Design, synthesis, and evaluation of cyclic C7-bridged monocarbonyl curcumin analogs containing an o -methoxy phenyl group as potential agents against gastric cancer.

Autor: Gan X; The Second Affiliated Hospital and Yuying Children's Hospital of the Wenzhou Medical University, Wenzhou, China.; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, China.; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China., Wu Y; The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, China., Zhu M; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China., Liu B; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Kong M; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Xi Z; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Li K; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Wang H; Municipal Hospital Affiliated to Taizhou University, Taizhou, China., Su T; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China., Yao J; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China., Khushafah F; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China., Yi B; The Second Affiliated Hospital and Yuying Children's Hospital of the Wenzhou Medical University, Wenzhou, China., Wang J; Municipal Hospital Affiliated to Taizhou University, Taizhou, China., Li W; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Wu J; The Second Affiliated Hospital and Yuying Children's Hospital of the Wenzhou Medical University, Wenzhou, China.; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, China.; The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, China.
Jazyk: angličtina
Zdroj: Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2024 Dec; Vol. 39 (1), pp. 2314233. Date of Electronic Publication: 2024 Feb 22.
DOI: 10.1080/14756366.2024.2314233
Abstrakt: The structure-activity relationship (SAR) between toxicity and the types of linking ketones of C7 bridged monocarbonyl curcumin analogs (MCAs) was not clear yet. In the pursuit of effective and less cytotoxic chemotherapeutics, we conducted a SAR analysis using various diketene skeletons of C7-bridged MCAs, synthesized cyclic C7-bridged MCAs containing the identified low-toxicity cyclopentanone scaffold and an o -methoxy phenyl group, and assessed their anti-gastric cancer activity and safety profile. Most compounds exhibited potent cytotoxic activities against gastric cancer cells. We developed a quantitative structure-activity relationship model ( R 2 > 0.82) by random Forest method, providing important information for optimizing structure. An optimized compound 2 exhibited in vitro and in vivo anti-gastric cancer activity partly through inhibiting the AKT and STAT3 pathways, and displayed a favorable in vivo safety profile. In summary, this paper provided a promising class of MCAs and a potential compound for the development of chemotherapeutic drugs.
Databáze: MEDLINE