Azulene and Its Derivatives as Potential Compounds in the Therapy of Dermatological and Anticancer Diseases: New Perspectives against the Backdrop of Current Research.

The scientific article focuses on the role of azulene and its derivatives in the therapy of dermatological diseases, presenting the latest laboratory and clinical research as well as prospects for further studies. In a synthetic literature review, various databases such as PubMed, Scopus, Web of Science, and the Database of Polish Scientific Journals were queried to select relevant articles concerning azulene. The conclusions drawn from the thematic analysis of the studies emphasize the multifaceted pharmacological actions of azulene and its derivatives including their anti-inflammatory properties, potential anticancer effects, photoprotective abilities, alleviation of itching, management of atopic dermatitis, and treatment of erectile dysfunction. However, there are certain limitations associated with the application of unmodified azulene on the skin, particularly related to photodecomposition and the generation of reactive oxygen species under UV radiation. These effects, in turn, necessitate further research on the safety of azulene and azulene-derived substances, especially regarding their long-term use and potential application in phototherapy. The authors of this work emphasize the necessity of conducting further preclinical and clinical studies to fully understand the mechanisms of action. Incorporating azulene and its derivatives into the therapy of dermatological disorders may represent an innovative approach, thereby opening new treatment avenues for patients.

Efficacy of photodynamic therapy using ALAHCl in gel with a lipid nanoemulsion and MALHCl in cream in superficial basal cell carcinoma.

INTRODUCTION AND OBJECTIVE: Photodynamic therapy (PDT) is a therapeutic option for low-risk basal cell carcinoma (BCC). The aim of the study was to assess the efficacy of topical PDT in the treatment of superficial BCC (sBCC) using two different photosensitizers: aminolevulinic acid hydrochloride (ALA-HCl) in a gel formulation with a lipid nanoemulsion (ALA-HCl in gel) and ALA methyl ester hydrochloride (MAL-HCl) in a cream formulation (MAL-HCl in cream). MATERIAL AND METHODS: 21 patients were treated twice with a one week interval between treatments. The formulations were applied onto lesions: 10 patients were treated with MAL-HCl in cream, and 11 with ALA-HCl in gel. After three hours of incubation and removing the preparations, fluorescence was assessed. The skin areas were then irradiated with red light 630 ± 5 nm. RESULTS: At the follow-up visit 12 weeks after the second treatment, complete clinical remission was found in 82% after ALA-HCl in gel and in 80% after MAL-HCl in cream. An excellent cosmetic result was found in 96% of patients after MALHCl in cream and in 100% after ALA-HCl in gel. Faster skin healing and less post-inflammatory hyperpigmentation during follow-up visits was observed after treatment with ALA-HCl in gel. CONCLUSIONS: Both formulations - ALA-HCl in gel and MAL-HCl in cream - were highly effective photosensitisers for PDT. The advantage of ALA-HCl in a gel formulation with a lipid nanoemulsion was faster skin healing, resulting in better cosmetic results.

Structure-activity relationship and cytotoxicity of the new thiosemicarbazide derivatives and their Cu(II) complexes against prostate and melanoma cancer cells.

In this study, eighteen new ligands (B1-B18) containing a thiosemicarbazide core were synthesized and characterized in terms of physicochemical properties, molecular docking and in vitro biological activity. The structures of eleven ligands were investigated using X-Ray diffraction and Hirschfeld Surface analysis. To study the structure-activity relationship, the organic ligands contained pyridin-2-ylmethyl, pyridin-3-ylmethyl or pyridin-4-ylmethyl moieties and various substituents. Their pharmakokinetic profiles and molecular docking results suggest high potential as new drug candidates. The complexing ability of the selected organic ligands was also evaluated, yielding five new Cu(II) complexes (Cu(B1)Cl2, Cu(B4)Cl2, Cu(B10)Cl2, Cu(B17)Cl2, Cu(B18)Cl2). The obtained results suggest the formation of the polymeric structures. All organic ligands and Cu(II) complexes were tested for anticancer activity against prostate and melanoma cancer cells (PC-3, DU-145, LNCaP, A375, G-361, SK-MEL-28) and normal fibroblasts (BJ), as well as antimicrobial activity against six selected bateria strains. Among B1-B18 compounds, B3, B5, B9, B10, B12 and B14 exhibited cytotoxic activity. The studied Cu(II) complexes were in general more active, with Cu(B1)Cl2 exhibiting antincancer activity agains all three prostate cancer cells and Cu(B10)Cl2 reaching the IC50 value equal to 88 µM against G-361 melanoma cells. Several compounds also exhibited antimicrobial activity against gram-positive and gram-negative bacteria. It was found that the type of specific substituents, especially the presence of -chloro and -dichloro substituents had a greated impact on the cytotoxicity than the position of the nitrogen atom in the pyridylacetyl moiety.

