Osteosarcoma (OS) is the most common childhood bone sarcoma, Current therapies include preoperative neoadjuvant therapy, tumor resection, and postoperative adjuvant therapy. In cases of recurrent disease, this regimen is limited by poor overall survival rates, therefore, novel therapeutic agents are required. Recently, flavonoids have been reported to inhibit OS development, which suggests the therapeutic benefit of this type of molecules in OS.

The aim of this study was to evaluate the cytotoxicity of 3,7,3’,4’-tetrahydroxyflavone compounds in OS. MG-63, Saos-2, HOS and 143B human OS cell lines were incubated with six flavonoids, at final concentrations of 0 – 160 µM, for 48h. After this period, the inhibition of OS cell proliferation and growth was evaluated by WST-8 and sulforhodamine B spectrophotometric assays. The most active inhibitors possessed triple hydroxylation at the B-ring, at C-3’, C-4’, and C-5’. In contrast, hydroxylation at C-5 of the A-ring resulted in poorer inhibition of cell proliferation and growth. These results reveal new substitutions to improve the cytotoxic activity of flavonoids, and postulate further investigation of the cellular effects of these compounds in human OS.

Diarylpentanoids comprise a class of natural products and their synthetic analogues well known for their antitumor activity. Recently, the diarylpentanoid BP-M345 has been identified as a potent in vitro growth inhibitor of human colon cancer HCT116 cells expressing wt p53, with a GI₅₀ value of 0.17 µM, showing low toxicity in non-tumor HFF-1 cells. However, it was observed that BP-M345 has no effect on the inhibition of the p53-MDM2 interaction. Further insights into the mechanisms through which this compound could exert growth inhibitor activity were pursued. Considering that BP-M345 possesses 3,4,5-trimethoxyphenyl groups that have been much highlighted as playing crucial role in the interaction with tubulin in MTAs, it was hypothesized that this diarylpentanoid could also act as a antimitotic agent. Its antiproliferative activity was evaluated in human tumor cell line by sulforhodamine B assay. BP-M345 promoted a prolonged SAC-dependent mitotic arrest by interfering with mitotic spindle assembly, followed by massive apoptosis. The overall results indicate that the diarylpentanoid BP-M345 exerts its antiproliferative activity by inhibiting mitosis through microtubule perturbation and causing cancer cell death, highlighting its potential as antitumor agent. Additionally, docking poses and residues involved in the binding site of α,β-tubulin were predicted by docking studies.

Systemic fungal infections by filamentous fungi, particularly in the immunocompromised population, represent a serious threat to public health. The increase of resistant strains to classic antifungal drugs, especially azoles, is a global health problem and some infections become almost impossible to treat. Furthermore, the emergence of new multidrug-resistant fungal species, such as Scedosporium spp. and Fusarium spp., as etiological agents, pose a challenge in the treatment. On the other hand, superficial fungal infections by dermatophytes have a high incidence affecting around 20 to 30% of the healthy human population. Therefore, the discovery and development of new antifungal compounds with a broad-spectrum and able to modulating and/or eradicating antifungal resistance have become an essential and urgent strategy. Taking into account that thioxanthones are privileged structures and bioisosteres of xanthones, three thioxanthones were synthesized and, subsequently, their activity as potential agents against filamentous fungi were evaluated. Minimum inhibitory concentration and minimum lethal concentration was tested against clinically relevant species, using the broth microdilution method. The derivatives were synthesized through aromatic nucleophilic substitution reactions, using a chlorinated thioxanthone and a primary amine as building blocks, and showed interesting results against most of the isolates tested, including strains intrinsically resistant or that acquired resistance to fluconazole or other azoles; among the tested compounds, one of the thioxanthone showed more promising activity. These findings highlight the potential value of the thioxanthone derivatives as new models for antifungal agents for the treatment of systemic and superficial fungal infections.

A large number of synthetic cannabinoids are included in new psychoactive substances (NPS) and constitute an open research area in analytical pharmaceutical and toxicology, when methods are needed to unambiguously identify these substances and their metabolites in biological fluids. A full molecular characterization of five synthetic cannabinoid molecules of the URB series was achieved by high resolution mass spectrometry (HRMS) in positive ion electrospray ionization and collisional experiments on the protonated parent ions obtaining characteristic fragmentation patterns. Ultra–high performance liquid chromatography (UHPLC–MS/MS) has also been used, which can help develop methods for screening and confirming synthetic cannabinoids in biological fluids.

The rapid spread of fatal diseases forces us to reconsider our position as researchers in the field of drug development assisted by computer. Alternatively, new drugs are constantly being developed from natural compounds using computer-aided methods. The virtual screening is carried out in accordance with protocols established by accredited organizations and is based on the structure of ligands or the structure of target proteins. The formation of a data base based on phytotherapy is the best option because Morocco is known for its wealth of plants and their traditional uses in medicine, which encourages us to better utilize our cultural heritage and the diversity of our country nature in the therapeutic field. The combination of these fields of CADD and Phytotherapy can yield positive results in terms of the development of molecules with the goal of using them as drugs capable of inhibiting a pathological protein. In the present study, deep research was done to collect a set of phytoconstituents extracted from Moroccan plants to evaluate their ability to limit the proliferation of SARS-CoV-2. Molecular docking was done in the active site of 6lu7 and 6m0j proteins to assess their binding affinity. The structural stability of the target protein was validated by redocking. The compounds with good values of binding affinity were further subjected to Lipinski’s rule of five, chemical absorption and toxicity analysis. The results revealed that only 2 compounds present good binding affinity towards target proteins and able to be oral available medication against SARS-CoV-2.

