Dibenzothiophene-S-oxide Derivatives for Targeted Atomic Oxygen Release
Solution Overview
Problem
Current methods for generating reactive oxygen species like atomic oxygen (O(3P)) in solution are challenging due to high energy requirements, and existing dibenzothiophene-S-oxide (DBTO) derivatives face limitations in cell penetration and intracellular targeting, which hampers their effectiveness as anti-cancer agents.
Innovation Solution
The use of specific water-soluble DBTO derivatives, such as 5-oxo-2,8-diacetoxymethyldibenzothiophene, which release O(3P) upon UV-A light exposure, are administered to cancer cells, inducing apoptosis through increased oxidative stress.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high energy methods are used to generate atomic oxygen in solution, then atomic oxygen can be produced, but the energy requirements become prohibitively high
Solution Approach 1:
The patent applies preliminary action by incorporating atomic oxygen precursor groups directly into the dibenzothiophene-S-oxide molecular structure during compound synthesis. This allows atomic oxygen to be generated in situ within cells through UV-A irradiation, eliminating the need for high-energy external generation methods and enabling targeted delivery to cancer cells
Solution Approach 2:
The patent uses dibenzothiophene-S-oxide derivatives as intermediary compounds that contain latent atomic oxygen precursors. These compounds serve as stable carriers that can be administered systemically and then activated locally by UV-A light to release atomic oxygen, bridging the gap between stable storage and reactive function
2Quantity of substance
If existing DBTO derivatives are used, then they can serve as O(3P) precursors, but their cell penetration and intracellular targeting are insufficient
Solution Approach 1:
The patent applies local quality by designing compounds with specific functional groups (carboxylic acid, hydroxyl, amino groups) that enable selective interaction with cellular components. These localized functional modifications enhance water solubility, cell membrane penetration, and mitochondrial targeting without altering the core O(3P) precursor functionality
Solution Approach 2:
The patent creates composite molecular structures by combining the dibenzothiophene-S-oxide core with various functional moieties (sulfonic acid groups, carboxylic acid groups, amino groups, sugar moieties). This composite approach integrates multiple functions: O(3P) generation, water solubility, cell penetration, and intracellular targeting into a single molecule
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The described compounds effectively decrease cancer cell viability by producing atomic oxygen upon UV-A irradiation, demonstrating enhanced cell penetration and intracellular targeting, thereby inducing apoptosis in cancer cells.
Implementation Method 1
exposing a cancer cell in said patient to UV-A light
Implementation Method 2
Dibenzothiophene-S-oxide (DBTO) has been suggested to be an O(3P) pre-cursor in condensed phase
Data Source
AI summary
In one aspect, the present disclosure provides a compound of the formula: (I) wherein the variables are as defined herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein.