Study of New Ferrocene Incorporated N,N′-Disubstituted Thioureas as Potential Antitumour Agents

In this paper, we report the synthesis, structural characterisation, cytotoxicity against human ovarian tumour models (A2780, A2780cisR, and A2780ZD0473R), nature of interaction with calf-thymus (CT)-DNA and pBR322 plasmid DNA of new ferrocene based N,N′-disubstituted thioureas (3a–d). The compounds, characterized based on elemental analysis, FT-IR and multinuclear (1H and 13C) NMR spectroscopy, and single crystal X-ray diffractometry, were found to have significant antitumour activity although much less than cisplatin. Crystallographic data reveals the existance of secondary interactions for compound 3c in terms of intermolecular hydrogen bonding of type NH⋯O, NH⋯S and secondary non-covalent interactions (π⋯H). When pBR322 plasmid DNA was interacted with increasing concentrations of compounds, 3a and 3b but not 3c were found to partially prevent BamH1 digestion of the DNA. The negative shift in peak potential in voltammetric measurements indicates that all the compounds undergo electrostatic interactions with the negatively charged phosphate DNA backbone. The large negative value of the binding energy indicates the spontaneity of reaction between the compounds and CT-DNA and the conformational stability of adducts formed.

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Studies of the Antiproliferative Activity of Ruthenium (II) Cyclopentadienyl-Derived Complexes with Nitrogen Coordinated Ligands

Bioinorganic Chemistry and Applications ◽

10.1155/2010/936834 ◽

2010 ◽

Vol 2010 ◽

pp. 1-11 ◽

Cited By ~ 28

Author(s):

Virtudes Moreno ◽

Julia Lorenzo ◽

Francesc X. Aviles ◽

M. Helena Garcia ◽

João P. Ribeiro ◽

...

Keyword(s):

Plasmid Dna ◽

Antitumor Agents ◽

Tertiary Structure ◽

Base Pairs ◽

Force Microscopy ◽

Atomic Force ◽

Dna Base ◽

Dna Base Pairs ◽

Pbr322 Plasmid ◽

Ct Dna

Four cationic ruthenium(II) complexes with the formula[Ru(η5-C5H5)(PPh3)2]+, withL=5-phenyl-1H-tetrazole (TzH)1, imidazole (ImH)2, benzo[1,2-b;4,3-b′] dithio-phen-2-carbonitrile (Bzt)3, and [5-(2-thiophen-2-yl)-vinyl]-thiophene-2-carbonitrile] (Tvt)4were prepared and characterized in view to evaluate their potentialities as antitumor agents. Studies by Circular Dichroism indicated changes in the secondary structure of ct-DNA. Changes in the tertiary structure of pBR322 plasmid DNA were also observed in gel electrophoresis experiment and the images obtained by atomic force microscopy (AFM) suggest strong interaction with pBR322 plasmid DNA; the observed decreasing of the viscosity with time indicates that the complexes do not intercalate between DNA base pairs. Compounds1,2, and3showed much higher cytotoxicity than the cisplatin against human leukaemia cancer cells (HL-60 cells).

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The water soluble peripherally tetra-substituted zinc(ii), manganese(iii) and copper(ii) phthalocyanines as new potential anticancer agents

Dalton Transactions ◽

10.1039/c6dt02720b ◽

2016 ◽

Vol 45 (36) ◽

pp. 14301-14310 ◽

Cited By ~ 25

Author(s):

Burak Barut ◽

Ayşenur Sofuoğlu ◽

Zekeriya Biyiklioglu ◽

Arzu Özel

Keyword(s):

Anticancer Agents ◽

Plasmid Dna ◽

Water Soluble ◽

Ethoxy Group ◽

Pbr322 Plasmid ◽

Ct Dna

In this study, [2-(2-morpholin-4-ylethoxy)ethoxy] group substituted zinc(ii), manganese(iii) and copper(ii) phthalocyanines 2–4 and their water soluble derivatives 2a, 3a and 4a were synthesized and the interactions of compounds 2a, 3a and 4a with CT-DNA and supercoiled pBR322 plasmid DNA were investigated.

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Synthesis, DNA-binding and antiproliferative activity of N-(Nitrogen heterocyclic) norcantharidin acylamide acid

Open Chemistry ◽

10.2478/s11532-009-0058-3 ◽

2009 ◽

Vol 7 (3) ◽

pp. 569-575 ◽

Cited By ~ 4

Author(s):

Wen-Zhong Zhu ◽

Rui-Ding Hu ◽

Qiu-Yue Lin ◽

Xiao-Xia Wang ◽

Xiao-Liang Zheng

Keyword(s):

Dna Binding ◽

Cell Line ◽

Elemental Analysis ◽

Antiproliferative Activity ◽

Plasmid Dna ◽

H Nmr ◽

Smmc7721 Cell ◽

Calf Thymus ◽

Binding Experiment ◽

Pbr322 Plasmid

AbstractTwo novel norcantharidin acylamide acids (HL1=N-pyrimidine norcantharidin acylamide acid, C12H13N3O4; HL2=N-pyridine norcantharidin acylamide acid, C13H14N2O4) were synthesized by a reaction of norcantharidin(NCTD) with 2-aminopyrimidine and 2-aminopyridine, respectively. Their structures were characterized by elemental analysis, IR, UV and 1 H NMR. Fluorescence titration and viscosity measurements indicated that HL1, HL2 and HL3 (HL3=N-phenyl norcantharidin acylamide acid, C14H15NO4) can bind calf thymus DNA via partial intercalation. The liner Stern-Volmer quenching constant Ksv values for HL1, HL2 and HL3 were 2.05 × 104 L mol−1, 1.15 × 104 L mol−1 and 8.30×103 L mol−1, respectively. Two compounds containing heterocycle of HL1 and HL2 have been found to cleave pBR322 plasmid DNA at physiological pH and temperature. The test of antiproliferation activity showed that the compounds had moderate to strong antiproliferative ability against the tested cell lines except of HL3 against the SMMC7721 cell line. The results indicated that the heterocycle attached to the norcantharidin was favorable to antiproliferative activity. This result was consistent with the DNA binding experiment.

