red blood cells. Necessitating the need to explore natural plants in search of compounds with antioxidant activity. The study was designed to evaluate the in vitro and in vivo antioxidative and anti-hyperglycemic potentials of bran and bran oil of Faro 60 (Jamila Rice). The rice bran and oil demonstrated a significant free radical scavenging activity as it scavenges hydrogen peroxide radical with values 82.77±0.42 mg/mL and 95.26±0.07 mg/mL respectively when compared with the standard vitamin C, which scavenges with 70.17±0.06 at 20 mg/mL. Furthermore, rice bran oil demonstrated anti-diabetic effects in vitro, inhibiting alpha-amylase activity at 35.65±10.10% when compared with acarbose at 20.83±2.71% at a concentration of 20 mg/mL. More so, rice bran oil was able to lower the effect of lipid peroxidation in the plasma, liver and kidney of diclofenac-induced oxidative stressed mice at 3.22±3.70, 4.87±2.43 and 4.88±3.61 µmole/mg protein when compared with the normal control 3.32±4.07, 6.13±1.05 and 6.94±4.69 µmole/mg protein respectively. The rice bran oil significantly (p<0.05) lowered blood sugar levels during the oral glucose tolerance test. The rice bran and rice bran oil demonstrated significant free radical scavenging and anti-hyperglycemic activities both in vitro and in vivo. It could be utilized as a good source of natural antioxidants.

Burns are traumatic pathologies responsible for significant morbidity and mortality, which is considered as a public health problem, particularly due to their frequency, potential severity, the side effects they can cause as well as their treatment and prevention. In fact, according to the World Health Organization (WHO), approximately 11 million people suffer from burns each year and 180,000 deaths are due to these injuries. Although the development of modern medicine has resulted in the coming of innovative drugs and procedures, the problem of accelerating healing with the least possible side effects still remains in addition to socio-economic and cultural reasons which are added to that. A renewed interest in medicinal plants as well as traditional medicine for curative purposes is currently being observed to treat burns. It is in this context that our study takes place, the essential objective of which is to evaluate the potentially healing and toxicological effect of crude Urtica dioica leaves extract through an in vivo study while exploring a possible antibacterial effect of this plant. Our results demonstrated the safety of ethanolic extract of nettle, in fact, the evaluation of acute toxicity of Urtica dioica ethanolic extract revealed no mortality or morbidity of female albino Wistar rats treated topically with single doses of extract (1 g/kg, 2 g/kg and 5 g/kg). During the 14 days of observations, no sign of intoxication or physiological change in the animal was recorded. The use of nettle leaf extract on 3rd degree thermal burns inflicted on male Wistar rats showed significant anti-inflammatory and healing activity, as well as a proliferative effect on hairs through activation skin hair follicles compared to untreated groups. However, no antibacterial activity of nettle extract was observed with the type strains tested. It can be concluded that the extract of our plant has remarkable healing effects with non-toxic effect on the organism.

Thymol, a naturally occurring monoterpenoid phenol, has sparked attention for its potential therapeutic properties, including antioxidant and antibacterial activities. In this study, I emphasized synthesizing azo derivatives of thymol and evaluating their molecular docking, antioxidant, and antibacterial properties. The synthesis involved the chemical modification of thymol to create azo compounds, followed by computational docking studies to predict their potential binding affinity towards specific target proteins. A total of nine azo derivatives of thymol have been synthesized from different substituted aromatic amines and characterized by IR and proton NMR. The antioxidant activity of the synthesized azo derivatives was assessed using a DPPH assay, highlighting their potential as free radical scavengers. Furthermore, the antibacterial properties of the derivatives were evaluated against Staphylococcus aureus and Escherichia coli to assess their potential as antimicrobial agents. Additionally, drug-like properties of derivatives were evaluated using bioinformatic tools such as PASS prediction, molecular docking, and Lipinski rules of five, as well as toxic nature and LD₅₀ values. All nine compounds exhibited significant antibacterial action, with one showing strong antioxidant activity. Furthermore, the docking scores of derivatives fell between 124 to 106 (LibDock score) against two bacterial targets. The findings of this work provide important insights into potential applications of thymol azo derivatives as multifunctional molecules with antioxidant and antibacterial properties, necessitating additional research into their potential therapeutic usage.

