Molecular drug design, synthesis and crystal structure determination of CuII–SnIV heterobimetallic core: DNA binding and cleavage studies

Autor: Mohd Afzal, Loïc Toupet, Shazia Parveen, Taibi Ben Hadda, Farukh Arjmand
Přispěvatelé: Faculté des sciences [Oujda], Université Mohammed Premier [Oujda], Institut de Physique de Rennes (IPR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Department of Biotechnology, New Delhi (SchemeNo.BT/PR9205/Med/30/13/2007), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2012
Předmět:
Models
Molecular
Intercalation (chemistry)
Crystal structure
MESH: Drug Design
Crystallography
X-Ray
01 natural sciences
chemistry.chemical_compound
Coordination Complexes
MESH: Coordination Complexes
Topo I inhibition activity
Drug Discovery
MESH: Phenanthrolines
MESH: Animals
MESH: DNA Cleavage
MESH: Tin
chemistry.chemical_classification
biology
MESH: DNA
General Medicine
Ligand (biochemistry)
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biomolecules [q-bio.BM]
MESH: Copper
MESH: Cattle
MESH: Topoisomerase I Inhibitors
MESH: Nucleic Acid Conformation
DNA Topoisomerases
Type I
CuII-SnIV phen complex
CT DNA binding
Molecular docking
Pharmacophore
MESH: Models
Molecular
Phenanthrolines
pBR322 DNA cleavage
Stereochemistry
010402 general chemistry
Cleavage (embryo)
Animals
Humans
DNA Cleavage
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
Pharmacology
Nuclease
DNA ligase
MESH: Humans
010405 organic chemistry
Organic Chemistry
DNA
T4 DNA ligase assay
MESH: Crystallography
X-Ray
0104 chemical sciences
chemistry
Tin
Drug Design
biology.protein
Nucleic Acid Conformation
Cattle
Topoisomerase I Inhibitors
MESH: DNA Topoisomerases
Type I
Copper
Zdroj: European Journal of Medicinal Chemistry
European Journal of Medicinal Chemistry, 2012, 49, pp.141-50. ⟨10.1016/j.ejmech.2012.01.005⟩
European Journal of Medicinal Chemistry, Elsevier, 2012, 49, pp.141-50. ⟨10.1016/j.ejmech.2012.01.005⟩
ISSN: 0223-5234
1768-3254
DOI: 10.1016/j.ejmech.2012.01.005
Popis: International audience; A novel heterobimetallic Cu(II)-Sn(IV) complex 1 bearing bioactive 1,10-phenanthroline pharmacophore ligand scaffold was synthesized and characterized by elemental analysis, IR, UV-vis spectroscopy, Mass (ESI and FAB) and X-ray crystallography. The in vitro DNA binding studies of complex 1 with CT DNA was carried out by various biophysical and molecular docking techniques which revealed that complex 1 binds to DNA through intercalation in the minor groove having AT-rich sequences. Complex 1 exhibits high chemical nuclease activity cleaving supercoiled pBR322 DNA via hydrolytic pathway which was further evidenced by T4 DNA ligase assay. The complex 1 shows high inhibitory activity against Topo I at a very low concentration (15 μM), suggesting that complex 1 is an efficient catalytic inhibitor of human Topo I and further validated by molecular docking studies.
Databáze: OpenAIRE
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