Antibiotic resistance is considered a major health concern globally. It is a fact that the clinical need for new antibiotics was not achieved until now. One of the most commonly prescribed classes of antibiotics is β-Lactam antibiotics. However, most bacteria have developed resistance against β-Lactams by producing enzymes β-Lactamase or penicillinase. The discovery of new β-Lactamase inhibitors as new antibiotics or antibiotic adjuvants is essential to avoid future catastrophic pandemics. In this study, five dihydroisocoumarin: 6-methoxy mellein (1); 5,6-dihydroxymellein (2); 6-hydroxymellein (3); 4-chloro-6-hydroxymellein (4) and 4-chloro-5,6-di-hydroxymellein (5) were isolated from Wadi Lajab sediment-derived fungus Penicillium chrysogenum, located 15 km northwest of Jazan, KSA. The elucidation of the chemical structures of the isolated compounds was performed by analysis of their NMR, MS. Compounds 1–5 were tested for antibacterial activities against Gram-positive and Gram-negative bacteria. All of the compounds exhibited selective antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Bacillus licheniformis except compound 3. The chloro-dihydroisocoumarin derivative, compound 4, showed potential antimicrobial activities against all of the tested strains with the MIC value between 0.8–5.3 μg/mL followed by compound 5, which exhibited a moderate inhibitory effect. Molecular docking data showed good affinity with the isolated compounds to β-Lactamase enzymes of bacteria; NDM-1, CTX-M, OXA-48. This work provides an effective strategy for compounds to inhibit bacterial growth or overcome bacterial resistance.

The epidermal growth factor receptor (EGFR), a crucial component of cellular signaling pathways, is frequently dysregulated in a range of cancers. EGFR targeting has become a viable approach in the development of anti-cancer medications. This study employs an integrated approach to drug discovery, combining multiple computational methodologies to identify potential EGFR inhibitors. The co-crystal ligand for the EGFR protein (R85) (PDB ID: 7AEI) was employed as a model for developing pharmacophore hypotheses. Nine databases underwent a ligand-based virtual screening, and 1271 hits meeting the screening criteria were chosen. EGFR protein crystal structure was obtained from the PDB database (PDB ID: 7AEI) and prepared. The hit compounds identified during virtual screening were docked to the prepared EGFR receptor to predict binding affinities by using the glide tool’s standard precision mode. The top ten compounds were chosen, and their affinities of binding ranged from -7.691 to -7.338 kcal/mol. The ADMET properties of the selected compounds were predicted, and three compounds MCULE-6473175764, CSC048452634, and CSC070083626 showed better QPPCaco values compared to other identified compounds, so these were selected for further stability analysis. To confirm the stability of the protein-ligand complexes, a 200 ns molecular dynamics (MD) simulation was run using the binding sites of the top three compounds against the EGFR receptor. These results suggest that the selected compounds may be lead compounds in suppressing the biological activity of EGFR, additional experimental investigation is required.

Pseudo-oligosaccharides are microbial-derived secondary metabolites whose chemical structures contain pseudosugars (glycomimetics). Owing to their high resemblance to the molecules of life (carbohydrates), most pseudo-oligosaccharides show significant biological activities. Some of them have been used as drugs to treat human and plant diseases. Because of their significant economic value, efforts have been put into understanding their biosynthesis, optimizing their fermentation conditions, and engineering their metabolic pathways to obtain better production yields. Many unusual enzymes participating in diverse biosynthetic pathways to pseudo-oligosaccharides have been reported. Various methods and conditions to improve the production yields of the target compounds and eliminate byproducts have also been developed. This review article describes recent studies on the biosynthesis, fermentation optimization, and metabolic engineering of high-value pseudo-oligosaccharides.

Polymorphism in cytochrome P450 (CYP) 2C9 enzyme is known to cause significant inter-individual differences in drug response and occurrence of adverse drug reactions. Different alleles of the CYP2C9 gene have been identified, but the notable alleles responsible for reduced enzyme activity are CYP2C9*2 and CYP2C9*3. No pharmacogenetic data are available on CYP2C9*2 and CYP2C9*3 alleles in the Pakistani population. In Pakistan, pharmacogenetics, which examines the relationship between genetic factors and drug response, are in the early stages of development. We, for the first time, investigated the association between the CYP2C9 variant alleles CYP2C9*2 and CYP2C9*3 and the incidence of hypoglycaemia in patients with Type 2 diabetes mellitus (T2DM) receiving sulphonylurea medications. A total of n = 400 individuals of Pashtun ethnicity were recruited from 10 different districts of Khyber Pakhtunkhwa, Pakistan to participate in the study. The study participants were divided into two distinct groups: the case group (n = 200) and the control group (n = 200). The case group consisted of individuals with T2DM who were receiving sulphonylurea medications and experienced hypoglycaemia with it, whereas the control group included individuals with T2DM who were receiving sulphonylurea medication but did not experience sulphonylurea-induced hypoglycaemia (SIH). Blood samples were obtained from study participants following informed consent. DNA was isolated from whole blood samples using a Wiz-Prep DNA extraction kit. Following DNA isolation, CYP2C9 alleles were genotyped using MassARRAY sequencing platform at the Centre of Genomics at the Rehman Medical Institute (RMI). The frequency of CYP2C9*2 (low-activity allele) was more frequent in the diabetic patients with SIH compared to the control group (17.5% vs. 6.0%, p = 0.021). The frequency of its corresponding genotype CYP2C9*1/*2 was higher in cases compared to the control group (10% vs. 6% with p = 0.036); the same was true for genotype CYP2C9*2/*2 (7% vs. 3.5% with p = 0.028). Logistic regression analysis evidenced potential association of CYP2C9*2 allele and its genotypes with SIH. When adjusted for confounding factors such as age, weight, sex, mean daily dose of sulphonylurea, and triglyceride level, the association between the CYP2C9*2 allele and hypoglycaemia remained consistent. Confounding factors played no role in SIH (insignificant p-value) because both groups (cases and controls) were closely matched in term of age, weight, sex, mean daily dose of sulphonylurea, and triglyceride levels. Our study suggests that genetic information about a patient’s CYP2C9 gene/enzyme can potentially assist physicians in prescribing the most suitable and safest drug, based on their genetic make-up.

Abdullah R Alanzi. J. Microbiol. Biotechnol. 2025;35:. https://doi.org/10.4014/jmb.2407.07064