TY - JOUR

T1 - Synthesis, biological evaluation and molecular docking studies on the DNA and BSA binding interactions of palladium(II) and platinum(II) complexes featuring amides of tetrazol-1-yl- and tetrazol-5-ylacetic acids

AU - Popova, Elena A.

AU - Protas, Aleksandra V.

AU - Mukhametshina, Anastasiya V.

AU - Ovsepyan, Gayane K.

AU - Suezov, Roman V.

AU - Eremin, Alexei V.

AU - Stepchenkova, Elena I.

AU - Tarakhovskaya, Elena R.

AU - Fonin, Alexander V.

AU - Starova, Galina L.

AU - Mikolaichuk, Olga V.

AU - Porozov, Yuri B.

AU - Gureev, Maksim A.

AU - Trifonov, Rostislav E.

N1 - Funding Information: This work is supported by the Russian Science Foundation (grant 17-13-01124 ). Physicochemical measurements were carried out at the X-ray Diffraction Centre, the Centre for Magnetic Resonance and the Centre for Chemical Analysis and Materials (all belong to Saint Petersburg State University). Publisher Copyright: © 2018 Elsevier Ltd Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019/1/15

Y1 - 2019/1/15

N2 - Novel palladium(II) and platinum(II) complexes (trans-[PdCl2L2] and trans-[PtCl2L2] {L = 2-(5-methyl-1H-tetrazol-1-yl)acetamide, N-(sec-butyl)-2-(5-methyl-1H-tetrazol-1-yl)acetamide, N-cyclopropyl-2-(5-methyl-1H-tetrazol-1-yl)acetamide, N-cyclohexyl-2-(5-methyl-1H-tetrazol-1-yl)acetamide, 2-(2-(tert-butyl)-2H-tetrazol-5-yl)acetamide and 2-(2-(tert-butyl)-2H-tetrazol-5-yl)-N-cyclohexylacetamide} 1b–6b and 1c–4c) were synthesized and characterized by elemental analyses (CHN), HRESI+-MS, 1H, 13C{1H}, 195Pt NMR and IR spectroscopies, DSC/TG analysis, as well as by X-ray single crystal diffraction {for (2-(5-methyl-1H-tetrazol-1-yl)acetamide) 1a·H2O, trans-[PdCl2(2-(5-methyl-1H-tetrazol-1-yl)acetamide)2] 1b, trans-[PdCl2(N-cyclopropyl-2-(5-methyl-1H-tetrazol-1-yl)acetamide)2] 3b and trans-[PdCl2(N-cyclohexyl-2-(5-methyl-1H-tetrazol-1-yl)acetamide)2] 4b}. The binding of complexes 2b and 5b to calf-thymus DNA (CT DNA) and BSA (bovine serum albumin) was studied by means of CD, UV and fluorometric techniques. According to the spectroscopic data, an interaction of the metal complexes with CT DNA was confirmed. A significant increase in the melting point of CT DNA in the presence of the metal complexes {ΔTm = 10.0 °C (for 2b), 12.5 °C (for 5b)} indicates a strong stabilization of the DNA helix. According to the fluorometric data, complex 2b exhibits an interaction with BSA. Additionally, molecular docking results suggest that complex 1b and its fully hydrolyzed form (trans-[Pd(H2O)2(2-(5-methyl-1H-tetrazol-1-yl)acetamide)2]) cooperatively interact with DNA, presumably via minor groove binding. The hydrolyzed form possesses a greater affinity to DNA. Also, there is an effective interaction of complex 1b and the corresponding hydrolyzed form to BSA via the two binding sites Trp134 and Trp213. Two complexes {trans-[PdCl2(N-(sec-butyl)-2-(5-methyl-1H-tetrazol-1-yl)acetamide)2] 2b and trans-[PdCl2(2-(2-(tert-butyl)-2H-tetrazol-5-yl)acetamide)2] 5b} demonstrate antiproliferative activity against human cancer cell lines, with IC50 = 45 ± 0.5 µM for 2b on HeLa and IC50 = 44.3 ± 0.8 µM for 5b on MCF-7. The complexes 4b, 4c and 6b were evaluated for their antimicrobial activity against Escherichia coli (strain КA796) and they showed significant activities, being greater than that of cisplatin. Complex 4b was the most effective, with the lowest MLC value of 0.25 µM and LC50 value of 0.075 µM.

