Chalcones possessing potential anti-Alzheimer’s activity were synthesised in our lab using the Claisen Schmidt reaction. FDS protocols in accordance with ICH guidelines were applied to three thiophene chalcones TC1, TC2, and TC3. The method was developed using Thermo Scientific C18 column (250 x 4.6 mm, 5µm) as stationary phase and sodium acetate buffer (pH 3.0): acetonitrile (40:60, v/v; 40:60, v/v; 25:75, v/v respectively) as the mobile phase at 1 ml/min flow rate and 280 nm as detection wavelength. The developed method was successful in resolving TC1, TC2 and TC3 from its degradation products. TC1, TC2 and TC3 were eluted at a retention time of 10.5min, 27.4 min and 10.2min respectively.

HPLC method was developed and validated for the individual untreated molecules and was found to be specific, selective, precise, reproducible, robust and linear in the range of about 5-15 ppm of the working standard concentration. The chalcones were stable under thermal and thermal-humidity stress, but degraded to different extents under acid-and base-catalyzed hydrolysis, oxidative stress and photolytic conditions, as seen by HPLC analysis. The degradation of TC1 was studied by LC-MS and predictions of the mechanism of degradation were attempted.

During the last decade, superparamagnetic iron oxide nanoparticles (SPIONs) have attracted the scientific community’s interest due to the multitude of applications in many fields of biomedicine namely as contrast media in diagnosis or as carriers for targeted drug delivery. We investigated the immunotoxicity of hydrophilic and surface functionalized SPIONs in vitro against THP-1-derived macrophages. Superhydrophilic ultra-small SPIONs (diameter ~4 nm) were produced by "trimming" the surface coating of the as-prepared nanoparticles. Cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Flow cytometry was employed to study the effect of SPIONs on the redox stage of the cells through the detection of reactive oxygen species (ROS) generation using 2',7'-dichlorofluorescin-diacetate (DCF-DA), the induction of apoptosis using Annexin V-FITC/Propidium Iodide (PI) staining and the estimation of the percentages of cell population in different phases of the cell cycle (PI staining). A dose-dependent reduction in cell viability was recorded after treatment for 24 hours, which was more evident at doses higher than 5 μg/ml. The cytotoxicity of SPIONs was accompanied by a steep increase in ROS production and apoptotic cell population. Cell cycle analysis revealed that SPIONS (5 μg/ml) arrested THP-1-derived macrophages at G0/G1 phase. Our results showed that the ultra-small SPIONs induced immunotoxic effects causing the death of THP-1-derived macrophages. Nonetheless, this novel synthetic approach allows proceeding to further modifications to produce improved SPIONs that can deliver their beneficial promises to the biomedical field.

Steroidal compounds that contain a heterocyclic ring or heteroatom in their structure usually possess good anticancer activity. The main goal of modern medicinal chemistry is to find new potent agonists or antagonists of naturally occurring hormones for the treatment of hormone-dependent cancers such as the above-mentioned steroid derivatives. Here we reported a two-step synthesis of a new 17β-acetoxy-17α-(pyridin-2-yl) derivative of estra-1,3,5(10)-triene. Configuration at the C17 position was determined using the 2D NMR spectra. Furthermore, in silico ADME properties were determined for the synthesized compound. The physicochemical properties were calculated by the SwissADME web tool and compared with five different sets of criteria: Lipinski, Veber, Egan, Ghose, and Muegge. The toxicity of the synthesized compound was predicted and analyzed using a virtual lab ProTox II.

The programmed cell death ligand (PD-L1) is expressed on a number of different tumor entities and inhibits the immune response through binding to PD-1 on T-cells. Immune checkpoint inhibitors (ICI) prevent this blockade and thus can reactivate an immune response. However, only about 30% of the patients respond to an ICI monotherapy. Therefore, clinicians are in need for a non-invasive PET/SPECT radioligand for patient stratification and therapy monitoring.

Based on the structures of non-peptidic PD-L1 inhibitors, six different radiotracers were synthesized and radiolabelled with [⁶⁴Cu]Cu²⁺ (HZDR, 30 MeV TR-FLEX cyclotron). Binding affinities were determined on PC3 cells stably overexpressing hPD-L1. For in vivo studies, qualitative PET/CT imaging experiments (nanoSCAN PET/CT, Mediso) were performed in NMRI-FoxN1-nude mice bearing PC3-hPD-L1 and mock xenograted tumors.

