Type 1 Phototherapeutic Agents, Part I: Preparation and Cancer Cell Viability Studies of Novel Photolabile Sulfenamides

Abstract

Novel type 1 phototherapeutic agents based on compounds containing S–N bonds (sulfenamides) were synthesized, assessed for free radical generation, and evaluated in vitro for cell death efficacy in four cancer cell lines (U937, HTC11, KB, and HT29). All of the compounds were found to produce copious free radicals upon photoexcitation with UV-A and/or UV-B light, as determined by electron spin resonance spectroscopy. Among the sulfenamides, the most potent compounds were derived from dibenzazepine 7b and dihydroacridine 8b as determined in all of the four cancer cell lines.

Novel Pulsed Electron Paramagnetic Resonance Techniques for the Studies of Structure and Dynamics of Photo‐excited Triplet State of Organic Molecules: A Professional Journey

“…A review article summarizing these studies was published in Nano Today . We further applied EPR techniques to study the therapeutic efficacy of some photo‐therapeutic agents . We also investigated the cytotoxicity of ZnO nanoparticles in my laboratory at WUSTL …”

Free‐Amine‐Directed Alkenylation of C(sp2)H and Cycloamination by Palladium Catalysis

“…[24] In addition, compounds containing a fused, seven-membered central ring are potent phototherapeutic agents. [25] We tested the generality of this protocol by applying it to the synthesis of diverse tricyclic compounds with a sevenmembered amine ring (Table 3). Electron-rich arenes showed a better reactivity than electron-deficient arenes (products 7 d, 7 e, and 7 g) and delivered the desired products in moderate yields (7 a-c and 7 f; for X-ray crystallography of 7 b, see the Supporting Information).…”

“…This kind of tricyclic amine core is an important substructure unit of arginine vasopressin antagonists, and has a substantial effect on their antagonistic activity for the V 1a and V 2 receptors 24. In addition, compounds containing a fused, seven‐membered central ring are potent phototherapeutic agents 25…”

Insight Into the Inhibition of Ribonucleotide Reductases by 2'-chloro-2'-deoxynucleotides and 2'-azido-2'-deoxynucleotides: Biomimetic Studies with Model Substrates

“…113,117 Sulfenamides are photolabile compounds classified as type-1 phototherapeutic agents. 117 They are reported to generate abundant free radicals upon photoexcitation with UV/Visible light. These photolyzed compounds cause cell death in a dose dependent manner.…”

“…Phototherapeutic agents are classified into two broad categories type-1 and type-2. 117 In type-1, absorption of light by the photosensitizer causes bond fragmentation to produce reactive intermediates such as free radicals, which induces cell death. Type-2 processes induce cell death by generation of reactive oxygen species (ROS) like hydroxyl radical, superoxide radical anion.…”