Expanding the Functions of KHSRP Protein: Insights into DNA G-Quadruplex Binding.

KHSRP (KH-type splicing regulatory protein) is a multifunctional nucleic acid-binding protein that regulates various cellular processes, with critical roles in controlling gene expression. G-quadruplexes (G4s) are noncanonical nucleic acid structures involved in essential cellular activities, including gene expression, and are recognized as potential therapeutic targets in cancer. The biological functions of G4s are mediated by proteins making their formation highly dynamic within cells.

Design, Synthesis, and Anticancer Activity of Drug-like Iron Chelators/G-Quadruplex Binders as Synergic Dual Targeting Agents.

Iron homeostasis is strictly related to numerous physiological pathways including cell cycle progression and cell growth. The newest anticancer strategies focus on either depleting the cells with a suitable chelator or increasing their loading by administering iron complexes to induce ferroptosis. Iron depletion inhibits cell proliferation, while iron overload induces the damage of guanine nucleobases in G-quadruplex structures via ROS generation, leading to genome instability.

Screening of native wild Salvia nemorosa populations for chemical compositions, antioxidant activity and UHPLC-HRMS profiling.

In this study, screening of the collected 70 Salvia nemorosa L. populations from 54 habitats from West Azerbaijan province, Iran was evaluated by analyzing the content of phytochemical compounds, antioxidant activity, and UHPLC-HRMS profiling in different populations. The aerial parts of the plants were analyzed based on total phenolic (TPC) and flavonoid (TFC), total tannin (TTC), ascorbic acid (AAC), chlorophylls (Cla, and Clb), total carotenoid (TCC), β-carotene, antioxidant activity (by DPPH and FRAP assays), and 40 polyphenolic compounds by UHPLC-HRMS (phenolic acids, flavonoids and fatty acyl glicosides).

Pursuing Polypharmacology: Benzothiopyranoindoles as G-Quadruplex Stabilizers and Topoisomerase I Inhibitors for Effective Anticancer Strategies.

Here, we explored the benzothiopyranoindole scaffold to develop antiproliferative agents with a polypharmacological profile targeting both G-quadruplex (G4)-structures and Topoisomerase (Topo) I enzyme. In a preliminary optimization phase, compound was selected from an in-house collection as a suitable lead for the rational development of a small library of analogs (-). When assayed in NIH's NCI-60 Human Cancer Cell Line In Vitro Screen Program, compound and its demethylated analogue showed significant antiproliferative/cytotoxic activity.

Sensitization of melanoma cells to standard chemotherapy: G-quadruplex binders as synergistic agents.

The use of chemotherapeutics has achieved considerable success in cancer therapy; however, their toxicity can severely impact patients' health. In this study, aiming to reduce the doses and potential side effects of traditional chemotherapeutics, we systematically treated A375MM human melanoma cells with seven clinically approved antineoplastic drugs, in combination with three well-characterized G-quadruplex (G4) ligands, using either simultaneous or sequential dosing schedules. Interestingly, the G4 binders synergized with most of the investigated anticancer drugs, with the degree of synergism being strictly dependent on both the treatment schedule and the drug sequence employed.