17981-81-6Relevant articles and documents
Semi-automatic synthesis, antiproliferative activity and DNA-binding properties of new netropsin and bis-netropsin analogues
Szerszenowicz, Jakub,Drozdowska, Danuta
, p. 11300 - 11315 (2014)
A general route for the semi-automatic synthesis of some new potential minor groove binders was established. Six four-numbered sub-libraries of new netropsin and bis-netropsin analogues have been synthesized using a Syncore Reactor. The structures of the
A spiropyran-coumarin platform: An environment sensitive photoresponsive drug delivery system for efficient cancer therapy
Barman, Shrabani,Das, Joyjyoti,Biswas, Sandipan,Maiti,Pradeep Singh
, p. 3940 - 3944 (2017)
In spite of inventing several anticancer agents the clinical payoff still remains unsatisfactory because of their severe host toxicity due to their nonspecific biodistribution in the body. To achieve high efficiency in anti-cancer drug delivery, thus, we designed and developed a single component photoresponsive drug delivery system, a fusion of two platforms spiropyran and coumarin, which synchronizes two controlling factors: first, the lower pH of cancer tissue, which acts as an internal control and leads to the ring opening of spiropyran resulting in a distinct colour change and fluorescence activation of coumarin; and second, the release of the anti-tumor drug by the externally controlled light. Highly fluorescent nature and promising biocompatibility make the SP-Cou-Cbl system suitable for cell imaging and in vitro studies.
Synthesis and preliminary biological evaluation of a 99mTc-chlorambucil derivative as a potential tumor imaging agent
Lin, Jianguo,Qiu, Ling,Lv, Gaochao,Li, Ke,Wang, Wei,Liu, Guiqing,Zhao, Xueyu,Wang, Shanshan
, p. 116 - 123 (2017)
Technetium-99m-based radiopharmaceuticals have been used widely as diagnostic agents in the nuclear medicine. Chlorambucil (CLB) as one typical alkylating drug exhibits excellent inhibition effects against many human malignancies. To develop and explore a
Peptide-Driven Targeted Drug-Delivery System Comprising Turn-On Near-Infrared Fluorescent Xanthene–Cyanine Reporter for Real-Time Monitoring of Drug Release
Ebaston,Rozovsky, Alex,Zaporozhets, Alisa,Bazylevich, Andrii,Tuchinsky, Helena,Marks, Vered,Gellerman, Gary,Patsenker, Leonid D.
, p. 1727 - 1734 (2019)
Targeted drug delivery (TDD) is an efficient strategy for cancer treatment. However, the real-time monitoring of drug delivery is still challenging because of a pronounced lack of TDD systems capable of providing a near-infrared (NIR) fluorescence signal for the detection of drug-release events. Herein, a new TDD system, comprising a turn-on NIR fluorescent reporter attached to an anticancer drug and targeting peptide, is reported. This system provides both TDD and NIR fluorescence monitoring of drug-release events in target tissue. In this TDD system, a new carboxy-derivatized xanthene–cyanine (XCy) dye is attached to an anticancer drug, chlorambucil (CLB), through a hydrolytically cleavable ester linker and coupled to a targeting peptide, octreotide amide (OCTA), which is specific to somatostatin receptors SSTR-2 and STTR-5 overexpressed on many tumor cells. This OCTA-G-XCy-CLB (G: γ-aminobutyric acid) conjugate exhibits no detectable fluorescence, whereas, upon the hydrolytic cleavage of the ester linker, a bright NIR fluorescence appears at λ≈710 nm; this signals release of the drug. Real-time TDD monitoring is demonstrated for the example of the human pancreatic cancer cell line overexpressing SSTR-2 and STTR-5, in comparison with the noncancerous Chinese hamster ovary cell line, which contains a reduced number of these receptors.