Abstract: Aggregation of alpha-synuclein into fibrils and their deposition in Lewy-bodies is a characteristic hallmark of Parkinson’s disease, multiple system atrophy and various other neurodegenerative diseases. Better understanding of the spatiotemporal development of these aggregates would greatly facilitate diagnosis and therapy development and is thus desperately awaited. However, despite great efforts from different research groups in academia and industry no PET tracer for synuclein has reached clinical application yet. The need for high selectivity and optimal pharmacokinetic properties due to frequent presence of Aß and Tau co-pathologies, the intracellular localization and the low abundance of the target are critical challenges in the development of synuclein PET tracers. We are currently pursuing several libraries on independent scaffolds and assessing their binding to recombinant synuclein, Aß and Tau in direct or competitive assays. Automated radiolabeling procedures with ¹⁸F or ¹¹C at high specific radioactivity are developed for promising tracer candidates. Furthermore, the compounds’ binding to human brain slices harboring defined pathology is measured using in vitro autoradiography. Blood-brain barrier penetration, pharmacokinetics and metabolism are assessed in healthy mice to ensure suitability for brain imaging with low non-specific retention. Using this strategy, we were able to achieve a diverse set of radiotracers with promising characteristics. While most of the compounds in literature suffer from suboptimal selectivity, we were able to identify a candidate with virtually absent Aß binding in our in vitro competition assay. While the pharmacokinetics of this candidate will need further optimization, the obtained data represent a promising starting point for future work.

Schinus areira L., commonly known as "Aguaribay" or "Molle", belongs to the family Anacardiaceae. This plant from the southwest of the province of Buenos Aires, Argentina, is used in traditional medicine, and known for several important biological actions. Butyrylcholinesterase (BChE) may represent an important therapeutic target for Alzheimer Disease (AD), and the search for new dual AChE (acetylcholinesterase) and BChE inhibitors is mandatory to find new alternative treatments for AD patients that do not respond to selective AChE inhibitors. The aim of this work is to evaluate the inhibition of cholinesterase enzymes by the essential oil of Schinus areira. The chemical composition of the essential oil (EO) obtained from the aerial parts by hydrodistillation was determined by gas chromatography-mass spectrometry (GC-MS). AChE and BChE inhibition were determined spectrophotometrically by Ellman’s method. A bioguided fractionation of the EO was performed using different chromatographic techniques (preparative and thin layer chromatography, silica gel column chromatography) to achieve the isolation of the active components. The EO, containing α-phellandrene, camphene, α-pinene and β-eudesmol as major components, showed more effective BChE inhibition (IC₅₀ = 42.37 µg/mL) compared to AChE inhibition (IC₅₀ = 347.3 µg/mL). The isolated compounds β-eudesmol and α-phellandrene showed potent BChE inhibition (IC₅₀ = 11.6 - 19.8 µM) and moderate AChE inhibitory activity (IC₅₀ = 65.63 – 84.54 µM). These results suggest that the EO of S. areira could be a source of bioactive compounds that may be of interest for the development of potential new alternatives in the treatment of AD

Santolina chamaecyparissus (SC) and Ambrosia peruviana (AP) (Asteraceae) are aromatic plants cultivated at the southwest of Buenos Aires province, Argentina, commonly known as camomile and camphor, respectively. The medicinal properties of these species have been extensively investigated and their therapeutic actions have been attributed to certain sesquiterpenes components. In this work we focus our attention on the dichloromethane extract (DCME) of these plants and its bioactive components. These sub-extracts were analyzed by GC-MS and fractionated by silica gel column chromatography. The isolated active compounds were identified by comparing their ¹H and ¹³ C NMR data with those reported in the literature. The active compounds obtained from DCME-SC were identified as manool and α-bisabololol, while dehydroaromandendrene and germacrene B were isolated from DCME-AP. DCME-SC, DCME-AP and the active isolated compounds showed potent antioxidant activity by scavenging free radicals. Good acetylcholinesterase (AChE) inhibition results were also observed for DCME-SC and DCME-AP with IC₅₀ values of 60.25 and 68.21 µg/mL, respectively. Compounds isolated from DCME-SC presented a potent inhibition of AChE with IC₅₀ values in the range 6.04 - 14.96 µM, while the compounds isolated from DCME-AP presented inhibition with IC₅₀ values between 27.12 and 33.89 µM. These results suggest that this plants and/or their components could lead to the development of new anti-Alzheimer agents.

