Investigation of self-immolative linkers in the design of hydrogen peroxide activated metalloprotein inhibitors

Abstract

A series of self-immolative boronic ester protected methyl salicylates and metal-binding groups with various linking strategies have been investigated for their use in the design of matrix metalloproteinase proinhibitors.

Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death

“…Aryl boronate has been known to rapidly and selectively react with H 2 O 2 to generate QM, which alkylates antioxidant GSH, thus inhibiting the cellular antioxidant systems and triggering cell death 7,20,28,44 . It has been well accepted that the intracellular level of GSH is about o10 mM (refs 20,45,46).…”

Reactive Oxygen Species-Activated Nanomaterials as Theranostic Agents

“…Boronic esters were used to hide the active site of drug molecules until they reach ROS-rich environment, where boronic esters would degrade to reveal the active site of drug molecule [83]. This concept was applied to conjugate anticancer drugs and imaging agents to boronic esters, where cleavages of boronic esters occur specifically in ROS-rich environment.…”

A prochelator with a modular masking group featuring hydrogen peroxide activation with concurrent fluorescent reporting

“…This rate constant is consistent with those observed for other compounds protected with benzyl ether-linked boronic esters. 10–11 We conclude from this observation that the inclusion of the pro-coumarin cinnamate moiety does not alter 8HQ release kinetics in this system.…”

“…The lability of the pinacol ester in HPLC conditions has been previously reported. 11 After 10 min of reaction, very little BCQ remains, but new peaks appear at 2.0 and 8.6 min with respective mass-to-charge ( m / z ) signals of 146 and 163 and absorption profiles best visualized at 254 and 330 nm, respectively (Figure 1a). These data match authentic 8HQ and Umb samples run under identical conditions (Figure 1b).…”