Synthesis,characterization and in vitro cytotoxicity of palladium(II) complexes with mixed ligands. X‐ray diffraction study of C31H36ClNPPdS2

Pd(II) complexes with organophosphines and dithiocarbamates derivatives of α‐amino acids were synthesized by reacting N,N‐dicyclohexyldithiocarbamate (DCHDTC, compounds 1 – 3 ) and N‐methylcyclohexyldithiocarbamate (MCHDTC, compounds 4 – 6 ) with (R₃P)₂PdCl₂ (R = Ph, o‐tolyl, Ph₂Cl) in a 1:1 molar ratio. The complexes were characterized by elemental analyses, FT‐IR, multinuclear (¹H, ¹³C and ³¹P) NMR and single X‐ray crystallography, showing that the dithiocarbamate acts as a bidentate ligand and binds to Pd(II) via two sulfur atoms, resulting in a square planar geometry around Pd(II). The cytotoxicity of compounds 2, 3 and 4 was determined in vitro against six human tumour cell lines, MCF7, EVSA‐T, WIDR, IGROV, M19 MEL, A498 and H226. Compounds 3 and 4 showed a moderate to low cytotoxicity, whereas compound 2 exhibited a very low cytotoxicity. The results of antifungal assays showed that compounds 1 – 6 possess antifungal activity against Fusarium moniliformes, Fusarium saolani, Mucor sp., Aspergillus niger and Aspergillus fumigatus. The anti‐inflammatory screening results of 1–6 are quite similar to those observed for the standard drug Declofenac at 10 mg kg^?1, which inhibited the odema by 74% after 4 h. Copyright © 2007 John Wiley & Sons, Ltd.     

Synthesis,structure, characterization and biological evaluation of 3‐substituted 1‐pyridin‐2‐ylimidazo[1,5‐a]pyridine‐based copper(I)–phosphine complexes for anticancer drug screening

Copper(I) complexes of the types [Cu(N–N)(PPh₃)₂]NO₃ (LC41–LC44) and [Cu(N–N)(PPh₃)(NO₃)] (LC45) carrying 3‐substituted 1‐pyridine‐2‐ylimidazo[1,5‐a]pyridine (N–N) derivatives and triphenylphosphine (PPh₃) ligands have been prepared. The synthesized copper(I)–phosphine complexes were fully characterized by NMR, IR, ESI‐MS and UV–visible spectroscopy as well as by cyclic voltammetry. Selected structures such as LC42, LC43 and LC45 were additionally analysed by single‐crystal X‐ray method, which show that copper(I) centre adopts a highly distorted tetrahedral geometry. The ¹H and ¹³C NMR spectral data of the complexes throw light on the nature of metal–ligand bonding. They display dπ–π* metal‐to‐ligand charge transfer (MLCT) transition and show quasireversible Cu^I/Cu^II metal oxidation. Among the copper(I)–phosphine complexes, LC41–LC44 exhibit moderate cytotoxicity (IC₅₀: 24 h, 67–74 μM; 48 h, 58–70 μM) against human lung epithelial adenocarcinoma A549 cells, whereas LC45 displays the best activity (IC₅₀: 24 h, 42 μM; 48 h, 34 μM) for A549 cancer cell line, which is better than that of the commercial antitumor drug cisplatin. All the complexes also displayed excellent selectivity by being relatively inactive against the human lung epithelial L132 normal cell line with selectivity index (SI) values ranging from 3.4 to 7.4. The complexes block cell cycle progression of A549 cells in G₀/G₁ phase. FACSVerse analyses are suggestive of reactive oxygen species (ROS) generation and apoptotic cell death induced by the LC41, LC43 and LC45. The induction of apoptosis in A549 cells was shown by Annexin V with propidium iodide (PI) and 4′,6‐diamidino‐2‐phenylindole (DAPI) staining methods and established the ability of LC41, LC43 and LC45 to accumulate in the cell nuclei.     

Aryl Phosphine Nickel(II) and Palladium(II) Complexes with N,O‐Amino‐carboxylate Chelate Ligands [(Aryl)(R3P)M(N,O‐α‐aminocarboxylate)](M = Ni,Pd). Catalysts for the Polymerization of Olefins

The title complexes [(Aryl)(R₃P)M(N,O‐α‐aminocarboxylate)] (M = Ni, Pd) were synthesized by reaction of [(o‐tolyl)(Ph₃P)₂NiBr] or of [(p‐Me₃CC₆H₄)(o‐tolyl₃P)Pd(μ‐Br)]₂ with the anions of α‐amino acids. The spectroscopic data indicate that the nickel complexes are formed as mixtures of isomers, whereas for the palladium complexes only one isomer is observed. The complex [(o‐tolyl)(Ph₃P)Ni(glycinate)] is – in the presence of AlEt₃ – a highly active catalyst for the polymerization of ethylene [up to 1800 kg PE / (mol Ni·h)] and gives polymers with remarkably high molecular weights (up to 900.000 g/mol) and with few branchings.     

