This study outlines the synthesis and both experimental and theoretical characterization of novel 5-(4-arylazo-3-methyl-1H-pyrazol-5-ylazo)-4-hydroxy-6-methyl-1H-pyrimidin-2-one dyes (3a-3e). Aniline and 4-substituted aniline derivatives, along with 3-aminocrotonitrile, were used as starting materials. The intermediates underwent cyclization with hydrazine monohydrate to produce mono-azo dyes (2a-2e), which were then diazotized. The resulting salts were reacted with ethyl acetoacetate to obtain intermediates. These intermediates were subsequently reacted with urea in the presence of heat to obtain the desired dyes (3a-3e). The synthesized dyes were characterized via FT-IR and H-1-NMR spectroscopy for their structural confirmation. The effects of various solvents (six in number), substituents and acid-base characteristics were examined via UV-Vis spectroscopy. Furthermore, DFT calculations were performed to investigate the electronic structure and reactivity of the compounds, and the results were compared with experimental findings. Computational analyses included localized orbital locator (LOL), electron localization function (ELF), and density of states (DOS) analyses to explore the electronic structure of the compounds. Intermolecular interactions, specifically hydrogen bonding and van der Waals interactions, were identified and examined via non-covalent interaction (NCI) analysis as well as reduced density gradient analysis. As per HOMO-LUMO energy gap of compounds, it is found that dye 3c was found to have a softer electronic character and higher reactivity. In addition to DFT, a purely computational molecular docking analysis was performed using Thymidylate Kinase receptor (PDB, 4qgg) to provide an in silico prediction of the possible antibacterial relevance of the compounds. The binding affinity of dye 3c was calculated as -8.2 kcal/mol. However, all biological interpretations in this study are purely computational and lack experimental validation. The reliability of the docking results and the stability of the complexes were further supported through 100 ns molecular dynamics (MD) simulations. The results of this study indicate that compound 3c may be a promising candidate for future research; however, its antibacterial activity remains a theoretical prediction requiring experimental confirmation.
Breast cancer is the most prevalent cancer among women globally, with an increasing incidence in countries like India. Despite the established histopathological classification of breast cancer, its heterogeneity poses challenges in predicting patient outcomes and selecting appropriate treatments. Recent advancements in molecular biology have led to the development of molecular subtypes of breast cancer, which provide a more precise prognostic assessment. This study aims to correlate histopathological features with molecular subtypes using immunohistochemical (IHC) markers to improve the accuracy of breast cancer diagnosis and treatment. A cross-sectional, observational study was conducted on 500 primary breast carcinoma patients diagnosed between January 2020 and January 2024. Patients were categorized based on clinical features, histopathological findings, and molecular subtypes determined by IHC markers for estrogen receptor (ER), progesterone receptor (PR), HER2, Ki67, epidermal growth factor receptor (EGFR), and CK 5/6. The molecular subtypes identified included Luminal A, Luminal B, HER2-enriched, and Basal-like (triple-negative), with histopathological features such as tumor grade, size, lymphovascular invasion (LVI), and lymph node involvement also recorded. Showed that Luminal A tumors were associated with lower tumor grades, smaller sizes, and less aggressive features. In contrast, HER2-enriched and Basal-like subtypes demonstrated more aggressive behavior, with higher tumor grades, larger sizes, and increased rates of metastasis. Statistically significant correlations were found between molecular subtypes and histopathological features (p < 0.05). Immunohistochemical markers like HER2, Ki67, and EGFR were key in determining tumor aggressiveness and treatment planning. This study emphasizes integrating molecular subtyping with histopathological evaluation to personalize breast cancer treatment. By identifying the molecular characteristics of tumors, clinicians can optimize therapeutic strategies, reduce unnecessary chemotherapy, and improve patient outcomes. These findings advocate for using molecular profiling in clinical practice to enhance breast cancer diagnosis and treatment strategies.
