TY - JOUR

T1 - Synthesis, DNA and BSA binding of Pd(II) and Pt(II) complexes featuring tetrazolylacetic acids and their esters

AU - Protas, Aleksandra V.

AU - Popova, Elena A.

AU - Mikolaichuk, Olga V.

AU - Porozov, Yu. B.

AU - Mehtiev, Arif R.

AU - Ott, Ingo

AU - Alekseev, G. V.

AU - Kasyanenko, Nina A.

AU - Trifonov, Rostislav E.

N1 - Funding Information: This work is supported by the Russian Science Foundation (grant 17-13-01124). We are very grateful to Tatiyana V. Serebryanskaya for useful discussions and help in the synthesis of compound 8 . Physicochemical measurements were carried out at the X-ray Diffraction Centre, the Centre for Magnetic Resonance, Centre for Molecular and Cell Technologies and the Centre for Chemical Analysis and Materials (all belong to Saint Petersburg State University). Appendix A

PY - 2018/3/24

Y1 - 2018/3/24

N2 - Two series of palladium(II) and platinum(II) complexes featuring esters of tetrazol-1-yl and tetrazol-5-ylacetic acids {trans-[PdCl 2L 2] and trans-[PtCl 2L 2], L = 5-methyl-1H-tetrazol-1-ylacetic acid and its ethyl, butyl, isobutyl esters (1–5); 2-R-2H-tetrazol-5-ylacetic acid and its ethyl esters, R = tBu, CH 2CH 2OH (6–10)} were synthesized and their binding to calf-thymus DNA (CT DNA) and bovine serum albumin (BSA) were studied by means of experimental (CD, UV, viscometry, fluorometric and electrophoretic techniques) and theoretical methods. According to the spectrophotometric data, the interaction of the metal complexes with CT DNA is observed. The significant increase of melting point of CT DNA in the presence of the metal complexes (ΔT m = 8–13 °C) indicates strong stabilization of the DNA helix. Electrophoretic studies demonstrate the ability of the metal complexes to interact with pBR322 plasmid DNA and to change its mobility. According to the data of the fluorescence quenching technique, binding with constants (K bin) of Pd(II) complexes with BSA are in the range 0.83–4.12 × 10 5 L M −1. The molecular docking studies show the minor groove binding behavior of tetrazole-containing palladium(II) and platinum(II) complexes to DNA (ΔG binding. −5.56 − −6.12 kcal/mol) and effective binding to BSA via the favored binding site Trp213 (ΔG binding −7.2 − −7.56 kcal/mol). The complex trans-[PtCl 2(2-tert-butyl-tetrazol-5-ylacetic acid) 2] exhibited noticeable antiproliferative activity in two human cancer cell lines with IC 50 values of 11.40 µM in HT-29 cells and 11.02 µM in MDA-MB-231 cell line.

AB - Two series of palladium(II) and platinum(II) complexes featuring esters of tetrazol-1-yl and tetrazol-5-ylacetic acids {trans-[PdCl 2L 2] and trans-[PtCl 2L 2], L = 5-methyl-1H-tetrazol-1-ylacetic acid and its ethyl, butyl, isobutyl esters (1–5); 2-R-2H-tetrazol-5-ylacetic acid and its ethyl esters, R = tBu, CH 2CH 2OH (6–10)} were synthesized and their binding to calf-thymus DNA (CT DNA) and bovine serum albumin (BSA) were studied by means of experimental (CD, UV, viscometry, fluorometric and electrophoretic techniques) and theoretical methods. According to the spectrophotometric data, the interaction of the metal complexes with CT DNA is observed. The significant increase of melting point of CT DNA in the presence of the metal complexes (ΔT m = 8–13 °C) indicates strong stabilization of the DNA helix. Electrophoretic studies demonstrate the ability of the metal complexes to interact with pBR322 plasmid DNA and to change its mobility. According to the data of the fluorescence quenching technique, binding with constants (K bin) of Pd(II) complexes with BSA are in the range 0.83–4.12 × 10 5 L M −1. The molecular docking studies show the minor groove binding behavior of tetrazole-containing palladium(II) and platinum(II) complexes to DNA (ΔG binding. −5.56 − −6.12 kcal/mol) and effective binding to BSA via the favored binding site Trp213 (ΔG binding −7.2 − −7.56 kcal/mol). The complex trans-[PtCl 2(2-tert-butyl-tetrazol-5-ylacetic acid) 2] exhibited noticeable antiproliferative activity in two human cancer cell lines with IC 50 values of 11.40 µM in HT-29 cells and 11.02 µM in MDA-MB-231 cell line.

KW - Anti-cancer activity

KW - Interaction with BSA/DNA

KW - Molecular docking

KW - Palladium(II) and platinum(II) complexes

KW - Tetrazolylacetic acids

KW - PLATINUM(II) COMPLEXES

KW - OXIME CHELATE LIGAND

KW - PROTEIN-BINDING

KW - 5-SUBSTITUTED NH-TETRAZOLES

KW - DNA/PROTEIN-BINDING

KW - MOLECULAR DOCKING

KW - COPPER(II) COMPLEXES

KW - BIOLOGICAL EVALUATION

KW - VITRO ANTICANCER ACTIVITY

KW - METAL-COMPLEXES

UR - http://www.scopus.com/inward/record.url?scp=85040243331&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/synthesis-dna-bsa-binding-pdii-ptii-complexes-featuring-tetrazolylacetic-acids-esters

U2 - 10.1016/j.ica.2017.12.040

DO - 10.1016/j.ica.2017.12.040

M3 - Article

VL - 473

SP - 133

EP - 144

JO - Inorganica Chimica Acta

JF - Inorganica Chimica Acta

SN - 0020-1693

ER -