Rammohan College

Two novel metal complexes-Ni(II) (1) and Cu(II) (2)-bearing the same Schiff base ligand were synthesised and characterised using regular spectroscopic methods and single-crystal X-ray diffraction. Both complexes were stable for experimental duration, as assessed through UV-Vis and HPLC-MS methods. Their antioxidant and tyrosinase inhibitory activities were determined spectrophotometrically, revealing dose-dependent responses. SAR revealed that the presence of free aromatic -OH groups in the complexes favours the hydrogen atom transfer (HAT) process as the most probable mechanism for radical neutralisation, and aids in mimicking L-tyrosine for competitive inhibition of tyrosinase. 1 and 2 showed DNA interaction ability with CT-DNA through absorption and emission titrations, along with circular dichroism measurements. Molecular docking revealed that 1 fully intercalates between DNA base pairs, whereas 2 exhibits a combination of intercalation and minor groove binding. Both 1 and 2 were cytotoxic to B16F10 murine melanoma cells, with IC50 values of 3.117 +/- 1.28 mu M and 0.576 +/- 0.09 mu M, respectively, as measured by the MTT assay. They significantly suppressed cellular proliferation and ROS production, as shown by colony formation and DCFDA assays, respectively. Moreover, both reduced intracellular melanin levels and induced G1 phase arrest, DNA fragmentation, and apoptosis, highlighting their potential as melanogenesis-targeted therapeutics.

Breast cancer remains a leading cause of cancer-related mortality in women globally. Approved chemotherapeutics, while effective, are associated with severe side effects, necessitating the development of safer, more targeted treatments. Our present study investigated the therapeutic potential of a thiazole-based hydroxamic acid derivative, 1, against MCF-7 breast cancer cells. 1 exhibited potent cytotoxicity with an IC50 of 21.18 ± 2.01 μM, comparable to the cytotoxicity of doxorubicin IC50 of 18.08 ± 1.20 μM, yet demonstrated excellent selectivity with no significant cytotoxicity towards normal MCF-10A epithelial cells (62.37 ± 1.01 μM). Swiss ADME analysis confirmed its favourable drug-likeness and non-PgP substrate status. Flow cytometric analysis confirmed that 1 demonstrated substantial apoptotic cell death, inducing 45 % apoptosis compared to 2.62 % in the control group, by 75.8 % mitochondrial membrane depolarization and S-phase cell cycle arrest (with cell accumulation reaching 30.1 % at 24 h). Spectroscopic and computational studies inferred the minor-groove binding ability of 1 towards CT-DNA. Immunoblotting confirmed the DNA damage response (upregulation of γH2AX and p-ATM expression) which activated the intrinsic apoptotic pathway (upregulation of p53 and Bax/Bcl-2 ratio from 1.1 in control to 4 following treatment and cleaved caspase-7). The induction of DNA damage was also visualized by increase in the comet tail moment (1 induced a tail moment of 54.75 ± 1.50 vs. 11.79 ± 2.23 for control). Subacute toxicity in BALB/c mice confirmed 1's safety, with no adverse liver, renal, biochemical or hematological effects up to 10 mg/kg. Collectively, the findings identify 1's potential as a chemotherapeutic lead agent for breast cancer.

Herein, we introduce a visible-light-induced copper-catalyzed decarboxylative C(sp3)-C(sp3) cross-coupling of α,β-unsaturated carboxylic acids with unactivated cyclic ethers. The protocol employs an underexplored catalytic combination of CuSO4·5H2O/sodium L-(+)-ascorbate merged with an iridium photocatalyst for enabling direct C2-selective functionalization of cyclic ethers under ambient conditions. This transformation provides modular access to 2-oxyalkylated ketones via a rare anti-Giese-type radical addition. A wide range of cinnamic acid derivatives, including electron-rich, electron-deficient, heteroaryl, and sterically hindered substrates, as well as complex bioactive and natural product-derived motifs, have been tolerated with excellent yields. Detailed mechanistic investigations support a Cu/Ir dual-catalytic pathway involving oxygen-derived radical intermediates and copper-assisted decarboxylation.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) is indispensable for viral replication and remains a validated antiviral drug target. Naturally occurring biflavonoids, particularly those with C-C and C-O-C interflavonoid linkages, have gained attention due to their structural diversity and reported antiviral potential. In this study, an integrated in silico approach was employed to investigate the inhibitory potential of representative biflavonoids against SARS-CoV-2 Mpro. A curated library of C-C- and C-O-C-linked biflavonoids was initially screened using molecular docking within the catalytic pocket of Mpro (PDB ID: 6LU7), followed by density functional theory (DFT) calculations to evaluate electronic properties and chemical reactivity. Molecular dynamics simulations (MDS) were performed to assess the structural stability of the ligand-Mpro complexes, while binding free energies were estimated using the MM/PBSA method. Principal component analysis (PCA) and free energy landscape (FEL) analyses were applied to characterize essential motions and conformational stability during the simulations. Key interactions with the catalytic dyad (His41 and Cys145) and surrounding residues, including Glu166, His163, and Gly143, were consistently observed. Comparative analyses revealed that C-C-linked biflavonoids, particularly amentoflavone and robustaflavone, exhibited more favourable binding affinities and dynamic stability than C-O-C-linked counterparts such as hinokiflavone and ochnaflavone, although both classes demonstrated inhibitory potential. Drug-likeness and pharmacokinetic properties were evaluated using ADMET predictions and Molinspiration analysis, while toxicity assessment via ProTox-3 indicated low predicted toxicity for the top-ranked compounds. Overall, these findings suggest that naturally occurring biflavonoids, C-C- and C-O-C-linked scaffolds, represent promising leads for SARS-CoV-2 Mpro inhibition and merit further experimental validation.

The incorporation of fillers into polymer matrices is a well-established strategy to enhance mechanical, electrical, and thermal properties. However, filler–matrix compatibility remains a critical factor governing overall performance, often limiting the applicability of promising filler materials. While numerous studies have investigated individual filler systems, a systematic comparative analysis of multiple fillers within an identical polymer matrix remains notably absent. In this work, a comprehensive study is presented on the incorporation of three distinct fillers-clay, multiwalled carbon nanotubes (MWCNTs), and silver nanoparticles (AgNPs) into identical polyaniline-dinonylnaphthalene disulfonic acid (PANI–DNNDSA) gel matrices synthesized under controlled conditions to ensure uniform molecular weight and processing parameters. Each composite was evaluated for its structural, electrical, and mechanical properties to elucidate filler-specific influences and compatibility with the host matrix. The findings contribute valuable insights for both academic research and industrial applications, facilitating informed filler selection for advanced polymer design.