Two PD-L1 inhibitors were modified with strongly water-soluble acid groups, hydrophilic linker units and a NODAGA-chelator resulting in six different radioligands. The log(D) values of the copper-64 labelled radiotracers were between –3.17 and –4.15 and binding affinities ranged between 80.5 and 533 nM. Depending on the number and the pattern of sulfonate and phosphonate groups, in vivo experiments showed drastically different pharmacokinetic profiles. The radiotracer with one sulfonate and phosphonate group and the most hydrophobic linker exhibited a short circulation time, renal clearance, good tumor uptake (SUV_max = 3.5) and a distinct contrast between the hPD-L1 and the mock tumor.

In conclusion one PD-L1 radiotracer showed a promising pharmacokinetic profile, which is currently further modified to improve the binding affinity and tumor uptake.

Due to their unique physicochemical properties, the use of graphene-based nanomaterials in biomedical applications has attracted great interest over the last decade. Nonetheless, evaluation of the biocompatibility of a nanomaterial is a crucial prerequisite before its use in biomedical applications. Recently, green exfoliation methods have emerged as more economical and sustainable approaches for producing graphene from graphite. The aim of this study was to evaluate the toxicity and biocompatibility of graphene that has been synthesized either with chemical or green procedures. In vitro assays were performed against THP-1-derived macrophages. Cytotoxicity was assessed with MTT assay, and examination of the redox stage of cells, evaluation of apoptosis and cell cycle analysis, were performed using Flow cytometry. Chemical graphene’s exfoliation requires the use of toxic solvent DMF, and thus its toxicity assessment was limited to low doses (≤20 μg/mL). At these doses both materials weren’t cytotoxic, however green graphene’s lack of chemicals made it biocompatible even at 10x higher doses. Flow cytometry showed that none of the nanomaterials generated intracellular ROS, induced apoptotic death or cell cycle arrest. While both materials seem to be safe at low doses, green exfoliated- graphene could be used at higher doses. Moreover, it’s sustainable and economical way of production make it an ideal candidate for biomedical applications (i.e., biosensing, drug delivery etc.). Further research on the activation of molecular pathways of inflammation by green graphene could prove its value for use in such applications.

1,2,3-Triazole ring has remarkable importance in medicinal chemistry due to its unique biological properties such as metabolic stability and ability to form hydrogen bonds. Several biological activities had been reported for this structural nucleus, while paracetamol (acetaminophen, N-(4-hydroxyphenyl)acetamide) is one of the most popular and widely used drugs for the treatment of pain and fever. Applying a molecular hybridization strategy, numerous 1,2,3-triazole-based compounds have been designed, prepared, and studied for pharmacological applications in multiple laboratories around the world. Considering this context, we used expired acetaminophen pills as starting material for generating new series of functionalized paracetamol-1,2,3-triazole hybrids. Their synthesis consists of Cu(PPh₃)₃Br-catalyzed 1,3-dipolar cycloaddition reaction of O-propargyl-acetaminophen and several azides prepared from commercially available anilines, following the protocol reported by Filimonov et al. Performing click chemistry and considering green chemistry principles, interesting paracetamol-1,2,3-triazole derivatives were easily prepared in 64-93 % yields. Obtained hybrids were subjected to In Silico analysis (Molinspiration, OSIRIS and DRUDIT), evaluating some physicochemical properties and toxicity risks. According to the predicted biological properties, most of the prepared hybrid molecules exhibit adequate parameters as potential pharmacological agents, presenting high inhibitory activity, low risks of toxicity, and good affinity for various biological targets. This work highlights the recycling of expired drugs and the accessibility to new paracetamol-based compounds under green mild reaction conditions (H₂O/tert-BuOH mixture, rt) and low catalytic loads (1 mol% Cu(PPh₃)₃Br).

Adansonia digitata L. (Malvaceae, Baobab) is a medicinal tree with antimicrobial, antiviral, anti-inflammatory, and antioxidant properties. The leaves, fruit pulp, stem bark, and roots have been extensively studied. The aim of this study was to evaluate the glucose-lowering and in vitro antidiabetic potentials of the aqueous extract of A. digitata seed. The aqueous extract of A. digitata seed was prepared by dissolving 50 g of powder seed in 500 mL of distilled water for 24 hours, filtered using Whatman filter paper, and concentrated using a rotary evaporator at 40^oC. Following an oral administration of glucose (2 g/kg body weight), distilled water, metformin (14.2 mg/kg body weight), and A. digitata seed extracts at 500 and 1000 mg/kg body weight respectively. Results show that the untreated mice had an average of 11.09% increase in plasma glucose concentration, while metformin, aqueous seed extract of A. digitata had an average of 17.05%, 0.99%, and 19.21% decrease in plasma glucose concentration respectively. The aqueous seed extract of A. digitata inhibited α amylase in a concentration-dependent manner with an IC₅₀ of 24.27±2.14 mg/mL compared with acarbose with IC₅₀ of 22.61±1.05 mg/mL. However, the α-glucosidase inhibitory activities of the extract (IC₅₀ 34.37±1.67 mg/mL) were significantly lower compared to acarbose (IC₅₀ 53.46±2.06). The study concludes that aqueous seed extract of A. digitata possesses glucose-lowering properties, in vitro α-amylase and α-glucosidase inhibitory potentials.

