1207-69-8Relevant academic research and scientific papers
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
, (2019)
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.
Synthesis and Antibacterial Activity of New N9-Substituted Acridine-9-amines
Kudryavtseva,Bogatyrev,Sysoev,Klimova
, p. 157 - 159 (2019)
A method for the synthesis of N9-substituted acridine-9-amines by reacting 9-chloroacridines with 2-(2-methyl-5- nitro-1H-imidazol-1-yl)ethanamine was developed. The synthesized compounds showed high antibacterial ability against B. subtilis bacteria compared with rivanol and metronidazole.
DNA Adduct Detection after Post-Labeling Technique with PCR Amplification (DNA-ADAPT–qPCR) Identifies the Pre-ribosomal RNA Gene as a Direct Target of Platinum–Acridine Anticancer Agents
Yao, Xiyuan,Bierbach, Ulrich
, p. 14681 - 14689 (2021)
To study the DNA damage caused by a potent platinum–acridine anticancer agent (PA) in cancer cells, an assay based on biorthogonal post-labeling using a click chemistry-enabled, azide-modified derivative (APA) was developed. The method involves biotinylation, affinity capture, and bead-based enrichment of APA-modified genomic DNA. The key steps of the assay were validated and optimized in model duplexes, including full-length plasmids, restriction fragments, and a DNA ladder. Native DNA treated with APA and subsequently subjected to post-labeling with a biotin affinity tag was enzymatically digested and fragments were analyzed by in-line LC–MS and MS/MS. The monofunctional–intercalative adducts formed by APA in 5′-pyrimidine/guanine sequences in double-stranded DNA were quantitatively biotinylated by strain-promoted 1,3-dipolar cycloaddition chemistry. When applied to DNA extracted from A549 lung cancer cells, the assay in combination with qPCR amplification demonstrates that platinum–acridines form adducts in the gene sequences encoding pre-ribosomal RNA, a potential pharmacological target of these agents.
Synthesis and biological study of acridine-based imidazolium salts
Sharhan, Olla,Heidelberg, Thorsten,Hashim, Najiahah Mohd,Salman, Abbas Abdulameer,Ali, Hapipah Mohd,Jayash, Soher Nagi
, p. 38995 - 39004 (2018)
A new series of acridine based imidazolium salts was synthesized and evaluated for in vitro cytotoxicity against human cancer cell lines by an MTT assay. The synthesis applied a coupling of imidazoles with 9-chloroacridines, which originated from an Ullmann condensation of a 2-chloro-benzoic acid with an aniline. The target compounds were obtained in high yields. The DPPH assay indicated considerable antioxidant activity for target compounds with simple and short alkyl chains on the imidazole, while increasing chain length and the introduction of an additional π-electron system in most cases reduced the activity. All compounds exhibited low biotoxicity against non-cancerous cell lines, whereas a few compounds showed promising anticancer activity. Unlike for the reference drugs Tamoxifen and Paclitaxel, the anticancer activity of acridine imidazolium ions is specific for only selected cancer types. Reasonable fluorescent behaviour of the products provide potential for visualization of the distribution of active drugs in tissue.
Interaction of acridine-calix[4]arene with DNA at the electrified liquid|liquid interface
Kivlehan, Francine,Lefoix, Myriam,Moynihan, Humphrey A.,Thompson, Damien,Ogurtsov, Vladimir I.,Herzog, Grégoire,Arrigan, Damien W.M.
, p. 3348 - 3354 (2010)
The behaviour of an acridine-functionalised calix[4]arene at the interface between two immiscible electrolyte solutions (ITIES) is reported. Molecular modelling showed that the acridine-calix[4]arene has regions of significant net positive charge spread throughout the protonated acridine moieties, consistent with it being able to function as an anion ionophore. The presence of this compound in the organic phase facilitated the transfer of aqueous phase electrolyte ions. Upon addition of double stranded DNA to the aqueous phase, the transfer of electrolyte anions was diminished, due to DNA binding to the acridine moiety at the ITIES. The behaviour provides a basis for DNA hybridization detection using electrochemistry at the ITIES.
Potential DNA bis-intercalating agents. Synthesis and antitumor activity of N,N-Methylenedi-4,1-cyclohexanediyl- bis(9-acridinamine) isomers
Gribble, Gordon W.,Mosher, Michael D.,Jaycox, Gary D.,Cory, Michael,Fairley, Terri A.
