Department of Chemistry, McGill University, 801 Sherbrooke St. W., Montreal, QC, H3A 0B8, Canada. Electronic address:
Published: August 2024
AI Article Synopsis
Article Abstract
Antiestrogen/histone deacetylase inhibitor (HDACi) hybrids were designed by merging structures of raloxifene with suberoylanilide hydroxamic acid, incorporating the HDACi unit into the phenolic ring of the antiestrogen. These hybrids were synthesized with a range of HDACi chain lengths and assessed for bifunctionality. Four hybrids, 21 (YW471), 22 (YW490), 27(YW486), and 28 (YW487) showed good potency both as antiestrogens in a BRET assay and in a fluorometric HDACi assay. The antiproliferative activity of the hybrids was demonstrated in both ER+ MCF7 and ER- MDA-MB-231 breast cancer cell lines.
Through catalyzing the transfer of methyl groups onto the guanidinium of arginine, protein arginine methyltransferase 5 (PRMT5) was essential to the cell growth of cancer cells. By utilizing a scaffold hopping strategy, a novel series of 3,4-dihydroisoquinolin-1()-one derivatives were designed and synthesized. Through a systematic SAR study, demonstrated excellent PRMT5 inhibitory activity, potent antiproliferative activity against Z-138, favorable pharmacokinetic profiles, and low hERG toxicity.
College of Chemistry and Materials Science, Zhejiang Normal University, No. 688 Yingbin Road, Jinhua, Zhejiang Province, 321004, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education, College of Pharmacy, Jinan University, No. 601 Huangpu Avenue West, Guangzhou, 510530, China. Electronic address:
Right open reading frame kinase 2 (RIOK2) is an atypical serine threonine kinase which plays an important role in regulating ribosome synthesis and cell cycle progression. RIOK2 has been implicated in multiple human cancers and is a potential target for cancer treatment. We previously reported the discovery of CQ211 as a potent and selective RIOK2 inhibitor.
Mesenchymal stem cells (MSCs), which are multipotent adult cells with many therapeutic effects, can be derived from stromal tissues. MSCs also exert immunoregulatory effects through extracellular vesicles (EVs), cell membrane structures that carry paracrine factors. It is thought that the mediators (cytokines, growth factors, etc.
Global efforts have been made to address environmental and health concerns by promoting and adopting renewable natural resources. This study investigated the role of bagasse-based wood vinegar to synthesize and stabilize silver nanoparticles. We present a simple bottom-up approach to produce silver nanoparticles using the green reducing agent.
(-)-Exiguolide is a marine macrolide natural product with potent anticancer activity. In this study, the total synthesis of exiguolide stereoisomers, (9)-exiguolide, (9,13)-exiguolide, and (9,13,19)-exiguolide, was achieved by capitalizing on our macrocyclization/transannular pyran cyclization strategy. The impact of the stereochemical permutation on the reactivity of advanced intermediates, the conformation of the macrocyclic skeleton, and the antiproliferative activity against human cancer cells were investigated in detail.
