Year: 2025
Type: article
Abstract: ABSTRACT Photopharmacology offers a novel approach to eliminate side effects of chemotherapy treatment via site‐specific activation of light‐active anticancer agents, which are typically constructed by the installation of light‐cleavable or light‐switchable molecules onto known drugs or inhibitors. The light‐switchable drugs being able to reversibly control biological activities are more advantageous, but the design of such compounds is very challenging. We synthesized a small series of photoswitchable S‐arylsulfonylurea‐based EP4 antagonists by substituting a core structural unit of a potent EP4 antagonist, grapiprant. In vitro cell‐based EP4 activity studies revealed that all light‐induced cis isomers of these compounds are more potent than their trans isomers. Compound 3 , with an azopyrazole photoswitch and a para ‐methyl substitution in the S ‐phenyl ring, displayed the highest EP4 antagonism by its cis isomer and a considerably larger activity difference (ca. 1.8‐fold) between trans and cis photoisomers. It showed (near) complete photoisomerization (∼95%–98%) upon 365 nm (forward) and 520 nm (reverse) light irradiations. The metastable cis isomers demonstrated high thermal stability (t 1/2 = 1–3 days). All compounds were resistant to photobleaching and showed impressive stability for reduction with glutathione (10 mM). This study constitutes a proof‐of‐concept to design photoswitchable EP4 antagonists, and the structure‐activity relationship revealed herein may help design more potent grapiprant derivatives.
Source: Chemistry - A European Journal
Authors: Md. Akram Ali, Satyajit Bera, Rajib Chakraborty, Susanta Kumar Mondal, Supriya Bhunia, Tapas Sardar, Sabyasachi Chakraborty, Subhas Samanta
Institutions: University of Calcutta, TCG Lifesciences (India)
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: bronze
Award: G255210996
OpenAlex ID: W7117571252