DNA profiling and in vitro cytotoxicity studies of tetrazolo[1,5-a]pyrimidine-based copper(II) complexes

• Published in: Biometals 2019-08, Vol.32 (4), p.611-626
• Main Authors: Haleel, Azees Khan, Rafi, Ummer Muhammed, Mahendiran, Dharmasivam, Mitu, Liviu, Veena, Vijaykumar, Rahiman, Aziz Kalilur
• Format: Article
• Language: English
• Subjects: A549 Cells; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Aromatic compounds; Binding; Biochemistry; Biomedical and Life Sciences; Calf thymus; Cell Biology; Colon; Coordination compounds; Copper; Copper - chemistry; Copper compounds; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA fingerprinting; Electron paramagnetic resonance; Electrophoresis; Gel electrophoresis; Grooves; HeLa Cells; Humans; Leukocytes (mononuclear); Leukocytes, Mononuclear - cytology; Life Sciences; Lungs; Medicine/Public Health; Microbiology; Molecular docking; Molecular Docking Simulation; Peripheral blood mononuclear cells; Pharmacology/Toxicology; Plant Physiology; Plasmids; Pyrimidines - chemistry; Spectral methods; Toxicity
• ISSN: 0966-0844; 1572-8773
• DOI: 10.1007/s10534-019-00196-2

A series of N -benzoylated mononuclear copper(II) complexes of the type [Cu(L 1−6 )Cl 2 ] ( 1 – 6 ), where L 1 =  ethyl 4-benzoyl-5-methyl-7-aryl-4,7-dihydrotetrazolo[1,5- a ]pyrimidine-6-carboxylate, L 2 =  ethyl 4-(4-nitrobenzoyl)-5-methyl-7-aryl-4,7-dihydrotetrazolo[1,5- a ]pyrimidine-6-carboxylate, L 3  = ethyl 4-benzoyl-5-methyl-7-(4-methoxyphenyl)-4,7-dihydrotetrazolo[1,5- a ]pyrimidine-6-carboxylate, L 4  = ethyl 4-(4-nitrobenzoyl)-5-methyl-7-(4-methoxyphenyl)-4,7-dihydrotetrazolo[1,5- a ]pyrimidine-6-carboxylate, L 5  = ethyl 4-benzoyl-5-methyl-7-(4-chlorophenyl)-4,7-dihydrotetrazolo[1,5- a ]pyrimidine-6-carboxylate and L 6  = ethyl 4-(4-nitrobenzoyl)-5-methyl-7-(4-chlorophenyl)-4,7-dihydrotetrazolo[1,5- a ]pyrimidine-6-carboxylate have been synthesized and characterized by spectral methods. Electron paramagnetic resonance spectra of complexes show four lines, characteristic of square planar geometry. The binding studies of the complexes with calf thymus DNA (CT–DNA) revealed groove mode of binding, which were further supported by molecular docking studies. Gel electrophoresis experiments demonstrated the ability of the complexes to cleave plasmid DNA in the absence of activators. Further, the cytotoxicity activity of the complexes were examined on three cancerous cell lines (lung (A549), cervical (HeLa) and colon (HCT-15)), and on two normal cells (human embryonic kidney (HEK) and peripheral blood mononuclear cells (PBMC)) by MTT assay.