Column Chromatography-Free Synthesis of Spirooxindole and Spiroindanone-Based Naphthalimides as Potent c-MYC G4 Stabilizers and HSA Binders for Elevating Anticancer Potential

ACS Applied Bio Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

G-quadruplex (G4) DNA plays a pivotal regulatory role in fundamental biological processes, integral for governing cellular functions such as replication, transcription, and repair living cells. Within cancer cells, G4 exerts an impact on the expression of crucial genes c-MYC, effectively repressing its activity when structured within promoter region. Therefore, employing molecular scaffolds to target these structures offers attractive strategy altering their functions. In our pursuit potent selective binders, herein we report series spironaphthalimide–pyrrolidine analogues that demonstrate ability stabilize c-MYC formation subsequently inhibit expression. These are evaluated anticancer against 60 human cell lines at 10 μM. The most 8j 21c underwent additional testing five dose concentrations (10–4–10–8 M) where low MG-MID GI50 values observed both (9.98 μM) (2.49 μM). To correlate with antiproliferative activity, mechanism is explored vitro by performing Pu27 binding studies through multispectroscopic techniques, results compared Pu22, telomere, calf thymus DNA. Additionally, insights from docking suggested stacking over G-tetrad analogues, quantum mechanical further reinforcing rationale stability this quadruplex secondary structure. also affinity serum albumin, revealing robust capability bind potentially facilitate targeted delivery specific sites. Amidst abundance G4s across genome, above findings underscore significance spiro multitargeting attributes, marking transformative leap forward G4-ligand innovation, promising frontiers quest effective modalities.

Язык: Английский

Current developments in PI3K-based anticancer agents: Designing strategies, biological activity, selectivity, structure-activity correlation, and docking insight

Bioorganic Chemistry, Год журнала: 2024, Номер 154, С. 108011 - 108011

Опубликована: Ноя. 29, 2024

Язык: Английский