Malignant melanoma poses a significant global health burden. It is the most aggressive and lethal form of skin cancer, attributed to various risk factors such as UV radiation exposure, genetic modifications, chemical carcinogens, immunosuppression, and fair complexion. Photodynamic therapy is a promising minimally invasive treatment that uses light to activate a photosensitizer, resulting in the formation of reactive oxygen species, which ultimately promote cell death. When selecting photosensitizers for melanoma photodynamic therapy, the presence of melanin should be considered. Melanin absorbs visible radiation similar to most photosensitizers and has antioxidant properties, which undermines the reactive species generated in photodynamic therapy processes. These characteristics have led to further research for new photosensitizing platforms to ensure better treatment results. The development of photosensitizers has advanced with the use of nanotechnology, which plays a crucial role in enhancing solubility, optical absorption, and tumour targeting. This paper reviews the current approaches (that use the synergistic effect of different photosensitizers, nanocarriers, chemotherapeutic agents) in the photodynamic therapy of melanoma.

Recent research papers have confirmed the prevalence of microorganisms resistant to numerous antimicrobial agents, leading to spreading infections, extended hospitalizations, and increased mortality rates. The amplifying factors stimulate the need to discover new molecules able to cut off the developing resistance of pathogens against medicines. The current study presents a molecular docking procedure applied on 15 new pyridine–thiourea derivatives in order to test their activities against S. aureus and E. coli. The protein crystal structures were obtained from the Protein Data Bank (PDB). Processes such as geometry optimization, molecular properties (log P, polarizability, E HOMO, E LUMO, area and volume of the molecules, and ovality), drug-likeness, pharmacokinetic and pharmacogenomic profiles, and molecular docking studies are discussed in the present research. The approach involved the determination of the molecular properties for each chemical structure by using the Spartan 14 software, followed by the evaluation of their binding affinity through a specific docking score with the aid of the CLC Drug Discovery Workbench. Each studied compound established hydrogen bonds with the selected receptors, leading to suitable docking scores and increasing the chances of the compound being considered for further investigation.

Novel phthalimide derivatives, namely N-(1,3-dioxoisoindolin-2-yl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide (1a) and N-(1,3-dioxoisoindolin-2-yl)thiophene-2-carboxamide (1b), and hexahydrophthalimide derivative N-(1,3-dioxohexahydro-1H-isoindol-2(3H)-yl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide (2), have been synthesized. The phthalimide derivatives were synthesized from phthalic anhydride and 2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide or thiophene-2-carbohydrazide, and the hexahydrophthalimide derivative has been synthesized from hexahydrophthalic anhydride and 2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide. The chemical structures of the compounds are elucidated by Nuclear Magnetic Resonance (NMR) and Infrared (IR) spectra. The new in vitro antioxidant activities of the obtained substances were evaluated using the DPPH method. All tested compounds showed antioxidative activity, the most active compound being 1b. Bioinformatics tools were used for the prediction of pharmacokinetics and pharmacodynamics profiles. Our results showedthat all compounds have a suitable intestinal absorption rate, good BBB and CNS permeabilities and have as molecular targets MAO B, COX-2 and NF-KB, important for antioxidant activities.

The chemical compounds from extracts of three Ranunculaceae species, Aconitum toxicum Rchb., Anemone nemorosa L. and Helleborus odorus Waldst. & Kit. ex Willd., respectively, were isolated using the HPLC purification technique and analyzed from a bioinformatics point of view. The classes of compounds identified based on the proportion in the rhizomes/leaves/flowers used for microwave-assisted extraction and ultrasound-assisted extraction were alkaloids and phenols. Here, the quantifying of pharmacokinetics, pharmacogenomics and pharmacodynamics helps us to identify the actual biologically active compounds. Our results showed that (i) pharmacokinetically, the compounds show good absorption at the intestinal level and high permeability at the level of the central nervous system for alkaloids; (ii) regarding pharmacogenomics, alkaloids can influence tumor sensitivity and the effectiveness of some treatments; (iii) and pharmacodynamically, the compounds of these Ranunculaceae species bind to carbonic anhydrase and aldose reductase. The results obtained showed a high affinity of the compounds in the binding solution at the level of carbonic anhydrases. Carbonic anhydrase inhibitors extracted from natural sources can represent the path to new drugs useful both in the treatment of glaucoma, but also of some renal, neurological and even neoplastic diseases. The identification of natural compounds with the role of inhibitors can have a role in different types of pathologies, both associated with studied and known receptors such as carbonic anhydrase and aldose reductase, as well as new pathologies not yet addressed.

Background: During the current SARS-CoV-2 pandemic, the identification of effective antiviral drugs is crucial. Unfortunately, no specific treatment or vaccine is available to date. Objective: Here, we aimed to predict the interactions between SARS-CoV-2 proteins and protein targets from the human body for some flavone molecules (kaempferol, morin, pectolinarin, myricitrin, and herbacetin) in comparison to synthetic compounds (hydroxychloroquine, remdesivir, ribavirin, ritonavir, AMD-070, favipiravir). Methods: Using MOE software and advanced bioinformatics and cheminformatics portals, we conducted an extensive analysis based on various structural and functional features of compounds, such as their amphiphilic field, flexibility, and steric features. The structural similarity analysis of natural and synthetic compounds was performed using Tanimoto coefficients. The interactions of some compounds with SARS-CoV-2 3CLprotease or RNA-dependent RNA polymerase were described using 2D protein-ligand interaction diagrams based on known crystal structures. The potential targets of considered compounds were identified using the SwissTargetPrediction web tool. Results: Our results showed that remdesivir, pectolinarin, and ritonavir present a strong structural similarity which may be correlated to their similar biological activity. As common molecular targets of compounds in the human body, ritonavir, kaempferol, morin, and herbacetin can activate multidrug resistance-associated proteins, while remdesivir, ribavirin, and pectolinarin appear as ligands for adenosine receptors. Conclusion: Our evaluation recommends remdesivir, pectolinarin, and ritonavir as promising anti-SARS-CoV-2 agents.