Cancer remains a major global health challenge, and the development of new therapeutic agents is urgently needed to overcome poor selectivity and multi-drug resistance. Targeting DNA replication enzymes such as topoisomerase I (Topo I), which regulates DNA topology during replication and transcription, represents an effective chemotherapeutic strategy. This study aimed to design and synthesize new benzothiophene and benzothienopyran derivatives as potential Topo I inhibitors with additional immunomodulatory activity. Four series of derivatives including benzothiophene (2a-c) and benzo[4,5]thieno[3,2-b]pyran (3a-c, 4a-c, and 5a-c) were synthesized, characterized, and biologically evaluated. In vitro cytotoxicity screening against the NCI-60 cancer cell panel demonstrated broad and potent activity, with several compounds showing 70 to >100% growth inhibition. The most active derivatives were further assessed in a five-dose NCI assay and a DNA relaxation assay for Topo I inhibition. Compounds 2c and 5c exhibited superior Topo I inhibition (IC50=17.69±0.6μM and 18.79±0.64μM, respectively) compared with topotecan (IC50=27.27±0.93μM) and showed higher selectivity toward cancer cells over PCS-800-017 normal cells. Both compounds induced G0/G1 cell cycle arrest and apoptosis in SR leukemia cells. Notably, compound 5c activated the cGAS-STING pathway and modulated apoptosis-related markers. Molecular docking studies rationalized the superior Topo I inhibitory potential of compound 5cvia forming strong interaction with the Topo I-DNA complex. Molecular dynamics (MD) simulation studies demonstrated remarkable positional stability of compound 5c with no significant structural perturbations in the Topo I active site. Additionally, drug-likeness and pharmacokinetic properties, predicted by SwissADME, indicated that 5c complies with Lipinski's and Veber's rules of oral bioavailability showing a bioavailability score of 0.55. These findings highlight compound 5c as a promising Topo I inhibitor with mechanistically validated multimodal anticancer activity, superior inhibitory potency compared with topotecan, and enhanced selectivity toward cancer cells over normal CD8+ cells, supporting its potential for further anticancer drug development.

Licochalcone A from Ma-Xing-Shi-Gan decoction to prevent Asthma through the inhibition of ferroptosis CD4+ T Cell by GART/HSP90α signaling pathway.

Phytochemical profiling and system-level mechanistic insights into the anti-arthritic activity of Barleria cristata: Evidence from in-silico network pharmacology, molecular docking, in-vitro and in-vivo studies.

Chemo-preventive and anti-inflammatory potential of Bilvamoola [Aegle marmelos (L.) Correa] root extract and its bioactive: Chemical standardization, in-vitro and in-silico validation.

Multi-target pyrazolopyrimidine-coumarin derivatives as potent CA IX/XII and tubulin polymerization inhibitors: Design, synthesis, and biological evaluation.

One pot synthesis of pyrazolo-piperazine-quinazoline hybrids: evaluation of anticancer activity, molecular docking and ADMET studies

This study describes the fabrication and examination of binuclear copper(II) phenylacetate (PAA) complex with metronidazole (mnz), formulated as [Cu2(μ-PAA)4(mnz)2](mnz)2(H2O)2 (1). The complex was synthesized at room temperature and the product was characterized via FTIR, UV-Vis, and PXRD. The single-crystal X-ray diffraction of complex 1 reveals that it crystallizes in the triclinic space group P-1. The SCXRD illustrated that complex 1 adopts a bidentate bridging mode with an almost ideal square-pyramidal geometry (τ5 descriptor). Complex 1 is stabilized by extended hydrogen-bonding networks, as confirmed by Hirshfeld surface analysis and 2D fingerprint plots. Quantitative analysis demonstrated that H···H interactions dominate the crystal packing (49.6% in 1), indicating that van der Waals forces are the major contributors to solid-state stability. DFT calculations confirmed the structural stability and electronic features of the binuclear copper complex. FMO analysis revealed a narrow HOMO-LUMO energy gap (1.39 eV), indicating enhanced electronic responsiveness and chemical reactivity. RDG analysis indicated that molecular stability arises from a balance of coordination-driven attractive interactions, weak dispersive forces, and localized steric effects. Furthermore, docking study against the SARS-CoV-2 main protease showed favorable binding affinity (-7.97 kcal/mol), suggesting potential biological relevance of the complex as a metal-based bioactive scaffold.

Structure-guided discovery of 4-phenyl-5-p-tolyloxymethyl-4H-1,2,4-triazole thioethers as 15-lipoxygenase inhibitors using integrated in vitro, structure-activity relationship, in silico, cytotoxicity towards MCF-7 cell line, DNA docking and MD simulation methods.

Green MW/US route from lignocellulose to FDCA-based thiadiazol scaffolds: DPP-4/COX-1 inhibition and antioxidant evaluation.

Characterizing neuroma-like formation after tail docking in sheep.

