7pnl

Complex between monomolecular human telomeric G-quadruplex and a sulfonamide derivative of the natural alkaloid Berberine

spinqualitylabelsall models 7pnl, resolution 1.83Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7pnl is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.83Å Ligands: 7VE, K Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed A novel class of compounds designed to hit two anti-tumour targets, G-quadruplex structures and human carbonic anhydrases (hCAs) IX and XII is proposed. The induction/stabilisation of G-quadruplex structures by small molecules has emerged as an anticancer strategy, disrupting telomere maintenance and reducing oncogene expression. hCAs IX and XII are well-established anti-tumour targets, upregulated in many hypoxic tumours and contributing to metastasis. The ligands reported feature a berberine G-quadruplex stabiliser scaffold connected to a moiety inhibiting hCAs IX and XII. In vitro experiments showed that our compounds selectively stabilise G-quadruplex structures and inhibit hCAs IX and XII. The crystal structure of a telomeric G-quadruplex in complex with one of these ligands was obtained, shedding light on the ligand/target interaction mode. The most promising ligands showed significant cytotoxicity against CA IX-positive HeLa cancer cells in hypoxia, and the ability to stabilise G-quadruplexes within tumour cells. Development of a multi-targeted chemotherapeutic approach based on G-quadruplex stabilisation and carbonic anhydrase inhibition.,Nocentini A, Di Porzio A, Bonardi A, Bazzicalupi C, Petreni A, Biver T, Bua S, Marzano S, Amato J, Pagano B, Iaccarino N, De Tito S, Amente S, Supuran CT, Randazzo A, Gratteri P J Enzyme Inhib Med Chem. 2024 Dec;39(1):2366236. doi: , 10.1080/14756366.2024.2366236. Epub 2024 Jun 18. PMID:38905127 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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