69408-83-9Relevant academic research and scientific papers
Design, synthesis, and evaluation of novel 3-carboranyl-1,8-naphthalimide derivatives as potential anticancer agents
Rykowski, Sebastian,Gurda-Wo?na, Dorota,Orlicka-P?ocka, Marta,Fedoruk-Wyszomirska, Agnieszka,Giel-Pietraszuk, Ma?gorzata,Wyszko, Eliza,Kowalczyk, Aleksandra,St?czek, Pawe?,Bak, Andrzej,Kiliszek, Agnieszka,Rypniewski, Wojciech,Olejniczak, Agnieszka B.
, p. 1 - 43 (2021/03/15)
We synthesized a series of novel 3-carboranyl-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, using click chemistry, reductive amination and amidation reactions and investigated their in vitro effects on cytotoxicity, cell death, cell cycle, and the production of reactive oxygen species in a HepG2 cancer cell line. The analyses showed that modified naphthalic anhydrides and naphthalimides bearing ortho-or meta-carboranes exhibited diversified activity. Naphthalimides were more cytotoxic than naphthalic anhydrides, with the highest IC50 value determined for compound 9 (3.10 μM). These compounds were capable of inducing cell cycle arrest at G0/G1 or G2M phase and promoting apoptosis, autophagy or ferroptosis. The most promising conjugate 35 caused strong apoptosis and induced ROS production, which was proven by the increased level of 2′-deoxy-8-oxoguanosine in DNA. The tested conjugates were found to be weak topoisomerase II inhibitors and classical DNA intercalators. Compounds 33, 34, and 36 fluorescently stained lysosomes in HepG2 cells. Additionally, we performed a similarity-based assessment of the property profile of the conjugates using the principal component analysis. The creation of an inhibitory profile and descriptor-based plane allowed forming a structure–activity landscape. Finally, a ligand-based comparative molecular field analysis was carried out to specify the (un)favorable structural modifications (pharmacophoric pattern) that are potentially important for the quantitative structure– activity relationship modeling of the carborane–naphthalimide conjugates.
Design, antiviral and cytostatic properties of isoxazolidine-containing amonafide analogues
Kokosza, Kamil,Andrei, Graciela,Schols, Dominique,Snoeck, Robert,Piotrowska, Dorota G.
, p. 3135 - 3146 (2015/08/03)
Abstract A novel series of 5-arylcarbamoyl- and 5-arylmethyl-2-methylisoxazolidin-3-yl-3-phosphonates have been synthesized via cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N-substituted naphthalimide acrylamides and N-allylnaphthalimides. All cis- and trans-isoxazolidine phosphonates obtained herein were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-9d and trans-9f exhibited the highest activity (EC50 = 8.9 μM) toward cytomegalovirus. Compounds cis- and trans-9d as well as cis- and trans-9f were found potent against HSV and Vaccinia viruses (EC50 in the 45-58 μM range), whereas isoxazolidines 10a and 10d suppressed replication of Coxsackie B4 and Punta Toro viruses (EC50 in the 45-73 μM range). Antiproliferative evaluation of all obtained isoxazolidines revealed the promising activity of cis-9b, cis-9d, trans-9d, cis-9e, trans-9e, cis-9f and trans-9f toward tested cancer cell lines with IC50 in the 1.1-19 μM range.
Synthesis, photophysical and cytotoxicity evaluations of DNA targeting agents based on 3-amino-1,8-naphthalimide derived Troeger's bases
Murphy, Samantha,Bright, Sandra A.,Poynton, Fergus E.,McCabe, Thomas,Kitchen, Jonathan A.,Veale, Emma B.,Williams, D. Clive,Gunnlaugsson, Thorfinnur
, p. 6610 - 6623 (2014/08/18)
The synthesis and characterisation of five bis-1,8-naphthalimide containing Troeger's bases 1-5 formed from their corresponding 3-amino-1,8- naphthalimide precursors 6-10 is described. The photophysical investigations of 1-5 and 6-10 were carried out in several organic solvents as well as in water and as a function of pH using UV-Vis absorption and fluorescence spectroscopies. The DNA binding affinities of 1-5 in aqueous solution at pH 7.4 were also investigated using several UV-Vis absorption and fluorescence experiments by using calf thymus DNA (ct-DNA). These molecules exhibited significant DNA binding affinities; where large binding values (Kb) in the range of 106 M-1 were determined, even in competitive media (50 mM and 160 mM NaCl at pH 7.4). Thermal denaturation measurements also showed that 1-5 significantly stabilised the DNA helix. Using linear and circular dichroism we further demonstrated that the DNA binding interaction occurs both by intercalation and by groove binding. The Troeger's bases were further shown to be rapidly taken up into cells using confocal fluorescence spectroscopy; and cytotoxic studies in HeLa and MCF-7 cells showed that most of the Troeger's bases were effective cytotoxic agents with EC50 values of between 1.1-12 μM and that all the active compounds induced programmed cell death by apoptosis, where up to 70% cellular death was observed after 24 h of incubation for 4. This journal is the Partner Organisations 2014.
