Dataset Information

Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity.

ABSTRACT: We report here the synthesis of novel thymine biomimetic photo-adducts bearing an alkane spacer between nucleobases and characterized by antimelanoma activity against two mutated cancer cell lines overexpressing human Topoisomerase 1 (TOP1), namely SKMEL28 and RPMI7951. Among them, Dewar Valence photo-adducts showed a selectivity index higher than the corresponding pyrimidine-(6-4)-pyrimidone and cyclobutane counterpart and were characterized by the highest affinity towards TOP1/DNA complex as evaluated by molecular docking analysis. The antimelanoma activity of novel photo-adducts was retained after loading into UV photo-protective lignin nanoparticles as stabilizing agent and efficient drug delivery system. Overall, these results support a combined antimelanoma and UV sunscreen strategy involving the use of photo-protective lignin nanoparticles for the controlled release of thymine dimers on the skin followed by their sacrificial transformation into photo-adducts and successive inhibition of melanoma and alert of cellular UV machinery repair pathways.

SUBMITTER: Gabellone S

PROVIDER: S-EPMC8777952 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity.

Gabellone Sofia S Piccinino Davide D Filippi Silvia S Castrignanò Tiziana T Zippilli Claudio C Del Buono Davide D Saladino Raffaele R

International journal of molecular sciences 20220114 2

We report here the synthesis of novel thymine biomimetic photo-adducts bearing an alkane spacer between nucleobases and characterized by antimelanoma activity against two mutated cancer cell lines overexpressing human Topoisomerase 1 (TOP1), namely SKMEL28 and RPMI7951. Among them, Dewar Valence photo-adducts showed a selectivity index higher than the corresponding pyrimidine-(6-4)-pyrimidone and cyclobutane counterpart and were characterized by the highest affinity towards TOP1/DNA complex as e ...[more]

PMID: 35055101

Similar Datasets

Project description:Silver nanoparticles (AgNPs) are excellent antimicrobial agents and promising candidates for preventing or treating bacterial infections caused by antibiotic resistant strains. However, their increasing use in commercial products raises concerns about their environmental impact. In addition, traditional physicochemical approaches often involve harmful agents and excessive energy consumption, resulting in AgNPs with short-term colloidal stability and silver ion leaching. To address these issues, we designed stable hybrid lignin-silver nanoparticles (AgLigNPs) intended to effectively hit bacterial envelopes as a main antimicrobial target. The lignin nanoparticles (LigNPs), serving as a reducing and stabilizing agent for AgNPs, have a median size of 256 nm and a circularity of 0.985. These LigNPs were prepared using the dialysis solvent exchange method, producing spherical particles stable under alkaline conditions and featuring reducing groups oriented toward a wrinkled surface, facilitating AgNPs synthesis and attachment. Maximum accumulation of silver on the LigNP surface was observed at a mass reaction ratio mAg:mLig of 0.25, at pH 11. The AgLigNPs completely inhibited suspension growth and reduced biofilm development by 50% in three tested strains of Pseudomonas aeruginosa at a concentration of 80/9.5 (lignin/silver) mg L-1. Compared to unattached AgNPs, AgLigNPs required two to eight times lower silver concentrations to achieve complete inhibition. Additionally, our silver-containing nanosystems were effective against bacteria at safe concentrations in HEK-293 and HaCaT tissue cultures. Stability experiments revealed that the nanosystems tend to aggregate in media used for bacterial cell cultures but remain stable in media used for tissue cultures. In all tested media, the nanoparticles retained their integrity, and the presence of lignin facilitated the prevention of silver ions from leaching. Overall, our data demonstrate the suitability of AgLigNPs for further valorization in the biomedical sector.

Project description:The prevalence and severity of skin cancer, specifically malignant melanoma, among Caucasians remains a significant concern. Natural compounds from plants have long been explored as potential anticancer agents. Betulinic acid (BI) has shown promise in its therapeutic properties, including its anticancer effects. However, its limited bioavailability has hindered its medicinal applications. To address this issue, two recently synthesized semisynthetic derivatives, N-(2,3-indolo-betulinoyl)diglycylglycine (BA1) and N-(2,3-indolo-betulinoyl)glycylglycine (BA2), were compared with previously reported compounds N-(2,3-indolo-betulinoyl)glycine (BA3), 2,3-indolo-betulinic acid (BA4), and BI. These compounds were evaluated for their effects on murine melanoma cells (B164A5) using various in vitro assays. The introduction of an indole framework at the C2 position of BI resulted in an increased cytotoxicity. Furthermore, the cytotoxicity of compound BA4 was enhanced by conjugating its carboxylic group with an amino acid residue. BA2 and BA3, with glycine and glycylglycine residues at C28, exhibited approximately 2.20-fold higher inhibitory activity compared to BA4. The safety assessment of the compounds on human keratinocytes (HaCaT) has revealed that concentrations up to 10 µM slightly reduced cell viability, while concentrations of 75 µM resulted in lower cell viability rates. LDH leakage assays confirmed cell membrane damage in B164A5 cells when exposed to the tested compounds. BA2 and BA3 exhibited the highest LDH release, indicating their strong cytotoxicity. The NR assay revealed dose-dependent lysosome disruption for BI and 2,3-indolo-betulinic acid derivatives, with BA1, BA2, and BA3 showing the most cytotoxic effects. Scratch assays demonstrated concentration-dependent inhibition of cell migration, with BA2 and BA3 being the most effective. Hoechst 3342 staining revealed that BA2 induced apoptosis, while BA3 induced necrosis at lower concentrations, confirming their anti-melanoma properties. In conclusion, the semisynthetic derivatives of BI, particularly BA2 and BA3, show promise as potential candidates for further research in developing effective anti-cancer therapies.

Dataset Information

Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity.

Publications

Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets