Current Topics in Medicinal Chemistry - Online First

Although E. coli is considered a normal human microbiota, it may cause life-threatening infections such as septicemia, urinary tract infections, and enteric infections. Moreover, multidrug-resistant strains are a serious challenge in the clinic due to high mortality rates and the limited number of therapeutic options. Hence, the current study aimed to benefit from pink rose petals as a source of green synthesis of copper nanoparticles (Cu-NPs), to investigate the antibacterial features against multidrug-resistant E. coli, and to measure the cytotoxicity of Cu-NPs.

Pink rose petals were used as a reducing agent for Cu-NP synthesis, and then XRD, zeta potential, UV-Vis, FTIR, SEM, and DLS analyses were performed to characterize the synthesized NPs. Moreover, the MIC and zone of inhibition values of Cu-NPs were measured and compared to common antibiotics. Additionally, the MTT assay was performed to assess the cytotoxicity.

The green synthesized Cu-NPs were spherical and uniform with a size of ~200 nm. The MIC of Cu-NPs was 1024 μg/ml on the MDR strain of E. coli, representing the antibacterial activity comparable to levofloxacin (p-value>0.05) but less than imipenem and trimethoprim (p-value<0.001). Moreover, the CC50 of synthesized Cu-NPs was 731.2 μg/ml and significantly lower than the studied antibiotics (p-value<0.001).

The findings may suggest Cu-NPs as a promising antibacterial strategy against MDR strains of E. coli, however, further studies are encouraged to clarify the safety of optimized doses.

Breast cancer has become the most commonly diagnosed cancer worldwide and represents a major burden to public health. Advances in understanding ferroptosis pathways and identifying new therapeutic targets raise hope for using ferroptosis modulators to treat untreatable diseases.

In this study, BALB/c mice were divided into several groups: model, Doxorubicin-treated, FINO2-treated, Pirfenidone-treated, and a combined Pirfenidone + FINO2 group. After treatment, we assessed iron content in cancer cells, fibrosis area, CD34 expression, and mRNA levels of solute carrier family 7 member 11(SLC7A11) and heme oxygenase 1 (HMOX1).

Results showed that the average tumor size in the Pirfenidone + FINO2 group was significantly smaller than in the doxorubicin group. Treatments with FINO2, Pirfenidone, or their combination significantly increased iron content in cancer cells and reduced the fibrosis area. Co-treatment with FINO2 and Pirfenidone also led to notable decreases in CD34 expression and mRNA levels of SLC7A11 and HMOX1.

These findings suggest that FINO2 ferroptosis agonists, when combined with other anticancer agents like Pirfenidone, can enhance ferroptosis and reduce tumor fibrosis. Additionally, the overexpression of SLC7A11 and HMOX1 in breast cancer model mice is associated with increased tumor growth and reduced metastasis, indicating that targeting these proteins with specific inhibitors may be a promising strategy for breast cancer treatment.

New antibacterial agents are urgently needed as bacterial diseases, especially urinary tract infections (UTIs), are becoming more common, and antibiotic resistance is increasing.

This study aimed to design, synthesize, and conduct molecular docking and biological evaluation of pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones as antibacterial agents.

7-Phenyl-5-(thiophen-2-yl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones were designed using an in silico approach. The designed compounds were synthesized using reported procedures. Molecular docking studies were carried out using the Maestro 12.9 module of Schrodinger software. QikProp module of the Schrodinger suite was used for in silico ADME evaluation of synthesized compounds. In vitro antibacterial activity of these compounds was assessed using the serial dilution method.

Compounds MA-03 and MA-12 showed potent antibacterial activity with MIC values of 1.56, 3.125, 1.56, and 6.25 µg/ml and 1.56, 3.12, 6.25, and 3.12 µg/ml, respectively, against Bacillus subtilis, Staphylococcus aureus, Pseudomonas putida, and Escherichia coli using controls ciprofloxacin and amoxicillin (0.78, 0.39, 1.56 and 0.39 µg/ml and 0.78, 3.125, 3.125, and 1.56 µg/ml). All the synthesized compounds demonstrated higher binding affinities against bacterial proteins with reference to amoxicillin and ciprofloxacin.

All the compounds exhibited antibacterial activity against all the tested strains of bacteria with optimum ADME profile.

Synthetic drugs are the drug of choice for topical treatment of psoriasis. However, these are associated with side effects; hence, there is a need to explore effective alternative treatments for psoriasis. Jasminum auriculatum has been used in Ayurvedic and traditional medicine as an ingredient for managing numerous skin ailments like eczema and ringworm.

This study aimed to evaluate the in vivo study of ointments prepared from chloroform and methanolic extracts of Jasminum auriculatum for the treatment of psoriasis.

Initially, pharmacogenetic and physicochemical characterization of Jasminum auriculatum was performed to check their presence. The ointments prepared from chloroform and methanolic extracts of Jasminum auriculatum were screened for acute toxicity studies and antipsoriatic activity by IMQ-induced psoriasis in the Swiss albino mice ear model. The parameters like ear thickness, ear weight, erythema, scales, and infiltration (Permeation into the skin) were evaluated. The histopathological studies were also conducted to support the findings.