一种经(E)-α-碘代烯基砜的钯催化交叉偶联反应立体选择合成(1Z,3E)-2-芳砜基取代的1,3-二烯的新方法

（E）-α-Stannylvinyl phenyl（or p-tolyl）sulfones underwent an iododestannylation reaction to afford （E）-α-iodovinyl phenyl（or p-tolyl）sulfones 1, which reacted with （E）-alkenylzirconium（IV） complexes 2 produced in situ by hydrozirconation of terminal alkynes in the presence of a Pd（PPh3）4 catalyst to afford stereoselectively （1Z,3E）-2- phenyl（or p-tolyl）sulfonyl-substituted 1,3-dienes 3 in good yields.     

Investigation of Suzuki–Miyaura catalyst‐transfer polycondensation of AB‐type fluorene monomer using coordination‐saturated aryl Pd(II) halide complexes as initiators

Novel triarylamine‐based coordination‐saturated aryl Pd(II) halide complexes ligated by PEt₃, PCy₃, and P(o‐tol)₃ were successfully synthesized by direct oxidative addition of aryl halide to the corresponding Pd(0) precursors. Suzuki–Miyaura coupling polymerization of 2‐(7‐halide‐9,9‐dioctylfluoren‐2‐yl)?1,3,2‐dioxaborinane with these Pd(II) complexes as initiators was investigated for the synthesis of poly(fluorene)s with triarylamine end group. Pd(II) complexes with PCy₃ or P(o‐tol)₃ exhibited catalytic activity and realized the catalyst‐transfer polycondensation at 75 °C and room temperature, respectively, while the polymerization using Pd(II) catalyst ligated by PEt₃ did not proceed, which indicated that the bulky phosphine ligands could facilitate the reductive elimination and further promote the polymerization. In addition, the dimeric Pd(II) complex with P(o‐tol)₃ can convert into monomeric Pd(II) intermediate with an open coordination site, which had a higher activity. The end groups of the afforded polyfluorene were analyzed by matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) mass spectrometry, in which the Ar/H end groups are indicative of the catalyst‐transfer polymerization. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1457–1463     

Synthesis,Characterization, and in vitro Cytotoxicity of Gold(I) Complexes of 2‐(Diphenylphosphanyl)ethylamine and Dithiocarbamates

Gold(I) complexes of 2‐(diphenylphosphanyl)ethylamine or (2‐aminoethyl)diphenylphosphine (AEP), and dithiocaarbamates (R₂NCS₂) were prepared by the reaction of these ligands with (CH₃)₂S‐AuCl in dichloromethane. The synthesized complexes [Au(AEP)Cl] ( 1 ), [Au(AEP)₂]Cl ( 2 ), and [Au₂(R₂NCS₂)₂]_n (R₂ = dimethyl ( 3 ), diethyl ( 4 ), and dibenzyl ( 5 )) were characterized by elemental analysis, IR, ¹H, ¹³C and ³¹P NMR spectroscopy. The complexes were evaluated for anticancer activity against three cancer cells, A549 (human lung carcinoma), HCT15 (human colon cancer), and MCF7 (human breast cancer) cell lines. Three of the five tested complexes showed significant in vitro cytotoxicity and for A549, the inhibition effect of three compounds is greater than cisplatin.     

Evaluation of ruthenium‐based catalytic systems for the controlled atom transfer radical polymerisation of vinyl monomers

Only [RuCl₂(p‐cymene)(PR₃)] complexes where the phosphine ligand, PR₃, is both strongly basic and bulky proved to be effective catalysts for the controlled atom transfer radical polymerisation (ATRP) of methyl methacrylate and styrene. The best phosphine ligands were typically P(i‐Pr)₃, P(cyclohexyl)₂Ph, P(cyclohexyl)₃, and P(cyclopentyl)₃. Less basic and/or bulky phosphines led to ineffective systems for ATRP. Tricyclohexylarsine gave rise to a highly efficient catalyst system. However, related complexes in which the phosphine ligand was replaced by tricyclohexylstibine, nitrogen (piperidine and 4‐cyanopyridine) and carbon ligands (alkyl isocyanides) proved to be inefficient. The observation of a direct relationship between the p‐cymene lability (measured by TGA) and catalyst activity suggests that p‐cymene release is a prerequisite for the polymerisation process.     

