New anticancer zinc(II) complexes comprising thiosemicarbazones of saturated ring: structure, DNA/protein binding, DNA cleavage, topoisomerase-1 inhibition and anti-proliferation studies

2016 ◽  
Vol 30 (6) ◽  
pp. 481-487 ◽  
Author(s):  
Vikneswaran Rajamuthy ◽  
Naser Eltaher Eltayeb ◽  
Ramesh Subramaniam ◽  
Yahya Rosiyah
Keyword(s):  
Protein Binding ◽  
Dna Cleavage ◽  
Ring Structure ◽  
Topoisomerase 1 ◽  
Saturated Ring

An investigation on the DNA/protein binding, DNA cleavage and in vitro anticancer properties of SNO pincer type palladium(II) complexes with N-substituted isatin thiosemicarbazone ligands

2017 ◽  
Vol 466 ◽  
pp. 61-70 ◽  
Author(s):  
Mathiyan Muralisankar ◽  
Sabeel M. Basheer ◽  
Jebiti Haribabu ◽  
Nattamai S.P. Bhuvanesh ◽  
Ramasamy Karvembu ◽  
...  
Keyword(s):  
Protein Binding ◽  
Dna Cleavage ◽  
Anticancer Properties

New binuclear Ni(ii) metallates containing ONS chelators: synthesis, characterisation, DNA binding, DNA cleavage, protein binding, antioxidant activity, antimicrobial and in vitro cytotoxicity

2017 ◽  
Vol 41 (7) ◽  
pp. 2543-2560 ◽  
Author(s):  
G. Kalaiarasi ◽  
Ruchi Jain ◽  
H. Puschman ◽  
S. Poorna Chandrika ◽  
K. Preethi ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Dna Binding ◽  
Protein Binding ◽  
Hela Cell ◽  
Antiproliferative Activity ◽  
Dna Cleavage ◽  
In Vitro Cytotoxicity ◽  
Hela Cell Lines ◽  
Mcf 7

Four new binuclear nickel(ii) metallates showed promising antiproliferative activity against MCF-7 and HeLa cell lines and were much less toxic against HaCaT.

A first-in-human, phase I safety and pharmacokinetic study of genz-644282, a non-camptothecin topoisomerase I inhibitor, in patients with advanced solid tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2534-2534
Author(s):  
Hyo S. Han ◽  
Antoinette R. Tan ◽  
Glen J. Weiss ◽  
Daniel Sullivan ◽  
Jonathan R. Strosberg ◽  
...  
Keyword(s):  
Phase I ◽  
Dna Cleavage ◽  
Topoisomerase I ◽  
Safety Data ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Ring Structure ◽  
Small Cell ◽  
Small Cell Lung ◽  
Minor Response

2534 Background: The approved topoisomerase I (TopI) inhibitors (irinotecan and topotecan) are camptothecin derivatives. The lactone ring structure of camptothecins negatively impacts their clinical potential.Genz-644282 is a novel non-camptothecin that induces TopI-DNA cleavage complexes at similar as well as unique genomic positions; that are more persistent. This study was designed using a pharmacokinetic-pharmacodynamic (PK-PD) model to predict the maximum tolerated dose (MTD). Methods: A PK-PD relationship of Genz-644282 to inhibit tumor growth was derived (Simeoni, Can Res 2004). Using an accelerated titration design, cohorts of 1, 3 or 6 patients received 3 weekly doses of Genz-644282 on a 28 day schedule starting with 0.5 mg/m2. After MTD on the 28 day schedule was exceeded, 21 day schedule was initiated. Results: 49 patients (N=44 data available: 26M :18F) were dosed. Tumor types were colorectal (15), breast (5), small cell lung (SCLC 3), non-small cell lung (4), others (17). As predicted from the PK-PD model 8 cohorts were evaluated on the 28 day schedule before defining the MTD. The MTD was 8 mg/m2 and 9 mg/m2 for the 28 day and 21 day schedules, respectively. Dose limiting toxicities that determined the MTD were: gr 4 thrombocytopenia (n=2); gr 2 thrombocytopenia (n=1) and gr 4 neutropenia (n=1) both of which resulted in ≥72h delays in initiating cycle 2. Treatment emergent adverse events (>10%) were nausea (45%), fatigue (39%), anorexia (32%), anemia (27%), vomiting (23%), thrombocytopenia (18%), diarrhea (16%), dehydration (16%), hyperglycemia (16%), cough (16%), dyspnea (14%), depression (11%) and hyponatremia (11%). Efficacy data suggest 2 responders with SCLC (1 minor response;1 complete response), and 2 patients (breast, gastric) with stable disease (≥ 6 months). PK data show a Genz-644282 half-life of approximately 50 h, a linear dose-exposure relationship, and no accumulation in between doses. Conclusions: Genz-644282 is a non-camptothecin TopI inhibitor in phase I development with ongoing expansion phase. The emerging pk, efficacy and safety data are suggestive of a distinct clinical profile of Genz-644282 from the camptothecins.

Synthesis, DNA/protein binding, molecular docking, DNA cleavage and in vitro anticancer activity of nickel(ii) bis(thiosemicarbazone) complexes

RSC Advances ◽  
2015 ◽  
Vol 5 (57) ◽  
pp. 46031-46049 ◽  
Author(s):  
Jebiti Haribabu ◽  
Kumaramangalam Jeyalakshmi ◽  
Yuvaraj Arun ◽  
Nattamai S. P. Bhuvanesh ◽  
Paramasivan Thirumalai Perumal ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Protein Binding ◽  
Anticancer Activity ◽  
Dna Cleavage ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Thiosemicarbazone Complexes ◽  
Ct Dna

Cytotoxic nickel(ii) complexes with an N-substituted isatin thiosemicarbazone were synthesized and their interaction with CT DNA and BSA protein was investigated, which was supported by molecular docking studies.

DNA/protein binding, DNA cleavage, cytotoxicity, superoxide radical scavenging and molecular docking studies of copper(ii) complexes containing N-benzyl-N′-aryl-N′′-benzoylguanidine ligands

2015 ◽  
Vol 2 (8) ◽  
pp. 780-798 ◽  
Author(s):  
Kumaramangalam Jeyalakshmi ◽  
Yuvaraj Arun ◽  
Nattamai S. P. Bhuvanesh ◽  
Paramasivan Thirumalai Perumal ◽  
Anandaram Sreekanth ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Protein Binding ◽  
Dna Cleavage ◽  
Superoxide Radical ◽  
Radical Scavenging ◽  
Docking Studies ◽  
Biological Applications ◽  
Molecular Docking Studies

Copper(ii) complexes containing trisubstituted guanidine ligands were prepared, characterized and evaluated for their biological applications.

Mixed-ligand copper(ii) Schiff base complexes: the role of the co-ligand in DNA binding, DNA cleavage, protein binding and cytotoxicity

2016 ◽  
Vol 45 (22) ◽  
pp. 9073-9087 ◽  
Author(s):  
Wen-Jing Lian ◽  
Xin-Tian Wang ◽  
Cheng-Zhi Xie ◽  
He Tian ◽  
Xue-Qing Song ◽  
...  
Keyword(s):  
Schiff Base ◽  
Dna Binding ◽  
Protein Binding ◽  
Dna Cleavage ◽  
Mixed Ligand ◽  
Schiff Base Complexes ◽  
Biological Features

Four novel mixed-ligand copper(ii) Schiff base complexes were synthesized and characterized. The biological features of the complexes and how acetic auxiliary ligands manipulate these features were investigated.

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