China
Africa
Explore chapters and articles related to this topic
Tuning of Ruthenium – DMSO Complexes for Search of New Anticancer Agents
Published in Ajay Kumar Mishra, Lallan Mishra, Ruthenium Chemistry, 2018
On the other hand, topoisomerase II enzyme is crucial for the cellular division of rapidly growing proliferating tumor cells. Therefore, the inhibition of topo II has also been primary targeted for numerous antitumor agents (Larsen et al., 2003; Nitiss et al., 2009). The nuclear enzyme topoisomerase II is referred to as a “molecular engineer,” which is essential for DNA replication, repair, transcription, topological changes, and chromosomal segregation at mitosis under physiological condition (Spence, 2005). The topoisomerase catalyzes the transient double strand of DNA, transport it into an intact fragment of DNA and relegate cleaved strands. The enzyme is a combination of three domains: (1) N-terminal ATP-binding domain: various catalytic inhibitors reduce ATPase activity by blocking ATP from its binding site, (2) DNA-binding/cleaving domain: catalytic active site necessary for construction of covalent complex, and (3) C-terminal tail (Bailly, 2012). To understand the mechanism of action, two categories of Topo II inhibitors were studied in detail: (1) those that form DNA−Topo-II cleavable complex by binding with the topo II and stimulate the cleavage of double standard DNA (etoposide) (Zeglis, 2011), (2) other class, which includes catalytic inhibitors which antagonize the activity of enzyme to implement catalysis (merbarone) Larsen (2003). The wide range of topoisomerase inhibitors, including etoposide, mitoxantrone, amsacrine, idarubicin, and doxorubicin mainly destroy all cells in DNA replication and sensing of DNA in protein production or DNA-damage repair (Li, 2001). The topoisomerase inhibition is fundamentally influenced by the nature of complexes, ligands, and available uncoordinated sites in the skeleton of coordinated ligands. In this connection, Jayaraju et al. reported topo II inhibitor salicylaldoxime cobalt complex (CoSAL), which results in cleavable complex formation by interacting oxime moiety of the salicylaldoxime ligand with the topo II (Jayaraju, 1999). Furthermore, (η6-benzene)Ru(DMSO)Cl2 (Fig. 10.3)displayed strong DNA-binding affinity together with cross-linking with topoisomerase II and inhibited the activity of topoisomerase II by cleavage complex formation (Gopal, 2002). Gopal et al. suggested that ruthenium complex interacts with DNA and forms cross-links with topoisomerase II. The complex exhibited antiproliferative activity in two human cancer cell lines Colo-205 (colon adenocarcinoma) and ZR-75-1 (breast carcinoma) in vitro, but it is inconclusive if there is a direct link to its ability to inhibit topoisomerase II activity (Gopal, 2002).
Ultrasound-assisted synthesis of 1, 8-dioxodecahydroacridine derivatives in presence of Ag doped CdS nanocatalyst
Published in Journal of Dispersion Science and Technology, 2020
Divya Verma, Vikash Sharma, Shubha Jain, Gunadhor Singh Okram
Acridine derivatives are among the oldest and most attractive heteroaromatic structures. They constitute a class of bioactive agents that are being intensively studied because of their broad biological activities and hence applications. Acridine analogs exhibit several medicinal applications (Figure 1) including anti-bacterial (S-303),[1] anti-malarial (Quinacrine),[2] anti-HIV, (CGP40336A),[3,4] anti-cancer chemotherapeutics (N-(2-(dimethylamino) ethyl)acridine-4-carboxamide (DACA), nitracrine, amsacrine),[1] anti-fungal,[5] anti-tumors,[6] anti-glaucoma[7] agents and laser dyes due to their high fluorescence efficiency.[6] These examples have their own significance like S-303, binds and inactivates the genomes of bacterial and viral pathogens in plasma and red blood cell preparations destined for clinical testing or transfusion. Quinacrine, an anti-malerial drug, has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. CGP40336A inhibit tat-TAR interaction and represents another significant lead for the development of anti-HIV drugs. DACA inhibit two enzymes: topo I and II. This unusual property of DACA and its derivatives was studied using x-ray evaluation of complexes formed with DNA sequences. Nitracrine was also clinically used for several years and Amsacrine (m-AMSA) was the first synthetic drug of the DNA-intercalating type to show clinical efficiency. The synthetic protocols for acridinone have been therefore intensively pursued during the past decade using mostly acid-catalyzed processes[8–31] focusing on the design of target acridine skeletons. The basic importance of acid catalysts in all the processes is that the amount and acidic strength of the catalyst play a vital role to achieve better yields. However, the preparation process of the reported catalysts is tedious and not so cost-effective. Therefore, development of a novel, efficient and heterogeneous acid catalyst with suitable feedstock for this process is of great interest.