Cholecystokinin-1 receptor antagonists: 5-hydroxy-5-aryl-pyrrol-2-ones as anticancer agents??
MedChemComm Pub Date: 2016-04-01 DOI: 10.1039/C6MD00052E
Abstract
A new class of 5-arylated 5-hydroxypyrrolones was derived from mucochloric acid in 2 synthetic steps and the chemical structure was confirmed additionally by X-ray analysis. Using a radiolabelled binding assay, potent CCK1 selective ligands were identified (CCK1: 12 nM) and the antagonism was confirmed by using isolated tissue preparations. A series of isobutyl derivatives displayed unsurmountable CCK antagonistic properties and in vitro excellent inhibition of proliferation was obtained in cholecystokinin related cancer cell lines in the nanomolar range. Finally, using xenograft studies in nude mice, two selected pyrrolone derivatives, X = H and X = F a fluorinated analogue (PNB-028 ), showed a strong inhibition of tumour growth in a chemo-resistant colon cancer-(MAC 16) and a human pancreatic cell line (MIAPACA) at 50 mg kg?1 by oral administration.
Recommended Literature
- [1] Establishing the accuracy of position-specific carbon isotope analysis of propane by GC-pyrolysis-GC-IRMS ChangjieLiu,PengLiu,XiaofengWang,XiaoqiangLi,JuskeHorita 10.1002/rcm.9494
- [2] Enabling non-flammable Li-metal batteries via electrolyte functionalization and interface engineering? Jing Yu,Yu-Qi Lyu,Jiapeng Liu,Mohammed B. Effat,Junxiong WuJ. Mater. Chem. A, 2019,7, 17995-18002 10.1039/C9TA03784E
- [3] Excitation energies from ground-state density-functionals by means of generator coordinates A. B. F. da Silva,K. CapellePhys. Chem. Chem. Phys., 2009,11, 4564-4569 10.1039/B902529D
- [4] Evolution in surface coverage of CH3NH3PbI3?XClXvia heat assisted solvent vapour treatment and their effects on photovoltaic performance of devices Dhirendra K. Chaudhary,Pramendra Kumar,Lokendra KumarRSC Adv., 2016,6, 94731-94738 10.1039/C6RA18729C
- [5] Dissociative dynamics of O2 on Ag(110)? Ivor Lon?ari?Phys. Chem. Chem. Phys., 2015,17, 9436-9445 10.1039/C4CP05900J
- [6] Fast synthesis of copper nanoclusters through the use of hydrogen peroxide additive and their application for the fluorescence detection of Hg2+ in water samples? Liao Xiaoqing,Li Ruiyi,Li Zaijun,Sun Xiulan,Wang Zhouping,Liu JunkangNew J. Chem., 2015,39, 5240-5248 10.1039/C5NJ00831J
- [7] Empowering microfluidics by micro-3D printing and solution-based mineral coating? Hongxia Li,Aikifa Raza,Qiaoyu Ge,Jin-You Lu,TieJun ZhangSoft Matter, 2020,16, 6841-6849 10.1039/D0SM00958J
- [8] Fe(ii)-Assisted one-pot synthesis of ultra-small core–shell Au–Pt nanoparticles as superior catalysts towards the HER and ORR? Yi Cao,Yujiao Xiahou,Lixiang Xing,Xiang Zhang,Hong Li,ChenShou Wu,Haibing XiaNanoscale, 2020,12, 20456-20466 10.1039/D0NR04995F
- [9] Emergence of cationic polyamine dendrimersomes: design, stimuli sensitivity and potential biomedical applications Partha Laskar,Christine DufèsNanoscale Adv., 2021,3, 6007-6026 10.1039/D1NA00536G
- [10] Fate of nitrogen-15 in the subsequent growing season of greenhouse tomato plants (Lycopersicon esculentum Mill) as influenced by alternate partial root-zone irrigation Maomao Hou,Fenglin Zhong,Qiu Jin,Enjiang Liu,Jie Feng,Tengyun Wang,Yue GaoRSC Adv., 2017,7, 34392-34400 10.1039/C7RA05271E
Journal Name：MedChemComm
research_products
-
CAS no.: 89640-58-4
![N-(3-cyanothiolan-3-yl)-2-[(2,2,2-trifluoroethyl)sulfanyl]pyridine-4-carboxamide](https://ossimg.kuujia.com/scimg/1444500/1444113-98-7x500.png)
![1,2,3,4,5,6-Hexahydro-[2,3]bipyridinyl-6-ol](https://ossimg.kuujia.com/scimg/1271000/1270529-38-8x500.png)
![2,2-Difluoro-3-[methyl(2-methylbutyl)amino]propanoic acid](https://ossimg.kuujia.com/scimg/2138500/2138166-62-6x500.png)
![2-(1H-indol-3-yl)-N-{[6-(thiophen-2-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}acetamide](https://ossimg.kuujia.com/scimg/2034500/2034271-14-0x500.png)