Anticancer metallopharmaceutical agents based on mixed‐ligand palladium(II) complexes with dithiocarbamates and tertiary organophosphine ligands

Mixed‐ligand palladium(II) complexes of the type [(DT)Pd(PR₃)Cl], where DT = diethyldithiocarbamate (1), dibutyldithiocarbamate (2,3), dipropyldithiocarbamate (4,5), bis(2‐methoxyethyl)dithiocarbamate; PR₃ = benzyldiphenylphosphine (1,4), diphenyl‐o‐tolylphosphine (2), diphenyl‐t‐butylphosphine (3), P‐chlorodiphenylphosphine (5) and triphenylphosphine (6), have been synthesized and characterized by elemental analyses and FT‐IR, Raman and multinuclear NMR spectroscopy. The structures of compounds 1 and 2 were determined by single‐crystal X‐ray diffraction (XRD) measurements and these analyses showed that the complexes have pseudo square‐planar geometry around the Pd(II) and that the dithiocarbamate ligand is bound in a bidentate fashion, while the remaining two positions are occupied by a tertiary organophosphine and a chloride ligand. The anticancer studies showed that the Pd(II) complexes are highly active against cisplatin‐resistant DU145 human prostate carcinoma (HTB‐81) cells with the highest activity shown by compound 6 (IC₅₀ = 2.12 µm ). The redox behavior and ds‐DNA‐denaturing ability of the complexes were studied by cyclic voltammetry and two reduction and one oxidation waves were observed. The decrease in the reduction peak currents illustrated the consumption of the mixed‐ligand drug by the DNA molecule. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis and Cytotoxicity of Arene‐Ru Compounds Containing 4‐Nitroaniline or 2‐Halogenated 4‐Nitroaniline

The compounds [(η⁶‐p‐cymene)RuCl₂(4‐nitroaniline)] and [(η⁶‐p‐cymene)RuCl₂(2‐halogen‐4‐nitroaniline)] were synthesized and characterized by various means. The [(η⁶‐p‐cymene)RuCl₂(4‐nitroaniline)] and [(η⁶‐p‐cymene)RuCl₂(2‐fluoro‐4‐nitroaniline)] compounds were determined by X‐ray diffraction, appearing in a distorted piano‐stool type of arrangement with similar bond lengths and angles around the ruthenium. The compounds exhibited moderate to strong in vitro cytotoxicity against A549 and MCF‐7 human cancer cells. Substitution of heavy halogen atom on the ortho position of para‐nitroaniline weakened the cytotoxicity against both of MCF‐7 and A549, except the cases of fluorine substitution for hydrogen atom regarding A549 and bromine substitution for chlorine atom regarding MCF‐7, which showed minor deviation.     

In vitro anti‐proliferative and in silico docking studies of heteroleptic copper(II) complexes of pyridazine‐based ligands and ciprofloxacin

Three heteroleptic copper(II) complexes of the type [Cu(L^1–3)(cf)(ClO₄)] ( 1 – 3 ), where cf = ciprofloxacin, have been synthesized using pyridazine‐based ligands 3‐chloro‐6‐(salicylidenehydrazinyl)pyridazine (HL¹), 3‐chloro‐6‐(4‐diethylaminosalicylidenehydrazinyl)pyridazine (HL²) and 3‐chloro‐6‐(5‐bromosalicylidenehydrazinyl)pyridazine (HL³). Electronic spectral data and magnetic moment values suggest octahedral geometry for the synthesized copper(II) complexes. Electrochemical data of the copper(II) complexes present an irreversible one‐electron reduction wave in the cathodic potential region (E_pc) between ?0.631 and ?0.670 V. Frontier molecular orbital calculations were carried out, and the obtained low‐energy gap supports the bio‐efficacy of the complexes. All the complexes were screened for their in vitro cytotoxicity activity against three human cancerous (breast adenocarcinoma (MCF‐7), hepatoma (HepG‐2) and cervical (HeLa)) and one non‐cancerous (non‐tumorigenic human dermal fibroblast (NHDF)) cell lines using MTT assay, in which complex 2 exhibited higher activity. The apoptosis induction by the complexes was analysed using the Hoechst dye staining method with MCF‐7 cell line, which indicates higher apoptotic activity of complex 2 . A molecular docking study was carried out to ascertain the binding affinity of the synthesized heteroleptic copper(II) complexes with phosphoinositide 3‐kinase gamma (PI3Kγ) receptor.     