AB - Novel palladium(II) and platinum(II) complexes (trans-[PdCl2L2] and trans-[PtCl2L2] {L = 2-(5-methyl-1H-tetrazol-1-yl)acetamide, N-(sec-butyl)-2-(5-methyl-1H-tetrazol-1-yl)acetamide, N-cyclopropyl-2-(5-methyl-1H-tetrazol-1-yl)acetamide, N-cyclohexyl-2-(5-methyl-1H-tetrazol-1-yl)acetamide, 2-(2-(tert-butyl)-2H-tetrazol-5-yl)acetamide and 2-(2-(tert-butyl)-2H-tetrazol-5-yl)-N-cyclohexylacetamide} 1b–6b and 1c–4c) were synthesized and characterized by elemental analyses (CHN), HRESI+-MS, 1H, 13C{1H}, 195Pt NMR and IR spectroscopies, DSC/TG analysis, as well as by X-ray single crystal diffraction {for (2-(5-methyl-1H-tetrazol-1-yl)acetamide) 1a·H2O, trans-[PdCl2(2-(5-methyl-1H-tetrazol-1-yl)acetamide)2] 1b, trans-[PdCl2(N-cyclopropyl-2-(5-methyl-1H-tetrazol-1-yl)acetamide)2] 3b and trans-[PdCl2(N-cyclohexyl-2-(5-methyl-1H-tetrazol-1-yl)acetamide)2] 4b}. The binding of complexes 2b and 5b to calf-thymus DNA (CT DNA) and BSA (bovine serum albumin) was studied by means of CD, UV and fluorometric techniques. According to the spectroscopic data, an interaction of the metal complexes with CT DNA was confirmed. A significant increase in the melting point of CT DNA in the presence of the metal complexes {ΔTm = 10.0 °C (for 2b), 12.5 °C (for 5b)} indicates a strong stabilization of the DNA helix. According to the fluorometric data, complex 2b exhibits an interaction with BSA. Additionally, molecular docking results suggest that complex 1b and its fully hydrolyzed form (trans-[Pd(H2O)2(2-(5-methyl-1H-tetrazol-1-yl)acetamide)2]) cooperatively interact with DNA, presumably via minor groove binding. The hydrolyzed form possesses a greater affinity to DNA. Also, there is an effective interaction of complex 1b and the corresponding hydrolyzed form to BSA via the two binding sites Trp134 and Trp213. Two complexes {trans-[PdCl2(N-(sec-butyl)-2-(5-methyl-1H-tetrazol-1-yl)acetamide)2] 2b and trans-[PdCl2(2-(2-(tert-butyl)-2H-tetrazol-5-yl)acetamide)2] 5b} demonstrate antiproliferative activity against human cancer cell lines, with IC50 = 45 ± 0.5 µM for 2b on HeLa and IC50 = 44.3 ± 0.8 µM for 5b on MCF-7. The complexes 4b, 4c and 6b were evaluated for their antimicrobial activity against Escherichia coli (strain КA796) and they showed significant activities, being greater than that of cisplatin. Complex 4b was the most effective, with the lowest MLC value of 0.25 µM and LC50 value of 0.075 µM.

KW - Anti-cancer and antimicrobial activities

KW - Interaction with BSA/DNA

KW - Molecular docking

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

KW - Tetrazolylacetamides

UR - http://www.scopus.com/inward/record.url?scp=85056222139&partnerID=8YFLogxK

U2 - 10.1016/j.poly.2018.10.038

DO - 10.1016/j.poly.2018.10.038

M3 - Article

AN - SCOPUS:85056222139

VL - 158

SP - 36

EP - 46

JO - Polyhedron

JF - Polyhedron

SN - 0277-5387

ER -