Cancer is a major challenge for Public Health, being one of the leading causes of death worldwide. The rise of multi-drug resistance and the generation of Cancer Stem Cells (CSCs) is seriously threatening the success of current chemotherapy and good prognosis. Aldehyde Dehydrogenase family (ALDH, EC: 1.2.1.3) has recently attracted the scientific community as a new valuable pharmacological target. ALDHs are detoxifying enzymes involved in the conversion of reactive aldehydes into the corresponding carboxylic acids. The 1A1 isoform (ALDH1A1) has been identified as a CSC biomarker and is associated with chemoresistance mechanisms and aggressive cancer phenotypes. Moreover, ALDH1A1 overexpression was found in several diseases like obesity, diabetes, and solid tumors, thus its inhibition may provide a potential therapeutic approach. In the last years, derivatives of the natural Isatin were reported to strongly inhibit ALDH enzymes. Interestingly, Isatin scaffold seems to share common chemical features with dihydroBenzoImidazoTriazineDione (BITD), a core previously investigated by us as a perspective inhibitor of aldose reductase. Therefore, we repositioned BITD nucleus and, based on the retrieved knowledge of ALDH enzymes, we designed new BITDs in order to allow the interaction with the target 1A1 enzyme. Through a microwave-assisted 3-step approach, a focused library of 2,10-disubstituted BITDs was synthesized. From enzymatic assays, one compound emerged as a selective inhibitor of ALDH1A1 over the 1A2 and 1A3 isoforms. Through in silico studies, we rationalized the results, providing insights into the chemical features required for selectivity and the specific interaction networks for further optimization.

21 randomly selected drugs and excipients of different molecular structures (nipagin M, nipagin P, theophyline, caffeine, triclosan, phenylbutasone, vitamin k3, indomethacin, benzophenone-4, lormetazepam, elenium, naproxen, ibuprofen, bromazepam, aspirin, medazepam, spironolactone, cortisone acetate, olanzapine, chloramfenicol, sumatriptan) were subjected to HPLC chromatography on two different stationary phases: RP-18 and RP-18Ar using the 50:50 (v/v) binary mixture of pH 7.4 phosphate-buffered saline – acetonitrile as a mobile phase. Skin permeability coefficients log K_p of studied compounds were predicted in silico using Pott’s model. The relationships between the chromatographic retention factors log k of compounds listed above obtained for both stationary phases and their predicted skin permeability were investigated. It was concluded that C-18 HPLC retention parameters are not suitable as sole predictors of skin permeability. Multivariate linear (MVL) models of log K_p obtained for the studied group of compounds account for up to 73% of total variability. Calculated and chromatographic descriptors in MVL models were selected in the following order: TPSA (topological polar surface area); #FRB (total count of freely rotatable bonds); log k_RP-18Ar (chromatographic retention factor); F_Csp3 (fraction of sp³ carbon atoms). Chromatographic retention factors on the RP-18Ar stationary phase are more useful than those obtained on RP-18.

Aptamers are small oligonucleotides that specifically recognize a molecular target with high affinity and specificity. Based on their versatility and physicochemical properties, several techniques were developed to exploit the advantages of aptamers as probes for molecular imaging. In our previous work, a DNA aptamer which exhibits specific binding for PTK7 receptor, was used as a molecular imaging probe. This aptamer was modified at 5'-position with several chelator agents and radiolabeled with technetium-99m or gallium-67. An Alexa647 derivative was also used as near infrared dye. All probes were physicochemical and biologically evaluated in BALB/c mice bearing lymphoma-tumor. In order to increase the specificity, the RP-HPLC purification procedure of probes was very strict. The chemical modifications were confirmed by mass spectrometry and RP-HPLC-gamma detection. Confocal microscopy and flow cytometry were performed in several tumor cells with the fluorescent probe. In vivo images were obtained in mice using X-ray, gamma and optical imaging strategies. After 24 h of injection, the probes were retained in the tumor and ratios tumor/non-target organ with values over 20 were obtained. In addition, in vivo specificity was evaluated in competition assays. The retention over time of the probe in the tumor and its quick excretion support the utility of labeled aptamers as molecular probes for diverse image strategies. Currently, a multidisciplinary pipeline is being developed to design and create bispecific aptamers against epitopes of interest, combining theoretical strategies together with experimental approaches using cell lines and ex vivo tumor samples, to guide the structural fine-tuning of selected aptamers.