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ATP and Tri-Polyphosphate (TPP) Suppress Protein Aggregate Growth by a Supercharging Mechanism

Biomedicines ◽

10.3390/biomedicines9111646 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1646

Author(s):

Jordan Bye ◽

Kiah Murray ◽

Robin Curtis

Keyword(s):

Protein Interactions ◽

Electrostatic Interactions ◽

Colloidal Stability ◽

Conformational Stability ◽

Kinetic Studies ◽

Structural Factors ◽

Protein Protein Interactions ◽

Protein Aggregate ◽

Aggregate Growth

A common strategy to increase aggregation resistance is through rational mutagenesis to supercharge proteins, which leads to high colloidal stability, but often has the undesirable effect of lowering conformational stability. We show this trade-off can be overcome by using small multivalent polyphosphate ions, adenosine triphosphate (ATP) and tripolyphosphate (TPP) as excipients. These ions are equally effective at suppressing aggregation of ovalbumin and bovine serum albumin (BSA) upon thermal stress as monitored by dynamic and static light scattering. Monomer loss kinetic studies, combined with measurements of native state protein–protein interactions and ζ-potentials, indicate the ions reduce aggregate growth by increasing the protein colloidal stability through binding and overcharging the protein. Out of three additional proteins studied, ribonuclease A (RNaseA), α-chymotrypsinogen (α-Cgn), and lysozyme, we only observed a reduction in aggregate growth for RNaseA, although overcharging by the poly-phosphate ions still occurs for lysozyme and α-Cgn. Because the salts do not alter protein conformational stability, using them as excipients could be a promising strategy for stabilizing biopharmaceuticals once the protein structural factors that determine whether multivalent ion binding will increase colloidal stability are better elucidated. Our findings also have biological implications. Recently, it has been proposed that ATP also plays an important role in maintaining intracellular biological condensates and preventing protein aggregation in densely packed cellular environments. We expect electrostatic interactions are a significant factor in determining the stabilizing ability of ATP towards maintaining proteins in non-dispersed states in vivo.

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HPMA copolymer platinates as novel antitumour agents: in vitro properties, pharmacokinetics and antitumour activity in vivo

European Journal of Cancer ◽

10.1016/s0959-8049(99)00030-1 ◽

1999 ◽

Vol 35 (6) ◽

pp. 994-1002 ◽

Cited By ~ 139

Author(s):

E Gianasi ◽

M Wasil ◽

E.G Evagorou ◽

A Keddle ◽

G Wilson ◽

...

Keyword(s):

Antitumour Activity ◽

Hpma Copolymer ◽

Antitumour Agents

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Factors affecting the transformation of Escherichia coli strain χ1776 by pBR322 plasmid DNA

Gene ◽

10.1016/0378-1119(78)90038-0 ◽

1978 ◽

Vol 3 (4) ◽

pp. 279-292 ◽

Cited By ~ 109

Author(s):

Michael V. Norgard ◽

Kirsten Keem ◽

John J. Monahan

Keyword(s):

Escherichia Coli ◽

Plasmid Dna ◽

Coli Strain ◽

Factors Affecting ◽

Pbr322 Plasmid

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Amplification of pBR322 plasmid DNA inEscherichia coli relA strains during batch and fed-batch fermentation

Journal of Basic Microbiology ◽

10.1002/jobm.3620300111 ◽

1990 ◽

Vol 30 (1) ◽

pp. 37-41 ◽

Cited By ~ 22

Author(s):

K. H. Hofmann ◽

P. Neubauer ◽

Sabine Riethdorf ◽

M. Hecker

Keyword(s):

Plasmid Dna ◽

Batch Fermentation ◽

Inescherichia Coli ◽

Fed Batch ◽

Fed Batch Fermentation ◽

Pbr322 Plasmid

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Synthesis and Pharmacological Evaluation of Novel Homocamptothecin-Dihydropyridine Derivative Conjugates as Potent Topoisomerase I Inhibitors

Australian Journal of Chemistry ◽

10.1071/ch11091 ◽

2011 ◽

Vol 64 (10) ◽

pp. 1390 ◽

Cited By ~ 5

Author(s):

Ling-Jian Zhu ◽

Chun-Lin Zhuang ◽

Ning Lei ◽

Chun-Quan Sheng ◽

Wei Guo ◽

...

Keyword(s):

Topoisomerase I ◽

Antitumour Activity ◽

Tumour Cell Line ◽

Dna Topoisomerase I ◽

Inhibition Activity ◽

Dna Topoisomerase ◽

Antitumour Agents ◽

Topoisomerase I Inhibitors ◽

Dihydropyridine Derivative ◽

New Generation

Homocamptothecins (hCPT) represent a new generation of antitumour agents targeting DNA topoisomerase I. The expanded seven-membered lactone E-ring that characterizes hCPT enhances the plasma stability of the drug and reinforces the inhibition of topoisomerase I (Topo I) compared with conventional six-membered CPT. In an attempt to improve the antitumour activity of hCP, a series of novel hCPT derivatives conjugating with dihydropyridine derivates were designed and synthesized based on a synthetic route that couples 7-formylhomocamptothecin with different dihydropyridine derivates. Most of the synthesized compounds exhibited good cytotoxic activity on tumour cell line A549, MDA-MB-435, and HCT116. Furthermore, this class of compounds showed superior Topo I inhibition activity comparable to or higher than CPT.

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