ONO pincer‐type palladium(II) complexes of heterocyclic hydrazone: Synthesis,characterization and biological evaluation

Two new Pd(II) complexes of N′‐(4‐(diethylamino)‐2‐hydroxybenzylidene)furan‐2‐carbohydrazide were synthesized and characterized using various spectral methods. The structure of one of the complexes was determined using single‐crystal X‐ray diffraction. DNA and protein binding affinities of the synthesized compounds were examined using UV–visible and fluorescence titration method. In addition, the in vitro cytotoxicity of the compounds was evaluated against A549 (lung cancer) and MCF7 (breast cancer) cell lines using the MTT assay method.     

Synthesis,characterization and in vitro cytotoxicity of homobimetallic complexes of palladium(II) with 2‐thiouracil ligands. Crystal structure of [Pd2(TU)(PPh3)3Cl2]

Square planar metallic and homonuclear bimetallic complexes of Pd(II) with 2‐thiouracil (HTU) and organophosphines have been synthesized and characterized by FT‐IR and multinuclear ¹H, ¹³C, ³¹P NMR spectroscopy. The thiouracil ligand TU acts as bidentate, is bound through the thioxo moiety and the endo amino group and forms a bridge between a PdCl(R₃P) and a PdCl(R₃P)₂ moiety [R₃P = Ph₃P (o‐tolyl)₃P, ClPh₂P] in the homonuclear bimetallic complexes. The square planar geometry around Pd(II) has been confirmed for these complexes by a single‐crystal X‐ray diffraction study of compound 1 , [Pd₂(TU)(PPh₃)₃Cl₂]. These compounds were also screened against human tumor cell lines and showed promising in vitro cytotoxicity. Copyright © 2007 John Wiley & Sons, Ltd.     

Methyl substituent effect on one‐dimensional copper(II) coordination polymers containing biologically active ligands: Synthesis,characterization, DNA interactions and cytotoxicities

Three novel water‐soluble copper(II) complexes – {[Cu(phen)(trp)]ClO₄·3H₂O}_n ( 1 ), {[Cu(4‐mphen)(trp)]ClO₄·3H₂O}_n ( 2 ) and [[Cu(dmphen)(trp)(MeOH)][Cu(dmphen)(trp)(NO₃)]]NO₃ ( 3 ) (phen: 1,10‐phenanthroline; 4‐mphen: 4‐methyl‐1,10‐phenanthroline; dmphen: 4,7‐dimethyl‐1,10‐phenanthroline; trp: l ‐tryptophan) – have been synthesized and characterized using various techniques. Complexes 1 and 2 are isostructural, and exist as one‐dimensional coordination polymers. Complex 3 consists of two discrete copper(II) complexes containing [Cu(trp)(dmphen)(MeOH)]⁺, [Cu(trp)(dmphen)(NO₃)] and one nitrate anion. The binding interaction of the complexes with calf thymus DNA (CT‐DNA) was investigated using thermal denaturation, electronic absorption and emission spectroscopic methods, revealing that the complexes could interact with CT‐DNA via a moderate intercalation mode. The binding activity of the complexes to CT‐DNA follows the order: 3  >  2 > 1 . The pUC19 DNA cleavage activity of the complexes was investigated in the absence and presence of external agents using the agarose gel electrophoresis method. Especially, in the presence of H₂O₂ as an activator, the pUC19 DNA cleavage abilities of the complexes are clearly enhanced at low concentration. Addition of hydroxyl radical scavenger dimethylsulfoxide shows a marked inhibition of the pUC19 DNA cleavage activity of the complexes. In vitro cytotoxic effect of the complexes was examined on human tumor cell lines (Caco‐2, A549 and MCF‐7) and healthy cells (BEAS‐2B). The potent cytotoxic effect of complex 3 , with IC₅₀ values of 1.04, 1.16 and 1.72 μM, respectively, is greater relative to clinically used cisplatin (IC₅₀ = 22.70, 31.1 and 22.2 μM) against the Caco‐2, A549 and MCF‐7 cell lines.     