Synthesis, molecular modelling, and antiproliferative and cytotoxic effects of carbocyclic derivatives of distamycin with chlorambucil moiety
Bartulewicz, Danuta,Bielawski, Krzysztof,Bielawska, Anna,Rozanski, Andrzej
, p. 461 - 467 (2001)
New carbocylic analogues of distamycin and netropsin with chlorambucil moieties 5-8 have been synthesised. Data from the ethidium displacement assay showed that these compounds bind in the minor groove of DNA. The observed reduced affinity to AT pairs and increased affinity towards GC sequences of the carbocyclic lexitropsins with chlorambucil moiety 5-8 in comparison with netropsin and distamycin was observed and rationalised by means of molecular modelling techniques. All of the compounds 5-8 showed antiproliferative and cytotoxic effects in the standard cell line of the mammalian tumour MCF-7.
1,3-Dipalmitoylglycerol ester of chlorambucil as a lymphotropic, orally administrable antineoplastic agent
Garzon-Aburbeh,Poupaert,Claesen,Dumont,Atassi
, p. 1200 - 1203 (1983)
A glyceridere derivative of chlorambucil (2), 1,3-dipalmitoyl-2-[4-[bis(2-chloroethyl)amino]benzenebutanoyl]glycerol (1), was synthesized and tested as an orally administrable antineoplastic drug endowed with lymphotropic properties. A significantly highe
1 - {3 - [To - double - (2 - chloroethyl) amino] amphetamine yl} carbamoyl -5 - eadm and its preparation and use
-
Paragraph 0126-0130, (2019/03/15)
The invention discloses a structure of the formula I of the antineoplastic compound: 1 - {3 - [to - double - (2 - chloroethyl) amino] amphetamine yl} carboxamido - 5 - Fluorouracil and its preparation method. The present invention of said pharmaceutical c
Rational design and characterization of a DNA/HDAC dual-targeting inhibitor containing nitrogen mustard and 2-aminobenzamide moieties
Xie, Rui,Tang, Pingwah,Yuan, Qipeng
, p. 344 - 352 (2018/03/08)
Histone deacetylases (HDACs) play a key role not only in gene expression but also in DNA repair. Herein, we report the rational design and characterization of a compound named chlordinaline containing nitrogen mustard and 2-aminobenzamide moieties as a DNA/HDAC dual-targeting inhibitor. Chlordinaline exhibited moderate total HDAC inhibitory activity. The HDAC isoform selectivity assay indicated that chlordinaline mostly inhibits HDAC3. Chlordinaline exhibited both DNA and HDAC inhibitory activities and showed potent antiproliferative activity against all the six test cancer cell lines with IC50 values of as low as 3.1-14.2 μM, which is significantly more potent than reference drugs chlorambucil and tacedinaline. Chlordinaline could induce the apoptosis and G2/M phase cell cycle arrest of A375 cancer cells. This study demonstrates that combining nitrogen mustard and 2-aminobenzamide moieties into one molecule is an effective method to obtain DNA/HDAC dual-targeting inhibitors as potent antitumor agents. Chlordinaline as the first example of such DNA/HDAC dual-targeting inhibitors could be a promising candidate for cancer therapy and could also be a lead compound for further optimization.
5' - Deoxy - 5 - fluoro - N - {4 - [double (2 - chloroethyl) amino] benzene ding acyl} cytidine and its preparation method and application
-
Paragraph 0113; 0115, (2018/04/20)
The invention discloses a medicine molecule with a structure as shown in a formula I which is described in the specificatioin, i.e., 5'-deoxy-5-fluoro-N-{4-[bis(2-chloroethyl)amino]benzobutyryl}cytidine, and a preparation method thereof. The medicine mole
New approach of delivering cytotoxic drugs towards CAIX expressing cells: A concept of dual-target drugs
van Kuijk, Simon J.A.,Parvathaneni, Nanda Kumar,Niemans, Raymon,van Gisbergen, Marike W.,Carta, Fabrizio,Vullo, Daniela,Pastorekova, Silvia,Yaromina, Ala,Supuran, Claudiu T.,Dubois, Ludwig J.,Winum, Jean-Yves,Lambin, Philippe
, p. 691 - 702 (2017/02/18)
Carbonic anhydrase IX (CAIX) is a hypoxia-regulated and tumor-specific protein that maintains the pH balance of cells. Targeting CAIX might be a valuable approach for specific delivery of cytotoxic drugs, thereby reducing normal tissue side-effects. A ser
