Current Topics in Medicinal Chemistry - Online First

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.

MMP1 (matrix metallopeptidase 1) plays a significant role in the degradation of collagen fibres within the extracellular matrix, and has been linked to a multitude of biological processes, including rheumatoid arthritis, osteoarthritis, periodontal disease, and tumor invasion.

In order to discover inhibitors of MMP1 that originate from the phytochemicals of the dandelion (Taraxacum mongolicum Hand.-Mazz.).

The herbal constituents of the dandelion were retrieved from the HERB database. A multifaceted approach including molecular docking, MMP1 enzyme assays, and molecular dynamics simulations was used to identify potential MMP1 inhibitors among the chemical compounds present in the dandelion.

A total of 61 chemical constituents of the dandelion were collated from the HERB database. A potential MMP1 inhibitor was identified through a combination of molecular docking and an MMP1 enzyme bioactivity assay. Cichoric acid demonstrated pronounced inhibitory activity against MMP1, with an IC50 value of 7.81 ± 2.60 μM. Molecular dynamics simulations and binding free energy calculations indicated that the nonpolar interaction energies of LEU181, ARG214, VAL215, HIS218, GLU219, HIS228, PRO238, and SER239 played a primary role in the binding of cichoric acid to MMP1.

The integration of molecular modeling and bioactivity testing proved an effective method for the rapid discovery of targeted small molecule inhibitors. Cichoric acid demonstrated potent MMP1 inhibitory activity and thus represented a promising candidate for further development.

Globally, breast cancer (BC) affects a greater number of women than any other kind of cancer, and it is the second leading cause of death after lung cancer. The current standard of care for cancer treatment is the surgical excision of the malignant tumor followed by adjuvant therapy with chemotherapy or radiation. Regrettably, the side effects of radiation and chemotherapy frequently cause harm to healthy tissues and organs, hence limiting the effectiveness of these treatments in addressing BC. Recently, various nanoparticles (NPs) have been discovered and manufactured with the capacity to selectively target cancerous cells while minimizing harm to normal cells or organs. As a result, the utilization of NPs-mediated targeted drug delivery systems (DDS) has emerged as a promising method for treating BC.

The primary aim of this review was to provide a concise overview of the function of different nanoparticles in the specific delivery of anticancer medications to eradicate breast cancer.

The present review paper performed a literature inspection using several search engines such as PubMed, Google Scholar, and Science Direct.

In addition to their ability to selectively target tumor cells and minimize side effects, nanoparticles (NPs) possess other distinctive characteristics that make them highly desirable for cancer treatment. These include low toxicity, excellent compatibility, ease of preparation, high photoluminescence for in vivo bioimaging, and the capacity to efficiently load drugs due to their adjustable surface functionalities.

This study provides a comprehensive examination of recent therapeutic studies that utilize various nanoparticle-mediated drug delivery systems as alternatives to established therapy techniques for breast cancer. This study will elucidate the importance of nanoparticle-mediated drug delivery systems (DDS) and provide a roadmap for identifying the optimal approach for future targeted drug delivery, specifically for the treatment of breast cancer.

Cellular aging is a complicated event known for gradually reducing homeostasis, leading to a higher susceptibility to diseases and mortality. Since the behavior of Hematopoietic Stem Cells (HSCs) is potentially affected by plasma-derived exosomes, this study aimed to investigate whether the plasma-derived exosome of young and elderly human donors can deliver “youth” or “aging” signals into human umbilical cord blood-derived HSCs in vitro.

Exosomes were isolated from four young (Y-exo) and four old (O-exo) donors. Umbilical cord blood-derived HSCs were exposed to two concentrations of exosomes (5 and 10 μg/mL). Then, lineage differentiation (CD41 and CD38), the mRNA and protein expression of IL-1β and IL-6, and NFκB activity were evaluated using flow cytometry, qRT-PCR Enzyme-Linked Immunosorbent Assay (ELISA) methods, and western blot techniques, respectively.

The lineage-specific markers CD41 and CD38 expression were increased after exposure to O-exo compared to Y-exo at the concentration of 10 μg/mL (P<0.001). The HSCs treated with 10 μg/mL O-exo increased protein and mRNA expression of IL-1β and IL-6 compared to Y-exo at 10 μg/mL concentration (P<0.01). Furthermore, a significant difference was seen in p-NF-κB levels between O-exo and Y-exo at the concentration of 10 μg/mL (P=0.0014).

Our findings advocated the concept that circulating exosomes of old and young individuals may differently affect the pathways involved in the aging process in HSCs.Therefore, exosomes may be applied as therapeutic agents for regenerative medicine.

This study aims to isolate and evaluate the anticancer potential of laccaic acids from lac dye by utilizing polarity-based fractionation and high-performance liquid chromatography (HPLC).

In this study, polarity-based fractionation of lac dye was performed to isolate its constituents. A novel HPLC method was developed for the chromatographic separation of lac dye components, utilizing gradient elution with two solvents: 0.1% (v/v) formic acid in LCMS-grade water (A) and 90:10 acetonitrile HPLC-grade (B) at a flow rate of 0.4 mL/min. This method facilitated the isolation of four key constituents: laccaic acid D, laccaic acid B, laccaic acid C, and laccaic acid A.

The purity of these compounds was confirmed via LCMS methods. The anticancer activity of the isolated constituents was evaluated against the MDA-MB-231 cell line using the MTT assay. Notably, laccaic acid A demonstrated significant anticancer activity with an IC50 value of less than 100 nM, comparable to that of Adriamycin. Further investigations into the apoptotic activity of laccaic acid A were conducted using flow cytometry, revealing that laccaic acid A is a non-necrotic and apoptotic inducer. Additionally, considering that an effective anticancer agent may also exhibit antioxidant, anti-inflammatory, and anti-angiogenesis properties, the isolated laccaic acids were accessed for these biological activities.

The results were promising, indicating that laccaic acids could offer a multifaceted approach to cancer treatment. This study highlights the potential of laccaic acids as valuable candidates for anticancer therapy and warrants further investigation into their mechanisms of action and therapeutic efficacy.