Novel 2‐formylpyridine 4‐allyl‐S‐methylisothiosemicarbazone and Zn(II), Cu(II), Ni(II) and Co(III) complexes: Synthesis, characterization, crystal structure, antioxidant, antimicrobial and antiproliferative activity

Abstract

New zinc (II), copper (II), nickel (II) and cobalt (III) complexes, [Zn (HL)2]I2 (1), [Cu (HL)Cl2] (2), [Cu (HL)Br2] (3), [Cu (HL)(H2O)2](ClO4)2 (4), [Ni (HL)2]I2·H2O (5), [Co(L)2]Cl (6), [Co(L)2]NO3 (7), [Co(L)2]I·[Co(L)2](I3) (8) were obtained with 2‐formylpyridine 4‐allyl‐S‐methylisothiosemicarbazone (HL). The isothiosemicarbazone ligand was characterized by NMR (1H and 13C), IR spectroscopy and X‐ray diffraction. All the complexes were characterized by elemental analysis, IR, UV–Vis, ESI‐MS spectroscopy, molar conductivity, magnetic susceptibility measurements. X‐ray diffraction analysis on the monocrystal and powder elucidated the structure of the complexes 1, 5, 7 and 8. The ligand and the complexes were tested for their antioxidant and antimicrobial activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Candida albicans. Also, the antiproliferative properties of these compounds on human leukemia HL‐60, human cervical epithelial HeLa, human epithelial pancreatic adenocarcinoma BxPC‐3, human muscle rhabdomyosarcoma spindle, large multinucleated RD cells and normal MDCK cells have been investigated. The nickel complex 5 and cobalt complexes 6, 7 showed promising antiproliferative activity and low toxicity.

Recent Studies on the Antimicrobial Activity of Transition Metal Complexes of Groups 6–12

“…According to the in vitro studies, cobalt(II)Pc and copper(II)Pc complexes, in particular, showed antibacterial activities against S. typhimurium and E. coli. Recently, a series of 2-formylpyridine 4-allyl-S-methylisothiosemicarbazone of zinc(II), copper(II), nickel(II) and cobalt(III) complexes were reported [110]. The in vitro tests showed that cobalt(III) complexes (43, Figure 9) were more active against Gram-positive bacteria (e.g., S. aureus) and fungal strains (C. albicans) with MIC values of 0.7-3 and 7-250 µg/mL, respectively, and less active against Gram-negative strains, such as E. coli and K. pneumoniae.…”

Synthesis, structural determination, in vitro and in silico biological evaluation of divalent or trivalent cobalt complexes with indomethacin

“…In 1952, the first reported studies regarding the biological activity of cobalt complexes examined the toxicity of the optical isomers of [Co(en) 3 ](NO 3 ) 3 (en = ethylenediamine) [ 3 ]. Since then, many cobalt complexes of biological interest have been reported with the majority of them showing antiproliferative [ [4] , [5] , [6] , [7] ], antimicrobial [ [8] , [9] , [10] ], antifungal [ 11 , 12 ], antiviral [ 13 , 14 ], and antioxidant [ [15] , [16] , [17] ] activity.…”

Synthesis, characterization, and biological activity of novel 3d metal coordination compounds with 2‐acetylpyridine N4‐allyl‐S‐methylisothiosemicarbazone

“…Unlike previously reported coordination compounds of 2‐formilpyridine N 4 ‐allyl‐ S ‐methylisothiosemicarbazone [ 24 ] and other 3 d metal coordination compounds with S ‐alkylisothiosemicarbazones, [ 35 ] it was proved that 2‐acetylpyridine N 4 ‐allyl‐ S ‐methylisothiosemicarbazone can act as tridentate ligand with NNN or NNS set of donor atoms. Previously, the coordination of S ‐alkylisothiosemicarbazones through alkylated sulfur atom was observed only in case of some palladium coordination compounds.…”

“…In the related neutral 2‐formylpyridine N 4 ‐allyl‐ S ‐methylisothiosemicarbazone, the nitrogen atoms of pyridine and hydrazine fragments are translocated. [ 24 ] The iodine and nonhydrogen atoms of H 2 L except C 3 H 5 substituent in A and B are coplanar within 0.1 Å. In the crystal of polymorphs, the [H 2 L]I units form stack with antiparallel arrangement of organic molecules in A and about parallel in B .…”

“…Recently, we have published works describing the synthesis, structure, physicochemical, and biological properties of 2‐hydroxybenzaldehyde and 2‐formylpyridine N 4 ‐allyl‐ S ‐methylisothiosemicarabzones. [ 23,24 ] It was found that these isothiosemicarbazones and 3 d metal coordination compounds with them manifest antiproliferative activity against HeLa, BxPC‐3, and RD cancer cell lines. Among the described substances, the copper(II) and nickel(II) coordination compounds possess the lowest values of inhibitory concentrations (IC 50 = 0.36 ÷ 54 μM).…”