Harnessing the Sulfur-for-Oxygen Shift: A Magic Bullet for Dynamic Photophysical and Anticancer Activities of Indole-Barbituric Acid Construct.

The development of small molecule-based drugs emerged as a cornerstone of modern drug discovery. Structural activity relationship (SAR) studies in medicinal chemistry are crucial for lead optimization, where a subtle change in the substituent can significantly alter its binding affinity with the biological target. Herein, a highly efficient single-atom substitution (SAS) approach has been developed, where sulfur for oxygen strategy is utilized as a powerful molecular editing technique to identify N-vinyl Indole-thiobarbituric acid (6a) as a novel small molecule-based scaffold with tunable photophysical and antiproliferative activities.

Atomically precise copper nanoclusters mediated Fenton-like reaction for cancer chemodynamic therapy.

We developed stable luminescent morpholine-appended copper nanoclusters CuNCs@MorMB with an ultra-small size (<3 nm) and a long emission lifetime (577 ns). They mediate a Fenton-like reaction to produce reactive hydroxyl radicals (˙OH), subsequently depleting antioxidant glutathione levels for cancer chemodynamic therapy (CDT).

Alkaline phosphatase (ALP) activatable small molecule-based prodrugs for cancer theranostics.

Highly water-soluble small molecule-based prodrugs (5-FUPD and SAHAPD) are formulated. They comprise a phosphate group to lock the active drug payload (5-fluorouracil and SAHA) along with a turn-on fluorophore consisting of a glutathione (GSH) depletory feature. Installation of the phosphate group along with purification of final product has been accomplished in an operationally facile manner.