Introduction: Carbonic Anhydrase II (CA-II) is crucial for several physiopathological processes, including bone calcification, osteoporosis, tumorigenicity, and epilepsy, among others. Usually, the intraocular pressure observed in glaucoma exacerbates the condition, and CA-II inhibitors have the potential to be used for the reduction of this pressure. Methods: Moreover, to search for novel CA-II inhibitors with high potency, a series of hydrazonothiazoline derivatives (5a-q) were synthesized. The inhibitory potency of our synthesized compounds was investigated for human and bovine CA-II through in-vitro and computational methods. The in vitro screening revealed that 5a-5f, 5g, 5h, and 5l have significant inhibitory action for bCA-II (IC50 = 13.1 μM to 44.6 μM), whereas 5a, 5d, 5f, 5h, and 5l exhibited excellent inhibition of hCA-II (IC50 = 7.0 μM to 33.1 μM). Therefore, binding pattern of those active hits was elucidated by in silico docking, which reflects that the thiazole group of ligands is responsible for binding of compounds with the target proteins and consequent functional inhibition of the enzyme. Moreover, the type of inhibition of active hits (5a and 5h for hCA-II and bCA-II, respectively) was explored by kinetics experiment in which both 5a (for hCA-II, Ki = 5.25±0.004 μM) and 5h (for bCA-II, Ki = 5.5±0.001 μM) competitively inhibited CA-II. Results: The molecular dynamics simulation, MMPBSA analysis, revealed that 5a has better stability in 1BN1 than 5h in 1V9E. Conclusion: Those identified inhibitors could serve as a skeleton to design more potent CA-II inhibitors in the future.
The present study involves the formulation and evaluation of a topical herbal cream incorporating Spathodea campanulata (African tulip tree) flower extract. Spathodea campanulata, native to tropical Africa, is widely recognized in traditional medicine for its therapeutic properties, particularly in the treatment of wounds, inflammation, and microbial infections. The vibrant orange-red flowers of the plant are known to be rich in bioactive phytochemicals such as flavonoids, tannins, saponins, and phenolic compounds, which contribute to their antioxidant, anti-inflammatory, and antimicrobial effects. Fresh flowers were collected and subjected to Soxhlet extraction using ethanol to obtain a concentrated extract. The extract was then incorporated into a cream base composed of paraffin, beeswax, borax, methylparaben, and rose oil. The formulated cream was evaluated for key physicochemical characteristics such as pH, spreadability, viscosity, homogeneity, and stability. Organoleptic evaluation confirmed the product's acceptable color, texture, and odour. The cream showed suitable consistency for topical application and did not cause any irritation during the skin irritancy test. Antimicrobial activity was assessed using the agar well diffusion method against selected bacterial strains. The extract demonstrated dose-dependent inhibitory activity, particularly against Gram-positive bacteria. These findings are consistent with the traditional use of Spathodea campanulata in managing skin infections and promoting wound healing. In conclusion, the formulated herbal cream exhibited good physical stability, safety, and antimicrobial potential. The study highlights the therapeutic value of Spathodea campanulata flowers and supports their incorporation into natural, skin-friendly topical formulations.
Micronutrient deficiencies in soils are a critical challenge in agriculture, particularly in acidic soil environments where nutrient availability is strongly limited by fixation, leaching, and altered metal speciation. These constraints contribute to inefficient nutrient uptake and reduced crop yields. Conventional micronutrient supplementation methods are often inefficient, environmentally harmful, and unsustainable, underscoring the need for smarter delivery systems tailored to soil pH conditions. In this study, we developed biodegradable, pH-responsive microbeads from κ-carrageenan (κ-CG) and trans-ferulic acid (TFA) for targeted micronutrient release. The κ-CG-TFA microbeads were synthesized via an eco-friendly process and optimized for size, morphology, stability, and nutrient retention. Characterization confirmed the successful incorporation of functional groups, while swelling, degradation, and release studies demonstrated efficient delivery of essential micronutrients (Zinc, Manganese, Iron, Copper,) under acidic conditions (pH 4.0), mimicking acidic soil environments. The inherent antioxidant activity of TFA conferred strong radical-scavenging capacity, further enhancing its functionality. Soil water and plant growth assays revealed that the microbeads improved micronutrient availability, significantly increased chlorophyll content and leaf area, promoted vigorous seedling growth, and caused no phytotoxic effects. Collectively, these findings establish κ-CG-TFA microbeads as a promising, eco-friendly platform for sustainable micronutrient delivery and stress reduction, thereby improving crop productivity in agriculture. ### Competing Interest Statement The authors have declared no competing interest. Indian Institute of Technology Gandhinagar, https://ror.org/0036p5w23, IP/IITGN/BE/MD/2223/13, IP/IITGN/BE/SS/2223/17 Department of Biotechnology, https://ror.org/03tjsyq23, RES/DBTRL/BE/PO369/2223/0018