The plant showed the presence of pharmacogenetic structures like Trichomes, Palisade cells, Xylem, Collenchyma Tous cells, Parenchymatous cells, Fibers, Pericyclic cells, Stomata, Phloem, and Sclerenchyma Tous cells responsible for the presence of phytoconstituents having antipsoriatic activity. The signs and symptoms increased in imiquimod-induced animals, but ointment of chloroform and methanolic extract of Jasminum auriculatum reduced the skin thickness, redness, scaling, and erythema. The study reveals along with the progression of disease topical formulation of the extract showed the effect on animals in a dose-dependent manner. Histopathological examination also supported the earlier results.

The present study demonstrates that ointments of chloroform and methanolic extract of Jasminum auriculatum are safe and effective in the treatment of psoriasis, as revealed by the in vivo study. These preclinical results could further be explored for the development of other topical formulations used in humans.

Exploring the correlation between ovarian cancer and aging has great significance for understanding the pathogenesis of ovarian cancer and formulating targeted therapeutic regimens.

This computational study aims to identify and validate key genes in monocyte subtypes related to ovarian cancer and aging, exploring potential causal relationships.

We collected single-cell RNA sequencing data (GSE157007, GSE184880), GWAS data (14,049 samples and 40,941 controls from a European population), and eQTL data of ovarian cancer and aging. Using R software packages like Seurat and singleR, we conducted data integration, quality control, cell classification, and differential gene expression analysis to identify intersecting monocyte subtype genes in ovarian cancer and aging. We employed summary data-based Mendelian randomization (SMR) analysis and Heterogeneity in Dependent Instruments (HEIDI) tests to pinpoint causal genes. Further single-cell functional analyses (gene switching, cell communication, metabolic pathway analysis), Bulk RNA sequencing validation, functional enrichment, and protein-protein interaction (PPI) analyses elucidated these genes' biological roles.

The dataset included 123,280 cells, revealing differential gene expression in classical monocytes (104 genes), intermediate monocytes (43 genes), and myeloid dendritic cells (39 genes). SMR and HEIDI identified causal relationships for 7 genes in classical monocytes, 3 in intermediate monocytes, and 3 in myeloid dendritic cells with ovarian cancer. Bulk RNA seq validation confirmed six monocyte genes as causal in ovarian cancer and aging. TREM1, SERPINB2, and CD44 were upregulated, while DST was downregulated; SLC11A1 and PNRC1 showed contradictory patterns. Interactions with NK and T cells involved LGALS9 - CD44/45 receptors. Riboflavin metabolism was a common enriched pathway.

This study identified six specific monocyte genes as potential therapeutic targets for ovarian cancer and aging.

Skin cancer is one of the most prevalent cancers globally and is considered a serious public health problem associated with high death rates. The current therapeutic regimes for skin cancer are limited by their low bioavailability, generation of resistance, or adverse side effects. Many fruit extract-based nutraceuticals hold potential as topical treatment methods. Pyrus communis (Pear) fruit extract is a rich source of cholinergic acid, presently used as therapy for various skin diseases. Thus, it qualifies as a promising candidate for skin cancer treatment.

The objective of the study is to evaluate the cytotoxicity of Pyrus communis extract entrapped in ethosomes.

In this study, Pyrus communis fruit extract was formulated in ethosomes using the hot method and optimized using central composite design. The optimized ethosomes were characterized in vitro for particle size distribution, zeta potential, entrapment efficiency, morphology, and particle stability.

Preliminary phytochemical screening results suggest that PCHE contains a significant amount of phenolic compounds compared to other extracts (PCEA and PCAE). The presence of these phenolic compounds contributes to the strong antioxidant and cytotoxic effects of PCHE, which are observed in a dose-dependent manner. Analysis through GC-MS has identified chlorogenic acid, arbutin, ursolic acid, quercetin, and epicatechin are present in PCHE. Based on the initial testing of the extracts, PCHE was chosen for the preparation of ethosomes. The optimized ethosomes were found to have a particle size of 699 nm and a zeta potential of -16.07. Transmission Electron Microscopy illustrated a closed, spherically symmetrical structure of the ethosomes. Additionally, the Franz diffusion cell analysis for percutaneous absorption using egg membrane indicated a steady-state flux of the drug from the ethosomes. The formulation's cytotoxicity potential was assessed using the epidermoid carcinoma cell line (A431) through the MTT assay. The results show that the ethosome formulations exhibit cytotoxic activity better than PCHE extract. 1

In sum, the result of this study clearly points out that Pyrus communis extract entrapped in ethosomes, prepared by hot method, displayed a cytotoxic potential against skin cancer cell lines. This ethosomal formulation can be harnessed for skin cancer therapy through further mechanistic analysis and animal studies.