Biological evaluation of organometallic palladium(II) complexes containing 4‐hydroxybenzoic acid (3‐ethoxy‐2‐hydroxybenzylidene)hydrazide: Synthesis,structure, DNA/protein binding,antioxidant activity and cytotoxicity

New palladium(II) complexes, [Pd(PPh₃)L] ( 2 ) and [Pd(AsPh₃)L] ( 3 ), were synthesized using 4‐hydroxybenzoic acid (3‐ethoxy‐2‐hydroxybenzylidene)hydrazide ( 1 ) ligand (H₂L), and characterized using various physicochemical techniques. The molecular structures of 2 and 3 were determined using single‐crystal X‐ray diffraction, which reveals a square planar geometry around the palladium(II) metal ion. In vitro DNA binding studies were conducted using UV–visible absorption spectroscopy, emission spectroscopy, cyclic voltammetry and viscosity measurements, which suggest that the metal complexes act as efficient DNA binders. The interaction of ligand H₂L and complexes 2 and 3 with bovine serum albumin (BSA) was investigated using UV–visible and fluorescence spectroscopies. Absorption and emission spectral studies indicate that complexes 2 and 3 interact with BSA protein more strongly than the parent ligand. The free radical scavenging potential of all the synthesised compounds ( 1 – 3 ) was also investigated under in vitro conditions. In addition, the in vitro cytotoxicity of the complexes to tumour cells lines (HeLa and MCF‐7) was examined using the MTT assay method.     

Three Arene‐Ru(II) compounds of 2‐halogen‐5‐aminopyridine: Synthesis,characterization, and cytotoxicity

Three novel compounds, (η⁶‐p‐cymene)RuCl₂(2‐fluoro‐5‐aminopyridine) (compound 1), (η⁶‐p‐cymene)RuCl₂(5‐amino‐2‐chlorpyridine) (compound 2) and (η⁶‐p‐cymene)RuCl₂(2‐bromo‐ 5‐aminopyridine) (compound 3), were synthesized and characterized. The compound 1 and 3 were determined by X‐ray diffraction, showing a distorted piano‐stool type of geometry with similar bond lengths and angles around the ruthenium. Compound 2 exhibited moderate in vitro activity against A549 and MCF‐7 human cancer cells, the other two lower activities. The UV–vis and fluorescent absorption titrations showed that three compounds binded with CT‐DNA in a minor groove. The intrinsic binding constants (Kb) were calculated to be 2.13(±0.03) × 10⁵ M^?1, 2.89(±0.03) × 10⁵ M^?1 and 2.45(±0.03) × 10⁵ M^?1 for compound 1, 2 and 3, respectively, by using UV–vis absorption titrations data. Among the three compound, the highest value of intrinsic binding constant of compound 2 was consistent with its highest cytoxicity against A549 and MCF‐7 human cancer cells in vitro.     

Mononuclear palladacycles of N,N′-diaryl-2-iminoisoindolines

Reaction of acetato-bridged dinuclear palladacycles, [Pd(iminoisoindoline)(μ-OAc)]₂, with stoichiometric amounts of PR₃ (where R = Ph or Cy) resulted in formation of the corresponding mononuclear phosphine-ligated, six-membered palladacycles with the general formula [Pd(iminoisoindoline)(OAc)PR₃]. The analogous chloride complexes were synthesized by reaction of [Pd(iminoisoindoline)(μ-OAc)]₂ with LiCl in acetone followed by addition of phosphine to afford the monomeric derivatives [Pd(iminoisoindoline)(Cl)PR₃]. Representative crystal structures of both types of mononuclear palladacycles confirmed the mononuclear nature of the complexes and showed a trans-arrangement of the phosphine ligand to the heterocyclic imine-nitrogen of the palladacycles.     

THEORETICAL INVESTIGATION OF KETENE BONDING MODES IN BIS(PHOSPHINE) PALLADIUM KETENE COMPLEXES

Abstract

Theoretical studies were carried out on a series of bis(phosphine) palladium ketene complexes (PR₃)₂Pd(CH₂=C=O), and on the related CH₂=C=O and Pd(PR₃)₂ molecular fragments in order to investigate the electronic structure and the bonding of the ketene ligand to the metal fragment in these complexes. An analysis of the frontier MOs has been performed in order to understand the interactions between the ketene and the metal fragments. The calculated results have shown that the η²-(C,C) mode is preferred over the η²-(C,O) mode by 10–15 kcal/mol in bis(phosphine) palladium ketene complexes. The basicity and bulkiness of the phosphine ligands PR₃ have little effect on the bonding mode in (PR₃)₂Pd(CH₂=C=O) complexes. The most stable structure was calculated to be the η²-(C,C) square planar geometry with the CH₂ group of ketene out of the molecular plane. Comparison and discussion between the two bonding modes were also presented in this paper.     

