An anti-neurodegeneration activity study was carried out for 80 flavonoid compounds. The structure–activity analysis of the structures was carried out by performing three different anti-neurodegeneration screening tests, showing that in these structures, the presence of a hydroxy substituent group at position C3′ as well as C5′ of ring B and a methoxy substituent group at the C7 position of ring A play a vital role in neuroprotective and antioxidant as well as anti-inflammatory activity. Further, we found structure (5) was the top-performing active structure out of 80 structures. Subsequently, a molecular docking study was carried out for the 3 lead flavonoid compounds (4), (5), and (23) and 21 similar hypothetical proposed structures to estimate the binding strength between the tested compounds and proteins potentially involved in disease causation. Ligand-based pharmacophores were generated to guide future drug design studies.

Marine biofouling is the undesired accumulation of organic molecules, microorganisms, macroalgae, marine invertebrates, and their by-products on submerged surfaces. It is a serious challenge for marine vessels and the oil, gas, and renewable energy industries, as biofouling can cause economic losses for these industries. Natural products have been an abundant source of therapeutics since the start of civilisation. Their use as novel anti-fouling agents is a promising approach for replacing currently used, harmful anti-fouling agents. Anthraquinones (AQs) have been used for centuries in the food, pharmaceutical, cosmetics, and paint industries. Citreorosein and emodin are typical additives used in the anti-fouling paint industry to help improve the global problem of biofouling. This study is based on our previous study, in which we presented the promising activity of structurally related anthraquinone compounds against biofilm-forming marine bacteria. To help uncover the anti-fouling potential of other AQ-related structures, 2194 compounds from the COCONUT natural products database were analysed. Molecular docking analysis was performed to assess the binding strength of these compounds to the LuxP protein in Vibrio carchariae. The LuxP protein is a vital binding protein responsible for the movements of autoinducers within the quorum sensing system; hence, interrupting the process at an early stage could be an effective strategy. Seventy-six AQ structures were found to be highly docked, and eight of these structures were used in structure-based pharmacophore modelling, resulting in six unique pharmacophore features.

Bovine mastitis is a worldwide disease affecting dairy cattle and causes major economic losses in the dairy industry. Recently, the emergence of microbial resistance to the current antibiotics complicates the treatment protocol which necessitates antibiotic stewardship and further research to find new active compounds. Recently, phytobiotics have gained interest in being used as an alternative to antibiotics in the poultry industry as an antibiotic stewardship intervention. This study evaluated the in vitro antibacterial activity of 16 flavonoids against bovine mastitis pathogens. Two flavones: 2-(4-methoxyphenyl)chromen-4-one (1) and 2-(3-hydroxyphenyl)chromen-4-one (4) showed inhibition of the growth of Klebsiella oxytoca with MIC values range (25–50 µg mL^− 1) followed by a structure-activity relationship (SAR) study indicating that the presence of a hydroxyl group at C-3` or methoxy at C-4` increases the activity against Klebsiella oxytoca while the presence of hydroxyl group at C-7 decreases the activity. Furthermore, a structure-based drug development approach was applied using several in silico tools to understand the interactions of active flavones at the active site of the DNA gyrase protein. Compound (4) showed a higher docking score than quercetin (standard) which is known to have antibacterial activity by inhibiting the DNA gyrase. In addition, the structure-based pharmacophores of compound (4) and quercetin showed similar pharmacophoric features and interactions with DNA gyrase. Based on our findings, compounds (1) and (4) are promising for further study as potential anti-microbial phytochemicals that can have a role in controlling bovine mastitis as well as to investigate their mechanism of action further.

Mpox is a globally prevalent disease that has triggered multiple epidemics over the past few decades, leading to moderate rates of hospitalisation and mortality. Recently, it has re-emerged in several countries, including the Democratic Republic of Congo, and appears to be spreading at an unprecedented pace. The disease is caused by zoonotic double-stranded DNA viruses. Due to its similarities with smallpox, distinguishing between the two can be challenging, though the smallpox vaccine typically provides immunity against Mpox. At the time of writing, no approved treatment for Mpox exists; however, several promising candidates have demonstrated the ability to inhibit viral replication, including resveratrol—a polyphenolic compound found in red wine. This study employs molecular docking and molecular dynamics simulations to assess the effectiveness and stability of nine resveratrol analogues. Additionally, 2D and 3D pharmacophore models were developed for the highest-ranked docked compounds, leading to a composite pharmacophore. A structure–activity relationship analysis was also conducted using these top-performing compounds. The findings suggest that two compounds— (9) [1,1'-biphenyl]-3,4',5-triol and (11) {3-hydroxy-5-[2-(4-hydroxyphenyl)ethenyl]phenyl}oxidanesulfonic acid—exhibit strong binding affinity, with compound 11 potentially forming a stable complex with the thymidylate kinase of the vaccinia virus. Graphical abstract

Cowpox is caused by a DNA virus known as the cowpox virus (CPXV) belonging to the Orthopoxvirus genus in the family Poxviridae. Cowpox is a zoonotic disease with the broadest host range among the known poxviruses. The natural reservoir hosts of CPXV are wild rodents. Recently, the cases of orthopoxviral infections have been increasing worldwide, and cowpox is considered the most common orthopoxviral infection in Europe. Cowpox is often a self-limiting disease, although cidofovir or anti-vaccinia gammaglobulin can be used in severe and disseminated cases of human cowpox. In this computational study, a molecular docking analysis of thymine- and arabinofuranosyl-thymine-related structures (1–21) on two cowpox-encoded proteins was performed with respect to the cidofovir standard and a 3D ligand-based pharmacophore model was generated. Three chemical structures (PubChem IDs: 123370001, 154137224, and 90413364) were identified as potential candidates for anti-cowpox agents. Further studies combining in vitro and in silico molecular dynamics simulations to test the stability of these promising compounds could effectively improve the future design of cowpox virus inhibitors, as molecular docking studies are not sufficient to consider a ligand a potential drug.

Natural products from marine and terrestrial organisms provide an important resource for medicinal chemistry and drug discovery. Defined as occurring at depths greater than 200 m, most of the ocean, by area and volume, is comprised of deep-sea environments. These contrasting ecosystems exhibit a wide range of temperature, pressure, and environmental chemistry conditions that harbour high phylogenetic diversity. Here we analyse the global distribution of Marine Natural Products (MNPs) from deep-sea organisms, which reveals chronic undersampling of the deep ocean as a reservoir of new and diverse chemical structures and bioactivity. The sources of 2909 compounds and extracts, compiled from published records, show a sampling bias towards benthic and shallower deep-sea habitats, with relatively few from areas beyond national jurisdictions and a concentration of records along geomorphological features that have been the focus of marine scientific interest such as seamounts and hydrothermal vents. The phylogenetic distribution of deep-sea MNPs is dominated by non-metazoan sources (76% of records) and Ascomycota fungi in particular (55%). Polyketides are the most prevalent metabolites in deep-sea MNPs, and cytotoxic and antibacterial properties are the most commonly reported bioactivities. Our analyses highlight a need for systematic sampling and consistent data reporting to explore potential relationships, if any, between, bioactivity, new chemical structures, phylogeny and deep-sea environmental conditions, which could guide targeted biodiscovery in our planet’s largest biome and enable better assessment of the benefits of protecting deep-sea biodiversity from human impacts.