Nicardipine (NC) is an antihypertensive drug indicated for treatment of high blood pressure and angina. It belongs to BCS class-II having poor solubility and low oral bioavailability. The present work was aimed to develop pyromellitic dianhydride (PMDA) cross-linked β-cyclodextrin (βCD) nanosponges (NS) for improved solubility and drug release. The βCDNS were prepared by solvent evaporation method in 1:2, 1:4, 1:6 w/w ratio of β-CD: PMDA. The prepared drug loaded β-CDNS were subjected to characterization studies such as DSC, FESEM, FTIR, PXRD and particle size. Characterisation studies confirmed the formation of nanosponges and entrapment of drug molecule into it. The βCDNS prepared in 1:4 w/w ratio of βCD: PMDA showed highest increase in solubility and entrapment efficiency with particle size of 411nm and -20.9 mV zeta potential. The molecular docking study revealed formation of stable complexes through interaction of NC and βCD. The Nanosponges were formulated into capsule dosage form by blending the drug-loaded nanosponges with granulated excipients such as talc, aerosol, lactose and starch. The powder blend showed acceptable flow properties. The in vitro dissolution studies of the optimized capsule formulation performed by using USP Type-I apparatus showed considerably higher drug release compared to pure NC. Thus, PMDA cross-linked βCDNS represent a novel approach for solubility enhancement and improved dissolution of selected model drug .

Microtubule-targeted drugs are essential chemotherapeutic agents for various types of cancer. We have previously reported the synthesis of 3-vinyl-β-lactams (2-azetidinones) with potent antiproliferative activity against breast cancer MCF-7 cells ^[1]. As a continuation of our research work on tubulin polymerization inhibitors, we now present the synthesis and biochemical evaluation of a series of novel 3-isopropenyl-β-lactams (2-azetidinones) that are structurally related to the colchicine binding site tubulin inhibitor and vascular targeting agent, Combretastatin A-4. The 3-isopropenyl-β-lactams in this series contain 3,4,5-trimethoxyphenyl ring A, (required for CA-4), together with selected ring B substituents ^[2]. These compounds showed potent activity against breast cancer in MCF-7 and MDA-MB-231 cells and are minimally toxic to non-tumorigenic HEK-293T cells. Moreover, the compounds significantly arrested cell division during the G2/M phase and induced apoptosis in the MCF-7 cell line. Immunofluorescence studies in MCF-7 cells showed that the 3-isopropenyl-β-lactam caused mitotic catastrophe by targeting tubulin and inhibited tubulin polymerization. In conclusion, the 3-isopropenyl-2-azetidinones could be promising lead compounds for the development of anti-breast cancer drugs that target tubulin in future clinical trials.

^{Chromatographic retention factors (log k}_KERATIN ^{) of 33 molecules were obtained on an immobilized keratin stationary phase by Turowski and Kaliszan (J. Pharm. Biomed. Anal. 15, 1997, 1325-1333). Their objective was to develop a novel stationary phase that could be used to investigate the skin permeability coefficient of solutes (log K}_p^{) in vitro. However, log k}_KERATIN ^{is not a sufficiently good predictor of skin permeability coefficient to be used as a sole descriptor in log K}_p ^{models. Turowski and Kaliszan reported that this descriptor can be used combined with the chromatographic retention factor obtained by Immobilized Artificial Membrane chromatography (log k}_IAM^{) and the results of log K}_p ^{predictions using multiple linear regression (MLR) models are moderately satisfying.}

^{In this study the values of log k}_KERATIN ^{obtained by Turowski and Kaliszan were correlated with a set of descriptors calculated using SwissADME software. It was discovered that log k}_KERATIN ^{encodes primarily lipophilicity, solubility and molecular size descriptos, which are important factors governing the ability of compounds to cross the skin barrier. On the other hand, log k}_KERATIN ^{does not correlate with polar surface area (PSA) and the molecule's ability to form hydrogen bonds - which are important properties in the context of solutes' skin permeability.}

^{It was concluded that log k}_KERATIN ^{could be used as a descriptor in MLR models of log k}_p ^{in combination with other parameters , such as PSA or H-bond descriptors.}