Lapachone

β-lapachone (β-Lap), a topoisomerase inhibitor, is a naturally occurring ortho -naphthoquinone phytochemical and is involved in drug resistance mechanisms. Oxaliplatin (OxPt) is a commonly used chemotherapeutic drug for metastatic colorectal cancer, and OxPt-induced drug resistance remains to be solved to increase chances of successful therapy. To reveal the novel role of β-Lap associated with OxPt resistance, 5 μM OxPt-resistant HCT116 cells (HCT116-OxPt-R) were generated and characterized via hematoxylin staining, a CCK-8 assay and Western blot analysis...

In recent years, the coupling of structurally and functionally controllable polymers with biologically active peptide materials to obtain polymer-peptide hybrids with excellent properties and biocompatibility has led to important research progress in the field of polymers. In this study, a pH-responsive hyperbranched polymer hPDPA was prepared by combining atom transfer radical polymerization (ATRP) with self-condensation vinyl polymerization (SCVP) using a three-component reaction of Passerini to obtain a monomeric initiator ABMA containing functional groups...

Owing to the advantages of the in situ production of toxic agents through catalytic reactions, nanocatalytic therapy has arisen as a highly potential strategy for cancer therapeutics in recent years. However, the insufficient amount of endogenous hydrogen peroxide (H2 O2 ) in the tumor microenvironment commonly limits their catalytic efficacy. Here, we employed carbon vesicle nanoparticles (CV NPs) with high near-infrared (NIR, 808 nm) photothermal conversion efficiency as carriers. Ultrafine platinum iron alloy nanoparticles (PtFe NPs) were grown in situ on the CV NPs, where the highly porous nature of the resultant CV@PtFe NPs was employed to encapsulate a drug, β-lapachone (La), and phase-change material (PCM)...

β-Lapachone is an ortho -naphthoquinone natural product with significant antiproliferative activity but suffers from adverse systemic toxicity. The use of photoremovable protecting groups to covalently inactivate a substrate and then enable controllable release with light in a spatiotemporal manner is an attractive prodrug strategy to limit toxicity. However, visible light-activatable photocages are nearly exclusively enabled by linkages to nucleophilic functional sites such as alcohols, amines, thiols, phosphates, and sulfonates...

Leishmaniasis is a neglected disease that affects millions of people worldwide, and special attention should be given to treatment because the available drugs have limitations, which can lead to low therapeutic adherence and parasitic resistance. This study evaluated the activity of the bioactive naphthoquinones, lapachol and β-lapachone, against Leishmania amazonensis. The cell alterations were evaluated in vitro on promastigote and amastigote forms. The lethal dose (LD50) at 24, 48, and 72 h on the promastigote's forms using lapachol was 75...

Introduction: Lung cancer the most prevalent cause of cancer-related deaths, and current therapies lack sufficient specificity and efficacy. This study developed an injectable thermosensitive hydrogel harboring hollow copper sulfide nanoparticles and β-lapachone (Lap) (CLH) for lung tumor treatment. Methods: The hydrogel-encapsulated CLH system can remotely control the release of copper ions (Cu2+ ) and drugs using photothermal effects for non-invasive controlled-release drug delivery in tumor therapy...

The rapid development of nanomedicine has brought hope and confidence to the precise treatment of tumors. However, the efficacy of nanoparticle-mediated therapy is severely limited due to phagocytosis and clearance by macrophages. CD47 is a well-documented ″don't eat me″ signaling molecule that binds to the SIRPα receptor on the macrophage surface, inhibiting the phagocytic behavior of the macrophages. In this study, CD47-overexpressing cancer cell membranes were used to coat hollow copper sulfide nanoparticles...

The ability to control the activation of prodrugs by transition metals has been shown to have great potential for controlled drug release in cancer cells. However, the strategies developed so far promote the cleavage of C-O or C-N bonds, which limits the scope of drugs to only those that present amino or hydroxyl groups. Here, we report the decaging of an ortho -quinone prodrug, a propargylated β-lapachone derivative, through a palladium-mediated C-C bond cleavage. The reaction's kinetic and mechanistic behavior was studied under biological conditions along with computer modeling...

Chemodynamic therapy (CDT) relies on the tumor microenvironment (e.g., high H2 O2 level) responsive Fenton-like reactions to produce hydroxyl radicals (·OH) against tumors. However, endogenous H2 O2 is insufficient for effective chemodynamic responses. An NAD(P)H: quinone oxidoreductase 1 (NQO1)high catalase (CAT)low therapeutic window for the use of NQO1 bioactive drug β-lapachone (β-Lap) is first identified in endometrial cancer (EC). Accompanied by NADH depletion, NQO1 catalyzes β-Lap to produce excess H2 O2 and initiate oxidative stress, which selectively suppress NQO1high EC cell proliferation, induce DNA double-strand breaks, and promote apoptosis...

Chemotherapy remains the mainstay of cancer treatment, and doxorubicin (DOX) is recommended as a first-line chemotherapy drug against cancer. However, systemic adverse drug reactions and multidrug resistance limit its clinical applications. Here, a tumor-specific reactive oxygen species (ROS) self-supply enhanced cascade responsive prodrug activation nanosystem (denoted as PPHI@B/L) was developed to optimize multidrug resistance tumor chemotherapy efficacy while minimizing the side effects. PPHI@B/L was constructed by encapsulating the ROS-generating agent β-lapachone (Lap) and the ROS-responsive doxorubicin prodrug (BDOX) in acidic pH-sensitive heterogeneous nanomicelles...