Highly Cytotoxic Bioconjugated Gold(I) Complexes with Cysteine‐Containing Dipeptides

Several gold(I) complexes with cysteine‐containing dipeptides have been prepared starting from cystine by coupling different amino acids and using several orthogonal protections. The first step is the reaction of cystine, where the sulfur centre is protected as disulfide, with Boc₂O in order to protect the amino group, followed by coupling of an amino acid ester; finally the disulfide bridge is broken with mercaptoethanol to afford the dipeptide derivative. Further reaction with [AuCl(PPh₃)] gives the gold‐dipeptide‐phosphine species. Starting from these formally gold(I) thiolate–dipeptide phosphine complexes with the general formula [Au(SR)(PR₃)] different structural modifications, such as change in the type of the amino protecting group, the type of phosphine, the number of gold(I) atoms per molecule, or the use of a non‐proteinogenic conformationally restricted amino acid ester, were introduced in order to evaluate their influence in the biological activity of the final complexes. The cytotoxic activity, in vitro, of these complexes was evaluated against different tumour human cell lines (A549, MiaPaca2 and Jurkat). The complexes show an outstanding cytotoxic activity with IC₅₀ values in the very low micromolar range. Structure–activity relationship studies from the complexes open the possibility of designing more potent and promising gold(I) anticancer agents.     

Robust and Electron‐Rich cis‐Palladium(II) Complexes with Phosphine and Carbene Ligands as Catalytic Precursors in Suzuki Coupling Reactions

A new imidazolinium ligand precursor [L²H]Cl ( 2 ) was prepared in 86 % yield. Compared with its imidazolium counterpart, [L¹H]Cl ( 1 ), 2 is very sensitive to moisture and can undergo ring‐opening reactions very readily. Palladium complexes with the ring‐opened products from imidazolinium salts were isolated and characterized by X‐ray crystallography. Theoretical studies confirmed that the imidazolinium salt has a higher propensity for the ring‐opening reaction than the imidazolium counterpart. New mixed phosphine/carbene palladium complexes, cis‐[PdCl₂(L)(PR₃)] (L=L¹ and L²; R=Ph, Cy), were successfully prepared. These complexes are highly robust as revealed by variable‐temperature NMR spectroscopic studies and thermal gravimetric analysis. The structural and electronic properties of the new complexes on varying the carbene group (imidazol‐2‐ylidene group (unsaturated carbene) vs. imidazolin‐2‐ylidene (saturated carbene)) and the phosphine group (PPh₃ vs. PCy₃) were studied in detail by X‐ray crystallography, X‐ray photoelectron spectroscopy, and theoretical calculations. The catalytic study reveals that cis‐[PdCl₂(L²)(PCy₃)] is a competent Pd^II precatalyst for Suzuki coupling reactions, in which unreactive aryl chlorides can be applied as substrates.     

Synthesis,spectroscopic characterization,biological screening and in vitro cytotoxic studies of 4‐methyl‐3‐thiosemicarbazone derived Schiff bases and their Co (II), Ni (II), Cu (II) and Zn (II) complexes

A series of twenty compounds inclusive of bidentate Schiff bases derived from condensation of 4‐methyl‐3‐thiosemicarbazide with substituted derivatives of napthaldehyde/benzaldehyde/salicylaldehyde and their mononuclear Co (II), Ni (II), Cu (II) and Zn (II) complexes in molar ratio (1:1) were synthesized and characterized. The coordination behavior, modes of bonding and overall geometry of the compounds was known from the elemental analysis, spectral techniques (IR, UV–Vis, ¹H NMR, ¹³C NMR, ESR and ESI‐mass), magnetic moment measurements, molar conductance, thermal and powder XRD studies. The studies revealed octahedral geometry for all the complexes where ligands coordinated in a neutral bidentate manner (NS) via nitrogen atom of azomethine group and sulphur atom of thione group with the metal centre. In vitro biological effects of the compounds were tested against four bacterial species and two fungal strains. The results indicated that the metal complexes showed a marked enhancement in biocidal activity in comparable with the parent Schiff bases. In vitro anticancer activity against the malignant tumor cell lines; human alveolar adenocarcinoma epithelial cell line (A549), human breast adenocarcinoma cell line (MCF7), human prostate cancer cell line (DU145) and human normal lung cell line (MRC‐5) using MTT assay, exposed compound 16 as a leading member with lowest IC₅₀ value of 10.6 ± 0.14 μM against (A549) cell line.