دانلود رایگان مقاله لاتین تیوزمیکاربازون مس پیچیده از سایت الزویر
عنوان فارسی مقاله:
توپوایزومراز انسانی IB هدف تیوزمیکاربازون مس پیچیده
عنوان انگلیسی مقاله:
Human topoisomerase IB is a target of a thiosemicarbazone copper(II) complex
سال انتشار : 2016
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مقدمه انگلیسی مقاله:
1. Introduction
Human topoisomerase IB (topo IB) is an essential enzyme, which controls the topological state of DNA during replication and transcription processes [1e3]. It has a considerable medical interest because it is the sole cellular target of camptothecins (CPT), a family of compounds used in cancer therapy [4,5], with topotecan and irinotecan approved for clinical use by the FDA [6]. CPT stabilizes the covalent intermediate enzyme-DNA, transforming topo IB in a poison for the cell [7,8]. Other bioactive compounds are able to inhibit topo IB, affecting binding to DNA and/or the chemistry of cleavage reaction [9e11]. Thiosemicarbazones and their metal complexes are a class of compounds exhibiting a wide pharmacological profile. a(N)-heterocyclic thiosemicarbazones have been shown to present anticancer activity [12]. 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (“Triapine”) was found to be effective against leukemia [13] and it has been evaluated in several clinical phase I and II trials [14]. The proposed mode of action of these compounds involves inhibition of ribonucleotide reductase, an enzyme that catalyzes the reduction of ribonucleotides to the corresponding 20 - deoxyribonucleotides during DNA synthesis. Thiosemicarbazones have been suggested to form an iron(III) complex within the cell, which is reduced to the corresponding iron(II) complex. The iron(II) complex may react with oxygen leading to the production of reactive oxygen species (ROS) able to inactivate the tyrosyl free radical that is present in the enzyme structure [15]. Direct reduction of the radical by the iron(II) complex has also been proposed [16]. Another established target for some a(N)-heterocyclic thiosemicarbazones is topoisomerase IIa (Topo IIa), an enzyme regulating DNA topology during cell division [17]. A series of a-(N)- heterocyclic carboxaldehyde thiosemicarbazones proved to have strong affinity for the enzyme, and their anti-proliferative activity was found to correlate with Topo IIa inhibition [18]. In addition, a family of 2-formylpyridine- and 2-acetylpyridine-derived thiosemicarbazones showed Topo IIa inhibition activity, which increased upon complexation with copper(II) with formation of square-planar complexes [19]. As far as topoisomerase I is concerned, enzyme inhibition was reported for zinc(II) complexes with polyhydroxobenzaldehyde derivatives [20]. Chalcones (1,3-diaryl-2-propen-1-ones) are a class of flavonoid natural products consisting of two aryl rings linked by an a,b-unsaturated ketone moiety, with widespread distribution in plants. These compounds possess a variety of biological activities as antioxidant, cytotoxic, anticancer, antimicrobial, antiprotozoal and anti-inflammatory agents [21]. Thiosemicarbazones with a great diversity of structural scaffolds have been investigated but there are not many reports in the literature on chalcone-derived thiosemicarbazones. In previous works a family of chalcone-based thiosemicarbazones and their zinc(II), gallium(III) [22] and copper(II) complexes were prepared [23] and it was shown that coordination to copper(II) significantly increased the cytotoxicity against Jurkat leukemia, against MDA-MB 231 (human breast carcinoma) and HCT-116 (human colorectal carcinoma) cancer cells [23].
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کلمات کلیدی:
Catalytic Mechanism of DNA Topoisomerase IB - ScienceDirect www.sciencedirect.com/science/article/pii/S1097276500802683 by BO Krogh - 2000 - Cited by 158 - Related articles The available crystal structures of vaccinia and human type IB topoisomerases provide no clues to the identity of potential general acid and general base ... Human DNA topoisomerase IB: Structure and functions (PDF ... https://www.researchgate.net/.../6116997_Human_DNA_topoisomerase_IB_Structure_a... Human DNA Topoisomerase I is a 765aa monomeric enzyme composed of four domains: the N-terminal domain, highly charged and responsible for several ... DNA topoisomerase I, domain 1 (IPR013034) < InterPro < EMBL-EBI https://www.ebi.ac.uk/interpro/entry/IPR013034 DNA topoisomerases are divided into two classes: type I enzymes (EC:5.99.1.2; ... The N-terminal domain of human topoisomerase I is thought to coordinate the ... DNA topoisomerase I, eukaryotic-type (IPR013499) < InterPro < EMBL ... www.ebi.ac.uk/interpro/entry/IPR013499 DNA topoisomerases are divided into two classes: type I enzymes ... Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant ... Human Topoisomerase I Inhibitors - Encyclopedia of Life Sciences www.els.net/WileyCDA/ElsArticle/refId-a0026795.html Human topoisomerase IB (Topo IB) is the selective target of camptothecin, a natural compound from which two powerful anticancer drugs, topotecan and ... RCSB PDB - 1A35: HUMAN TOPOISOMERASE I/DNA COMPLEX ... www.rcsb.org/pdb/explore.do?structureId=1a35 1A35: Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. Searches related to Human topoisomerase IB top1 gene top1 protein human topoisomerase ii dna topoisomerase 2 topo1 top1 cancer topoisomerase i inhibitors top 1 indonesia