In this work, the synthesis, characterization and photophysical assays of a new trans -A2 B-corrole derivative from the naturally occurring quinone are described. β-Lapachone is a naturally occurring quinoidal compound that provides highly fluorescent heterocyclic compounds such as lapimidazoles. The new trans -A2 B-corrole compound was obtained from the reaction between 2,3,4,5,6-(pentafluorophenyl)dipyrromethane and the lapimidazole bearing an aldehyde group. The dyad was characterized by high-resolution mass spectrometry (HRMS), NMR spectroscopy (1 H, COSY 2D, HMBC, 19 F), FT-IR, UV-vis, steady-state and time-resolved fluorescence, electrochemical studies (CV), TD-DFT analysis and photobiological experiments, in which includes aggregation, stability in solution, photostability and partition coefficients assays...

Immunotherapies comprising programmed cell death protein 1/PD ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors are effective cancer treatments. However, the low response rate and immunoresistance resulting from alternative immune checkpoint upregulation and inefficient immune stimulation by T cells are problematic. The present report describes a biomimetic nanoplatform that simultaneously blocks the alternative T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) checkpoint and activates the stimulator of interferon genes (STING) signaling pathway in situ for enhanced antitumor immunity...

Theranostics combines therapeutic and imaging diagnostic techniques that are extremely dependent on the action of imaging agent, transporter of therapeutic molecules, and specific target ligand, in which fluorescent probes can act as diagnostic agents. In particular, naphthoimidazoles are potential bioactive heterocycle compounds to be used in several biomedical applications. With this aim, a group of seven naphth[1,2- d ]imidazole compounds were synthesized from β-lapachone. Their optical properties and their cytotoxic activity against cancer cells and their compounds were evaluated and confirmed promising values for molar absorptivity coefficients (on the order of 103 to 104 ), intense fluorescence emissions in the blue region, and large Stokes shifts (20-103 nm)...

Head and neck squamous cell carcinoma (HNSCC) cells are highly heterogeneous in their metabolism and typically experience elevated reactive oxygen species (ROS) levels such as superoxide and hydrogen peroxide (H2 O2 ) in the tumor microenvironment. Tumor cells survive under these chronic oxidative conditions by upregulating antioxidant systems. To investigate the heterogeneity of cellular responses to chemotherapeutic H2 O2 generation in tumor and healthy tissue, we leveraged single-cell RNA-sequencing (scRNA-seq) data to perform redox systems-level simulations of quinone-cycling β-lapachone treatment as a source of NQO1-dependent rapid superoxide and hydrogen peroxide (H2 O2 ) production...

BACKGROUND: Bacterial infections constantly have a large impact on public health, because of increased rates of resistance and reduced frequency of development of novel antibiotics. The utility of conventional antibiotics for treating bacterial infections has become increasingly challenging. The aim of the study was to assess the antibacterial effect of β-Lapachone (β-Lap), a novel synthetic compound. METHODS: The antibacterial activity of the β-Lap compound was examined against laboratory strains by agar well diffusion method and broth dilution assay...

Nanotechnology shows the power to improve efficacy and reduce the adverse effects of anticancer agents. As a quinone-containing compound, beta-lapachone (LAP) is widely employed for targeted anticancer therapy under hypoxia. The principal mechanism of LAP-mediated cytotoxicity is believed due to the continuous generation of reactive oxygen species with the aid of NAD(P)H: quinone oxidoreductase 1 (NQO1). The cancer selectivity of LAP relies on the difference between NQO1 expression in tumors and that in healthy organs...

By analyzing the crystal structure of NQO1, an additional binding region for the ligand was discovered. In this study, a series of derivatives with a novel skeleton bearing two nitrogen redox centers were designed by introducing amines or hydrazines to fit with the novel binding region of NQO1. Compound 24 with a (4-fluorophenyl)hydrazine substituent was identified as the most efficient substrate for NQO1 with the reduction rate and catalytic efficiency of 1972 ± 82 μmol NADPH/min/μmol NQO1 and 6...

BACKGROUND: Nicotinamide adenine dinucleotide (NAD+ ) metabolism is involved in the entire physiopathological process and is critical to human health. Long-term imbalance in NAD+ homeostasis is associated with various diseases, including non-alcoholic fatty liver disease, diabetes mellitus, cardiovascular diseases, neurodegenerative disorders, aging, and cancer, making it a potential target for effective therapeutic strategies. Currently, several natural products that target NAD+ metabolism have been widely reported to have significant therapeutic effects, but systematic summaries are lacking...

Epoxy-α-lapachone (ELAP), an oxirane-functionalized molecule synthesized from naturally occurring lapachol, has shown promising activity against murine infection with Leishmania (Leishmania) amazonensis. Herein, we report the successful development of microemulsions (ME) loaded with ELAP (ELAP-ME) using Capmul MCM, Labrasol, and PEG 400. Stability studies revealed that ELAP-ME (100 µg/mL of ELAP), which was comprised of particles smaller than 120.4 ± 7.7 nm, displayed a good stability profile over 73 days...

The emerging tumor ferroptosis therapy confronts impediments of the tumor microenvironment (TME) with weak intrinsic acidity, inadequate endogenous H2 O2 , and a powerful intracellular redox balance system that eliminates toxic reactive oxygen species (ROS). In this study, w e propose a strategy of Fenton reaction cycloacceleration initiated by remodeling the TME for magnetic resonance imaging (MRI)-guided high performance ferroptosis therapy of tumors. The synthesized nanocomplex (named as CON3-LAP-HMON@GF7-ABS-PEG) exhibits enhanced accumulation at carbonic anhydrase IX (CAIX)-positive tumors based on the CAIX-mediated active targeting, and increased acidification via the inhibition of CAIX by 4-(2-aminoethyl) benzene sulfonamide (ABS) (i...