N-Substituted 2-(Benzenosulfonyl)-1-Carbotioamide Derivatives Exert Antimicrobial and Cytotoxic Effects via Aldehyde Dehydrogenase Pathway: Synthesis, In Silico and In Vitro Studies.

A series of N-Substituted 2-(benzenosulfonyl)-1-carbotioamide derivatives (WZ1-WZ4) were synthesized and characterized using spectral methods. A comprehensive activity study was performed for each compound. All compounds were tested for antibacterial activity. Moreover, in silico studies were carried out to determine the anticancer potential of the designed WZ1-WZ4 ligands. Based on molecular docking, aldehyde dehydrogenase was selected as a molecular target. The obtained data were compared with experimental data in vitro tests. Novel hybrids of the thiosemicarbazide scaffold and sulfonyl groups may have promising anticancer activity via the aldehyde dehydrogenase pathway. The best candidate for further studies appears to be WZ2, due to its superior selectivity in comparison to the other tested compounds.

Polymer microspheres modified with pyrazole derivatives as potential agents in anticancer therapy - Preliminary studies.

The methods of fighting cancer are far from ideal, therefore it is necessary to search for innovative and effective drugs. In our work, we present pyrazole derivatives and their modifications with polymer microspheres as potential anticancer agents. Molecular and crystal structures of pyrazole derivatives were determined an X-ray analysis and characterized by theoretical calculations. Modifications of cross-linked polymer microspheres with pyrazole derivatives were made on the basis of divinylbenzene and glycidyl methacrylate. The in vitro antiproliferative activity of the pyrazole derivatives and their modified microspheres was assessed against a normal cell line, namely monkey epithelial renal cells (GMK) and cancer cell lines, such as human hepatocellular carcinoma cell line (HepG2), human breast adenocarcinoma cell line (MCF-7) as well as human lung adenocarcinoma cell line (A549), using the MTT assay. All the tested pyrazole derivatives and the polymer microspheres modified by them showed antiproliferative activity in vitro. Two of the modified substances showed the greatest ability to inhibit divisions of all cancer cells. In order to determine a potential target, molecular docking was performed. In silico studies carried out with the use of the human EphB1 receptor revealed that the analyzed compounds bound to the EphB1 binding site, and the compounds with the highest antiproliferative activity showed a better fit to the active site.

Topical Photodynamic Therapy with Different Forms of 5-Aminolevulinic Acid in the Treatment of Actinic Keratosis.

Photodynamic therapy (PDT) is safe and effective in the treatment of patients with actinic keratosis (AK). The aim of the study was to assess the efficacy, tolerability and cosmetic outcome of topical PDT in the treatment of AKs with three forms of photosensitizers: 5-Aminolevulinic acid hydrochloride (ALA-HCl), 5-Aminolevulinate methyl ester hydrochloride (MAL-HCl) and 5-Aminolevulinate phosphate (ALA-P). The formulations were applied onto selected scalp/face areas. Fluorescence was assessed with a FotoFinder Dermoscope 800 attachment. Skin areas were irradiated with Red Beam Pro+, Model APRO (MedLight GmbH, Herford, Germany). Applied treatments were assessed during the PDT as well as 7 days and 12 weeks after its completion. Ninety-four percent of patients rated obtained cosmetic effect excellent. The efficacy of applied PSs did not differ significantly. However, pain intensity during the PDT procedure was significantly lower in the area treated with ALA-P (5.8 on average) in comparison to the areas treated with ALA-HCl or MAL-HCl (7.0 on average on 0-10 scale). Obtained results show that ALA-P may undergo more selective accumulation than ALA-HCl and MAL-HCl. Our promising results suggest that PDT with the use of ALA-P in AK treatment may be an advantageous alternative to the already used ALA-HCl and MAL-HCl.

Novel thiosemicarbazide derivatives with 4-nitrophenyl group as multi-target drugs: α-glucosidase inhibitors with antibacterial and antiproliferative activity.

A series of thiosemicarbazides with 4-nitrophenyl group was obtained in the reaction of carboxylic acid hydrazides with isothiocyanates. All compounds were checked for their antibacterial and antiproliferative activity. Our results have shown that derivatives 6-8 possessed antibacterial activity against S. aureus, S. epidermidis, S. mutans and S. sanguinis, moderate cytotoxicity and good therapeutic safety in vitro. Additionally, compounds 1 and 4 significantly inhibited A549, HepG2 and MCF-7 cell division. Moreover, PASS software indicated that newly obtained compounds are potential α-glucosidase inhibitors. This was confirmed by in vitro studies. To investigate the mode of interaction with the molecular target compounds were docked to glucose binding site of the enzyme and exhibited a similar binding mode as glucose.