Liver cancer is the most common cause of cancer death worldwide, causing about 866,136 deaths in 2022. Several studies illustrate that constitutive nuclear factor-κB (NF-κB) activity plays a central role in the hepatic neoplastic progression, and its inhibition in hepatocytes retards and reduces the development of hepatocellular carcinoma. A recent study revealed that Metformin, a hypoglycemic agent used to treat patients with type 2 diabetes mellitus (T2DM), has significantly reduced the incidence of hepatocellular carcinoma (HCC) studied in a transgenic mouse model (TG221 strain). As NF-κB plays a key role in the development of insulin resistance, intervention with Metformin could reduce the risk of neoplastic transformation of hepatocytes. To decipher the interlink between type 2 diabetes and reduced incidence of hepatic carcinoma mediated by Metformin, we performed a systems biology study and identified a hub protein playing a crucial role in the above-said mechanism. The results suggested an association between a network of proteins in the disease mechanism and Protein kinase B (AKT1), a serine-threonine-specific kinase, as a hub protein. Molecular docking and molecular dynamics simulation studies identified the specific interactions of the tested molecules with the hub protein, thereby encouraging further studies to assess protein kinase B as a novel biomarker for hepatocellular carcinoma. While the present findings provide mechanistic insights into Metformin's antitumor effects in an insilico condition, translation of these findings to preclinical systems and to human HCC requires validation in human tissues and patient cohorts.

Sepsis, a life-threatening inflammatory syndrome, is characterized by excessive cytokine production, particularly interleukin-6 (IL-6), which drives systemic inflammation and organ dysfunction. This study investigates the anti-inflammatory mechanism of Baimaside, a flavonoid compound isolated from Apocynum venetum, in lipopolysaccharide (LPS)-induced sepsis. Using bone marrow-derived macrophages (BMDMs) and a murine sepsis model, we demonstrate that Baimaside potently inhibits IL-6 transcription and secretion by disrupting the binding of NFκB1 p50 to the κB DNA element in the IL-6 promoter. Molecular docking and mutagenesis studies reveal that Baimaside binds p50 at residues Gly61, Ser63, Asn 136 etc., inducing steric hindrance that prevents p50 recruitment to the promoter. This inhibition selectively suppresses IL-6 expression while sparing other inflammatory mediators like TNF-α and IL-1β, which are regulated by classical NF-κB pathways. In vivo, Baimaside pretreatment significantly reduces LPS-induced organ injury, improves survival rates, and attenuates systemic inflammation in mice. These findings establish Baimaside as a novel therapeutic candidate for sepsis, acting through a unique mechanism targeting the p50-IL-6 axis. This study provides a mechanistic foundation for developing Baimaside into a precision medicine agent for IL-6-driven inflammatory disorders.

Halogenated Copper(II) complex of an aniline schiff base: synthesis, spectroscopic characterization, antidiabetic activity, molecular docking, and dft studies

Isolation, antibacterial evaluation, molecular docking and DFT studies of two previously unreported terpenoids from the stem bark of Croton zambesicus

Visible light photocatalytic promoted reactions: Synthesis of polyfunctionally substituted phthalazine derivatives, ADMET, molecular docking and dynamic studies

Dual-sensor potentiometric platform utilizing β-cyclodextrin ionophores and Cu-gallic MOFs for ophthalmic drugs determination in rabbit aqueous humor

The global prevalence of gout continues to rise. Baxian Huazhuo Decoction (BHD) has demonstrated significant efficacy in the clinical treatment of acute gouty arthritis (AGA); however, its mechanism of action remains unclear. This study first employed network pharmacology analysis to identify the key components, targets, and pathways of BHD against AGA. Molecular docking studies validated the binding affinity between the components of BHD and their potential targets. Ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) was utilized to identify the active components in BHD and elucidate their fragmentation pathways. Subsequently, a monosodium urate crystal-induced AGA rabbit model was established to evaluate the invivo therapeutic efficacy of BHD. The results revealed 62 predicted active components and 268 target molecules in BHD, identifying core constituents such as gentiopicroside, limonin, and indirubin, which exhibited high affinity for targets including MAPK1, PPARG, and IL-6. Invivo experiments confirmed that BHD significantly suppressed the phosphorylation of MAPK1, reduced the levels of pro-inflammatory factors such as TNF-α and IL-6, mitigated synovial damage, and inhibited the activation of the PI3K-Akt signaling pathway. This study systematically elucidates the pharmacological basis and mechanisms of action of BHD in the treatment of AGA, providing a scientific basis for its clinical application.

Syntheses, crystal structures, theoretical insights and DNA (1BNA) docking studies of 3-(3-oxo-1,3-dihydroisobenzofuran-1-yl)aminobenzoic acid and its metal complexes

Aromatase inhibitory, anti-proliferative, and apoptosis-inducing effects of naphthoquinone-triazole derivatives for potential anti-breast cancer agents: In vitro and molecular docking studies.

Quercetin targets cytochrome P450 enzyme (CYP1A2) in colorectal cancer.