86-38-4Relevant articles and documents
Synthesis and antiproliferative activity of 9-benzylamino-6-chloro-2-methoxy-acridine derivatives as potent DNA-binding ligands and topoisomerase II inhibitors
Zhang, Wei,Zhang, Bin,Zhang, Wei,Yang, Ti,Wang, Ning,Gao, Chunmei,Tan, Chunyan,Liu, Hongxia,Jiang, Yuyang
, p. 59 - 70 (2016)
A series of 9-benzylamino acridine derivatives were synthesized as an extension of our discovery of acridine antitumor agents. Most of these acridine compounds displayed good antiproliferative activity with IC50 values in low micromole range and structure-activity relationships were studied. Topo I- and II- mediated relaxation studies suggested that all of our compounds displayed strong Topo II inhibitory activity at 100 μM, while only four exhibited moderate Topo I inhibitory activity. The typical compound 8p could penetrate A549 cancer cells efficiently. Compound 8p could intercalate within the double-stranded DNA structure and induce DNA damage. Moreover, compound 8p could induce A549 cells apoptosis through caspase-dependent intrinsic pathway and arrest A549 cells at the G2/M phase.
Design, synthesis and characterization of novel quinacrine analogs that preferentially kill cancer over non-cancer cells through the down-regulation of Bcl-2 and up-regulation of Bax and Bad
Solomon, V. Raja,Almnayan, Danah,Lee, Hoyun
, p. 156 - 166 (2017)
Both quinacrine, which contains a 9-aminoacridine scaffold, and thiazolidin-4-one are promising anticancer leads. In an attempt to develop effective and potentially safe anticancer agents, we synthesized 23 novel hybrid compounds by linking the main structural unit of the 9-aminoacridine ring with the thiazolidin-4-one ring system, followed by examination of their anticancer effects against three human breast tumor cell lines and matching non-cancer cells. Most of the hybrid compounds showed good activities, and many of them possessed the preferential killing property against cancer over non-cancer cells. In particular, 3-[3-(6-chloro-2-methoxy-acridin-9-ylamino)-propyl]-2-(2,6-difluoro-phenyl)-thiazolidin-4-one (11; VR118) effectively killed/inhibited proliferation of cancer cells at IC50 values in the range of 1.2–2.4 μM. Furthermore, unlike quinacrine or cisplatin, compound 11 showed strong selectivity for cancer cell killing, as it could kill cancer cells 7.6-fold (MDA-MB231 vs MCF10A) to 14.7-fold (MCF7 vs MCF10A) more effectively than matching non-cancer cells. Data from flow cytometry, TUNEL and Western blot assays showed that compound 11 kills cancer cells by apoptosis through the down-regulation of Bcl-2 (but not Bcl-XL) survival protein and up-regulation of Bad and Bax pro-apoptotic proteins. Thus, compound 11 is a highly promising lead for an effective and potentially anticancer therapy.
Design, synthesis and biological evaluation of novel phthalazinone acridine derivatives as dual PARP and Topo inhibitors for potential anticancer agents
Dai, Qiuzi,Chen, Jiwei,Gao, Chunmei,Sun, Qinsheng,Yuan, Zigao,Jiang, Yuyang
, p. 404 - 408 (2019/06/24)
In this study, we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors. MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation. In addition, all the compounds displayed Topo II inhibition activity at 10 mol/L, and also possessed good PARP-1 inhibitory activities. Subsequent mechanistic studies showed that compound 9a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells. Our study suggested that 9a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.
Design, synthesis and biological research of novel N-phenylbenzamide-4-methylamine acridine derivatives as potential topoisomerase I/II and apoptosis-inducing agents
Zhang, Bin,Dou, Zhende,Xiong, Zheng,Wang, Ning,He, Shan,Yan, Xiaojun,Jin, Haixiao
supporting information, (2019/10/28)
A series of novel N-phenylbenzamide-4-methylamine acridine derivatives were designed and synthesized based initially on the structure of amsacrine (m-AMSA). Molecular docking suggested that the representative compound 9a had affinity for binding DNA topoisomerase (Topo) II, which was comparable with that of m-AMSA, and furthermore that 9a could have preferential interactions with Topo I. After synthesis of 9a and analogues 9b-9f, these were all tested in vitro and the synthesized compounds displayed potent antiproliferative activity against three different cancer cell lines (K562, CCRF-CEM and U937). Among them, compounds 9b, 9c and 9d exhibiting the highest activity with IC50 value ranging from 0.82 to 0.91 μM against CCRF-CEM cells. In addition, 9b and 9d also showed high antiproliferative activity against U937 cells, with IC50 values of 0.33 and 0.23 μM, respectively. The pharmacological mechanistic studies of these compounds were evaluated by Topo I/II inhibition, western blot assay and cell apoptosis detection. In summary, 9b effectively inhibited the activity of Topo I/II and induced DNA damage in CCRF-CEM cells and, moreover, significantly induced cell apoptosis in a concentration-dependent manner. These observations provide new information and guidance for the structural optimization of more novel acridine derivatives.