, p. 535 - 546 (2014)
We describe the synthesis and antitumor activity of three novel isomeric bis-acridines 14-16 possessing a non-aromatic, semi-rigid dicyclohexylmethylene tether.
Effects of the Distance between Radical Sites on the Reactivities of Aromatic Biradicals
Ding, Duanchen,Jiang, Hanning,Ma, Xin,Nash, John J.,Kentt?maa, Hilkka I.
, p. 8415 - 8428 (2020)
Coupling of the radical sites in isomeric benzynes is known to hinder their radical reactivity. In order to determine how far apart the radical sites must be for them not to interact, the gas-phase reactivity of several isomeric protonated (iso)quinoline-and acridine-based biradicals was examined. All the (iso)quinolinium-based biradicals were found to react slower than the related monoradicals with similar vertical electron affinities (i.e., similar polar effects). In sharp contrast, the acridinium-based biradicals, most with the radical sites farther apart than in the (iso)quinolinium-based systems, showed greater reactivities than the relevant monoradicals with similar vertical electron affinities. The greater distances between the two radical sites in these biradicals lead to very little or no spin-spin coupling, and no suppression of radical reactivity was observed. Therefore, the radical sites can still interact if they are located on adjacent benzene rings and only after being separated further than that does no coupling occur. The most reactive radical site of each biradical was experimentally determined to be the one predicted to be more reactive based on the monoradical reactivity data. Therefore, the calculated vertical electron affinities of relevant monoradicals can be used to predict which radical site is most reactive in the biradicals.
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 (2020)
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.
Novel 9-(2-(1-arylethylidene)hydrazinyl)acridine derivatives: Target Topoisomerase 1 and growth inhibition of HeLa cancer cells
Haider, Md Rafi,Ahmad, Kamal,Siddiqui, Nadeem,Ali, Zulphikar,Akhtar, Md Jawaid,Fuloria, Neeraj,Fuloria, Shivkanya,Ravichandran, Manickam,Yar, M. Shahar
, (2019)
A series of 9-(2-(1-arylethylidene)hydrazinyl)acridine and its analogs were designed, synthesized and evaluated for biological activities. Various biochemical assays were performed to determine the free radical scavenging capacity of synthesized compounds (4a–4j). Anticancer activity of these compounds was assessed against two different human cancer cell lines viz cervical cancer cells (HeLa)and liver cancer cells (HepG2)as well as normal human embryonic kidney cell line (HEK 293). Compounds 4b, 4d and 4e showed potential anti-proliferative effects on HeLa cells. Based on results obtained from antioxidant and cytotoxicity studies, 4b, 4d and 4e were further studied in detail for different biological activities. 4b, 4d and 4e reduced the cell growth, inhibited metastatic activity and declined the potential of cell migration in HeLa cell lines. Topoisomerase1 (Top1)treated with compounds 4b, 4d and 4e exhibited inhibition of Top1 and prevented DNA replication. Molecular docking results validate that interaction of compounds 4b, 4d and 4e with Top1-DNA complex, which might be accountable for their inhibitory effects. Further it was concluded that compounds 4b, 4d and 4e arrests the cells at S phase and consequently induces cell death through DNA damage in HeLa cells.
Novel synthetic acridine-based derivatives as topoisomerase i inhibitors
Li, Bin,Gao, Chun-Mei,Sun, Qin-Sheng,Li, Lu-Lu,Tan, Chun-Yan,Liu, Hong-Xia,Jiang, Yu-Yang
, p. 1021 - 1024 (2014)
Novel DNA binding agents against topoisomerases are needed for effective treatment of cancers. A series of new acridine-based derivatives 7a-7d were synthesized and their antiproliferative activity against K562 and HepG-2 cell lines were evaluated. Compound 7c with pyridin-2-yl-methanamino group substituted at the C9 position of acridine showed good antitumor activity against both cell lines. The DNA-binding affinity of compound 7c was evaluated by UV-vis absorption spectra and fluorescence emission spectra. DNA topoisomerase I mediated relaxation of plasmid pBR322 DNA was also tested. Our results suggested that compound 7c with good antitumor activity and topoisomerase I inhibition activity can be developed as a prime candidate for further chemical optimization.
