Evaluation of anticancer potential of tetracene-5,12-dione (A01) and pyrimidine-2,4-dione (A02) via caspase 3 and lactate dehydrogenase cytotoxicity investigations.

Cancer stands as a significant global cause of mortality, predominantly arising from the dysregulation of key enzymes and DNA. One strategic avenue in developing new anticancer agents involves targeting specific proteins within the cancer pathway. Amidst ongoing efforts to enhance the efficacy of anticancer drugs, a range of crucial medications currently interact with DNA at the molecular level, exerting profound biological effects. Our study is driven by the objective to comprehensively explore the potential of two compounds: (7S,9S)-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione (A01) and 5-fluoro-1H-pyrimidine-2,4-dione (A02). These compounds have demonstrated marked efficacy against breast and cervical cancer cell lines, positioning them as promising anticancer candidates. In our investigation, A01 has emerged as a particularly potent candidate, with its potential bolstered by corroborative evidence from lactate dehydrogenase release and caspase-3 activity assays. On the other hand, A02 has exhibited remarkable anticancer potential. To further elucidate their molecular mechanisms and interactions, we employed computational techniques, including molecular docking and molecular dynamics simulations. Notably, our computational analyses suggest that the A01-DNA complex predominantly interacts via the minor groove, imparting significant insights into its mechanism of action. While earlier studies have also highlighted the anticancer activity of A01, our research contributes by providing a deeper understanding of its binding mechanisms through computational investigations. This knowledge holds potential for designing more effective drugs that target cancer-associated proteins. These findings lay a robust groundwork for future inquiries and propose that derivatives of A01 could be synthesized as potent bioactive agents for cancer treatment. By elucidating the distinctive aspects of our study's outcomes, we address the concern of distinguishing our findings from those of prior research.

Synthesis, biological evaluation and in silico investigations of benzotriazole derivatives as potential inhibitors of NIMA related kinase.

In the current study, a novel compound, bis(3-(2H-benzo[d][1,2,3]triazol-2-yl)-2-(prop-2-yn-1-yloxy)-5-(2,4,4-trimethylpentan-2-yl)phenyl)methane (TAJ1), has been synthesized by the reaction of 6,6'-methylenebis(2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol) (1), propargyl bromide (2) and potassium carbonate. Spectroscopic (FTIR, 1H-NMR, 13C-NMR) and single-crystal assays proved the structure of the synthesized sample. XRD analysis confirmed the structure of the synthesized compound, showing that it possesses two aromatic parts linked via a -CH2 carbon with a bond angle of 108.40°. The cell line activity reported a percent growth reduction for different cell types (HeLa cells, MCF-7 cells, and Vero cells) under various treatment conditions (TAJ1, cisplatin, and doxorubicin) after 24 hours and 48 hours. The percent growth reduction represents a decrease in cell growth compared to a control condition. Furthermore, density functional theory (DFT) calculations were utilized to examine the frontier molecular orbitals (FMOs) and overall chemical reactivity descriptors of TAJ1. The molecule's chemical reactivity and stability were assessed by determining the HOMO-LUMO energy gap. TAJ1 displayed a HOMO energy level of -0.224 eV, a LUMO energy level of -0.065 eV, and a HOMO-LUMO gap of 0.159 eV. Additionally, molecular docking analysis was performed to assess the binding affinities of TAJ1 with various proteins. The compound TAJ1 showed potent interactions with NEK2, exhibiting -10.5 kcal mol-1 binding energy. Although TAJ1 has demonstrated interactions with NEK7, NEK9, TP53, NF-KAPPA-B, and caspase-3 proteins, suggesting its potential as a therapeutic agent, it is important to evaluate the conformational stability of the protein-ligand complex. Hence, molecular dynamics simulations were conducted to assess this stability. To analyze the complex, root mean square deviation (RMSD) and root mean square fluctuation analyses were performed. The results of these analyses indicate that the top hits obtained from the virtual screening possess the ability to act as effective NEK2 inhibitors. Therefore, further investigation of the inhibitory potential of these identified compounds using in vitro and in vivo approaches is recommended.

Puerarin-coated gold nanoparticles (PUE-AuNPs) synthesized via green synthetic route: a new colorimetric probe for the detection of ciprofloxacin.

Puerarin-coated gold nanoparticles (PUE-AuNPs) synthesized via green synthetic route, a new colorimetric sensor, efficiently detected the ciprofloxacin (CP) in tap water and cow milk samples. The PUE-AuNPs were characterized by UV-visible, FTIR, AFM, and DLS techniques and were found to be spherical with an average size of approximately 19-20 nm. FTIR spectrum confirms that functional groups such as -OH, -C=O, -CO and -C=C were responsible for the reduction of gold (III) chloride trihydrate. These functional groups acted as capping agents to form AuNPs. The PUE-AuNPs sensor was proved to be selective and sensitive for the detection of CP through colorimetric method within the concentration of 1 to 1000 µM and the limit of detection was 51 µM. This colorimetric sensor is simple, cost-effective, and selective towards CP detection in environmental (tap water and milk) samples.