Globularia alypum L. (GA) is a Mediterranean plant of the Globulariaceae family which is widely used in traditional Tunisian medicine. The main goal of this study was to evaluate the phytochemical composition, antioxidant, antibacterial, and antibiofilm activities, and the antiproliferative potential of different extracts of this plant. The identification and the quantification of the different constituents of extracts were determined using gas chromatography–mass spectrometry (GC-MS). The antioxidant activities were evaluated using spectrophotometric methods and chemical tests. The antiproliferative study was based on the use of colorectal cancer SW620 cells, including an antibacterial assessment with the microdilution method and analysis of the antibiofilm effects via the crystal violet assay. All extracts presented several components, mainly sesquiterpenes, hydrocarbon, and oxygenated monoterpenes. The results revealed that the maceration extract had the most important antioxidant effect (IC₅₀ = 0.04 and 0.15 mg/mL), followed by the sonication extract (IC₅₀ = 0.18 and 0.28 mg/mL). However, the sonication extract demonstrated significant antiproliferative (IC₅₀ = 20 µg/mL), antibacterial (MIC = 6.25 mg/mLand MBC > 25 mg/mL), and antibiofilm (35.78% at 25 mg/mL) properties against S. aureus. The results achieved confirm the important role of this plant as a source of therapeutic activities.

Nosocomial infections represent one of the biggest health problems nowadays. Acinetobacter baumannii is known as an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived infection. It is known that in recent years, more and more bacteria have become multidrug-resistant (MDR) and, for this reason, the development of new drugs is a priority. However, these products must not affect the human body, and therefore, cytotoxicity studies are mandatory. In this context, antimicrobial peptides with potential antibacterial proprieties could be an alternative. In this research, we describe the synthesis and the bioactivity of dermaseptins and their derivatives against Acinetobacter baumannii. The cytotoxicity of these compounds was investigated on the HEp-2 cell line by MTT cell viability assay. Thereafter, we studied the morphological alterations caused by the action of one of the active peptides on the bacterial membrane using atomic force microscopy (AFM). The cytotoxicity of dermaseptins was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibited antibacterial activity with Minimum Inhibitory Concentrations (MICs) ranging from 3.125 to 12.5 μg/mL and Minimum Bactericidal Concentrations (MBCs) ranging from 6.25 to 25 μg/mL. Microscopic images obtained by AFM revealed morphological changes on the surface of the treated bacteria caused by K₄S4(1-16), as well as significant surface alterations. Overall, these findings demonstrate that dermaseptins might constitute new lead structures for the development of potent antibacterial agents against Acinetobacter baumannii infections.

Zika virus represents the primary cause of infection during pregnancy and can lead to various neurological disorders such as microcephaly and Guillain-Barré syndrome affecting both children and adults. This infection is also associated with urological and nephrological problems. So far, evidence of mosquito-borne Zika virus infection has been reported in a total of 89 countries and territories. However, surveillance efforts primarily concentrate on outbreaks that this virus can cause, yet the measures implemented are typically limited. Currently, there are no specific treatments or vaccines designed for the prevention or treatment of Zika virus infection or its associated disease. The development of effective therapeutic agents presents an urgent need. Importantly, an alternative for advancing the discovery of new molecules could be dermaseptins, a family of antimicrobial peptides known for their potential antiviral properties. In this study, we carried out the synthesis of dermaseptins and their analogs and subsequently assessed the bioactivity tests against Zika virus (ZIKV PF13) of dermaseptins B2 and S4 and their derivatives. The cytotoxicity of these peptides was investigated on HMC3 cell line and HeLa cells by CellTiter-Glo® Luminescent Cell Viability Assay. Thereafter, we evaluated the antiviral activity caused by the action of our dermaseptins on the viral envelope using the Fluorescence Activated Cell Sorting (FACS). The cytotoxicity of our molecules was concentration-dependent at microgram concentrations Expect for dermaseptin B2 and its derivative which present no toxicity against HeLa and HMC3 cell lines. It was observed that all tested analogs from S4 family exhibited antiviral activity with low concentrations ranging from 3 to 12.5 μg/ml , unlike the native B2 and its derivative which increased the infectivity. Pre-incubating of dermaseptins with ZIKV PF13 before infection revealed that these derivatives inhibit the initial stages of virus infection. In summary, these results suggest that dermaseptins could serve as novel lead structures for the development of potent antiviral agents against Zika virus infections.

The emergence of infections caused by multi-drug resistant bacteria (MDR) to antibiotic treatments poses a significant challenge in the healthcare field. Indeed, the resistance of MDR such as: Klebsiella pneumonia and Staphyloccus epidermidis to antibiotics has become an increasingly concerning issue, especially in hospital settings, necessitating the development of new therapies and more potent antimicrobial agents. Although numerous conventional antibiotic agents have been developed in recent years, but many of them still present toxicity to eukaryotic cells, despite their significant efficacy against multi-resistant microorganisms. Therefore, antimicrobial peptides (AMPs), particularly, dermaseptins (DRSs), are considered promising candidates against MDR, mainly due to their low toxicity and their different mode of action compared to conventional antibiotics. Indeed, these peptides are generally less likely to lead to the resistance phenomena observed for traditional antibiotics. The objectives of this study were to examine the physicochemical and structural properties of peptide derivatives of dermaseptin S4 and B2, and to ascertain their antibacterial potency against Staphylococcus epidermis and Klebsiella pneumoniae. The dermaseptin peptide derivatives used in this study were K₄K₂₀S4, K₄S4(1–16), B2 and K₃K₄B2. In this research, we describe the synthesis and the bioactivity of DRSs and their derivatives against Staphylococcus epidermis and Klebsiella pneumoniae. The cytotoxicity of these compounds was investigated on the HEp-2 cell line by MTT cell viability assay. The cytotoxicity of DRSs was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibited antibacterial activity with Minimum Inhibitory Concentrations (MICs) ranging from 6.25 to 25 μg/ml and Minimum Bactericidal Concentrations (MBCs) ranging from 12.5 to 50 μg/ml. In summary, these findings indicate that dermaseptins could serve as promising lead compounds for the development of potent antibacterial agents targeting infections caused by Klebsiella pneumoniae and Staphylococcus epidermidis.

Healthcare-Associated infections (HAIs) affect more than 100 million patients each year worldwide. These infections are mainly caused by multi-resistant bacterial strains (MDR) such as Acinetobacter Baumanii which is responsible of high mortality rate in immunocompromised individuals. However, the treatment is further aggravated by the abuse of antibiotics, the lack of vaccine and the emergence of resistance posing a huge challenge for the discovery of new therapeutic drugs to overcome this nosocomial infection. In this context, antimicrobial peptides with potential antibacterial proprieties could be an alternative. In this research, we describe the synthesis and the bioactivity of dermaseptins and their derivatives against Acitenobacter baumanii. The cytotoxicity of these DS was investigated on the HEp-2 cell line by the MTT cell viability assay. Thereafter, we studied morphological alterations caused by the action of one of the active peptides on the bacterial membrane using Atomic Force Microscopy (AFM). The cytotoxicity of dermaseptins was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibit antibacterial activity with MICs ranging from 3.125 to 12.5 μg/mL and MBCs ranging from 6.25 to 25 μg/mL. Microscopic images obtained by AFM revealed morphological changes on the surface of treated bacteria caused by K4S4(1-16), as well as significant surface alterations. Overall, these findings demonstrate that DS might constitute new lead structures for the development of potent antibacterial agents against Acinetobacter infections.