The spectrums of biological activities of aurone and its derivatives have strongly attracted biologists and chemists these days. The therapeutic profile of aurone is leading to an emerging paradigm and tremendous growth in the contemporary drug discovery regime, and also the existing data on the bioactivity of natural and synthetic aurones is very promising. The exploration of hybrid molecules for targeting various diseases represents a highly promising approach that has showcased significant momentum worldwide in the last two decades. Pyrazole, chloroquinoline, coumarin, and chromone nuclei are well known for their potency in various biological activities and are part of many existing drugs. The hybrids of these heterocycles are the center of interest for chemists for the latest drug discovery. Therefore we have synthesized and characterized some novel hybrid aurones bearing pyrazole or quinolone nucleus along with benzofuran in a single chemical unit. These hybrid aurones have been evaluated as potent cytotoxic and anti-biofilm agents.

Basil (Ocimum basilicum L.) has a long traditional use as spice in both folk and conventional medicine. Basil extracts (BEs) as well as essential oil (EO) represents a rich source of phytochemicals, many of which possess diverse biological activities. The objectives of this study were to assess antioxidant and antibacterial activities of BEs and EO, obtained from plants cultivated in Republic of Serbia. EO was isolated by hydrodistillation, while BEs were obtained by Soxhlet extraction and ultrasound-assisted maceration, using 70% and 96% ethanol. In prepared BEs total phenolic (TPC) and total flavonoid content (TFC) were determined spectrophotometrically. Antioxidant activity was evaluated by DPPH and FRAP assays. A higher TPC was obtained using 70% ethanol, while 96% ethanol proved to be more effective for the extraction of flavonoids. In both antioxidant assays, BEs showed remarkable antioxidant properties compared to EO. Also, regardless the extraction method and assay applied, the 70% ethanol extracts proved to be more potent than 96% ethanol ones. Both antioxidant assays strongly correlated with TPC than with TFC. For antibacterial activity assay, minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) were obtained by the microdilution method. Tested Gram-negative bacteria (E. coli and S. Typhimurium) were more resistant than Gram-positive (S. aureus and L. monocytogenes). Opposite to results of antioxidant activity, EO expressed superior antibacterial activity. Based on the obtained results, it can be concluded that basil represents powerful source of biologically active components which can express strong antioxidant and antibacterial activity.

Alzheimer's disease (AD) is the age–related most common cause of dementia among elderly people, and a severe neurodegenerative disorder characterized by progressive memory and cognition losses, leading to disability and inevitably to death, considered as an urgent public health problem. It is the third leading cause of death after cancer and heart diseases. According to an update in 2020 of the estimates given in the World Alzheimer Report 2015, there are over 50 million people worldwide living with dementia in 2020. This number will almost double every 20 years, reaching 152 million in 2050. AChE inhibitors are the main stay drugs for early disease stages.

In this work we report on the development of a synthetic route to yield open chain sugar amides from commercially available carbohydrates. The synthetic pathway starts with diacetone glucose (DAG), which is converted into perbenzyl d-glucono-1,4-lactone in six steps. Reaction with aromatic or aliphatic amines in dichloromethane under reflux (0.5 h to 2 h) afforded the corresponding amides in high yield (80 – 95%) (Scheme 1). Bis(amidation) of a diamine was also accessed by this procedure in 3 h but reaction product was isolated in very low yield (13%). Docking studies and evaluation of acetylcholinesterase inhibition were carried out and the results will be disclosed.

Breast cancer is a worldwide health problem, being one of the most prevalent types of tumors in the female population. Despite the availability of many therapies, including doxorubicin, novel chemotherapeutic approaches are being studied for this disease, focusing on triple-negative breast cancer cells. Cathepsin L is a cysteine protease highly expressed in many tumors, where novel dipeptidyl nitrile inhibitors have been designed and studied over time in our research group. Here, an approach involving the combination therapy of twelve novel cathepsin L inhibitors and doxorubicin was assayed against the triple-negative human breast cancer cell line MDA-MB-231. The cells were cultivated using DMEM medium supplemented with 10% FBS. They were added to 96-plates at a concentration of 1.0x10^5 cells/well (100 microL/well). After 24 h incubation, the medium was removed to add 10 micromolar cathepsin L inhibitors and a range of doxorubicin concentrations (1.0-1 nanomolar). The system was incubated for 72 h, being subject to MTT assay. The Bliss test was used to evaluate the concentration-dependent assay of these chemicals, which led to synergism for many chemicals. The best combination led to almost 8-times higher potency improvement than doxorubicin alone. The SAR was described for the set of dipeptidyl nitriles. It is not yet known how these chemicals could act in combination, and this is the current subject of our efforts to exploit biological mechanisms.

Catalytically active carbonic anhydrases (CAs) control the rate of the reversible hydration of CO₂ to HCO₃^- and H⁺¹. In particular, the isoform VII (CA VII) appears to be involved in seizure generation and represents a promising molecular target for the design of anticonvulsant drugs. By means of an experimentally validated docking protocol, a series of N,N'-disubstituted sulfamides derivatives were selected as potential new CA VII inhibitors. They present the general structure R-NH-SO₂-NH-(CH₂)₃-COOCH₃, since they share the gamma-aminobutyl (GABA) methyl ester scaffold.
The synthesis starts with the preparation of catechol sulfate using sulfuryl chloride and catechol. Then, this cyclic sulfate reacts with the amino group of the GABA methyl ester to give the corresponding sulfamate. Finally, the sulfamide is generated by the substitution reaction between catechol and the amine with the second substituent (R), releasing the catechol in equimolar quantities.
The synthesized compounds will be evaluated in vitro for their activity on CA VII and then the most promising candidates will be tested in vivo in acute mouse models of seizures.