Benzoyl Thiourea Research Articles

Design of novel copper(I) metallomesogens with benzoylthiourea ligands having peripherally connected cyano or fluoro groups

A new set of liquid crystals based on copper(I) complexes with a cyano or fluoro group attached at the para position of an aromatic ring in a benzoyl thiourea ligand was prepared and studied for their liquid crystalline properties. Incorporating electron-withdrawing fluoro or cyano groups into the structural matrix can enhance their thermal stability, phase transition temperatures, and optical properties. The prepared Cu(Ln)2X compounds, where X = Cl, Br, or I, and 4-(dodecyloxy)-N-((4-fluorophenyl)carbamothioyl)benzamide (L1), N-((4-cyanophenyl)carbamothioyl)-4-(dodecyloxy)benzamide (L2), N-((4-fluorophenyl)carbamothioyl)-3,4-bis(octyloxy)benzamide (L3), and N-((4-cyanophenyl)carbamothioyl)-3,4-bis(octyloxy)benzamide (L4) displayed a SmA mesophase depending on the type of the attached terminal group (F or CN), number of alkoxy chains (one or two) and the nature of the halide ion coordinated to the metal center (Cl, Br or I). The structures of the compounds were characterized by 1H and 13C NMR, ESI-MS and IR studies, and their mesomorphic properties were investigated via a combination of polarising optical microscopy (POM), differential scanning calorimetry (DSC), and powder X-ray diffraction studies. These compounds were stable throughout the temperature range of the mesophases. This study further reiterates the consequential effect of incorporating cyano or fluoro groups on the mesomorphic and the size of the halide ions of the studied compounds.

Thionitrosyl Complexes of Rhenium and Technetium with PPh3 and Chelating Ligands—Synthesis and Reactivity

In contrast to corresponding nitrosyl compounds, thionitrosyl complexes of rhenium and technetium are rare. Synthetic access to the thionitrosyl core is possible by two main approaches: (i) the treatment of corresponding nitrido complexes with S2Cl2 and (ii) by reaction of halide complexes with trithiazyl chloride. The first synthetic route was applied for the synthesis of novel rhenium and technetium thionitrosyls with the metals in their oxidation states “+1” and “+2”. [MVNCl2(PPh3)2], [MVNCl(PPh3)(LOMe)] and [MVINCl2(LOMe)] (M = Re, Tc; {LOMe}− = (η5-cyclopentadienyl)tris(dimethyl phosphito-P)cobaltate(III)) complexes have been used as starting materials for the synthesis of [ReII(NS)Cl3(PPh3)2] (1), [ReII(NS)Cl3(PPh3)(OPPh3)] (2), [ReII(NS)Cl(PPh3)(LOMe)]+ (4a), [ReII(NS)Cl2(LOMe)] (5a), [TcII(NS)Cl(PPh3)(LOMe)]+ (4b) and [TcII(NS)Cl2(LOMe)] (5b). The triphenylphosphine complex 1 is partially suitable as a precursor for ongoing ligand exchange reactions and has been used for the synthesis of [ReI(NS)(PPh3)(Et2btu)2] (3a) (HEt2btu = N,N-diethyl-N′-benzoyl thiourea) containing two chelating benzoyl thioureato ligands. The novel compounds have been isolated in crystalline form and studied by X-ray diffraction and spectroscopic methods including IR, NMR and EPR spectroscopy and (where possible) mass spectrometry. A comparison of structurally related rhenium and technetium complexes allows for conclusions about similarities and differences in stability, reaction kinetics and redox behavior between these 4d and 5d transition metals.

Synthesis, and molecular docking of thiourea derivatives as antibacterial agents targeting enzymes involved in biosynthesis of bacterial cell wall

Background: New antibacterials are needed due to the increasing resistance of bacteria to existing antibiotics. Thiourea derivative compounds (benzoylthiourea and 1,3-dibenzoylthiourea) contain aromatic groups, thio groups (C=S), and amide groups (H2N-C=O), which are commonly found in the class of antibacterial drugs. Molecular docking can be used to predict their antibacterial activity. Objective: This study aimed to synthesise thiourea derivatives and predict their antibacterial activity by in silico method. Methods: Synthesis was performed using nucleophilic substitution reactions. The synthesised compounds were identified using UV-Vis, FT-IR, and 1H-NMR. Molecular docking was conducted using the MOE program ver 2022.02. Results: Benzoylthiourea (BTU) and 1,3-dibenzoylthiourea (DBTU) compounds were obtained with yields of 36.55% and 12.68%, respectively. The melting point 171-173°C for BTU and 202-204°C for DBTU. Molecular docking results showed higher binding affinity of DBTU against PBP2a (docking score < -5.75 kcal/mol) and FaBH (docking score <-4.7935 kcal/mol) compared to the corresponding native ligands, while the two compounds had lower affinity for the muramyl ligase. Conclusion: BTU and DBTU can be synthesised by nucleophilic substitution reactions. DBTU is predicted to exhibit antibacterial activity against Methicilin Resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis.

Synthesis and characterization of some novel benzoyl thioureas as potent α-glucosidase inhibitors: In vitro and in silico

A series of sixteen benzoyl thiourea derivatives was prepared in good to excellent yield (49–92 %). Eight out of sixteen were reported compounds. The structures of prepared derivatives were elucidated by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic (1H NMR) and carbon nuclear magnetic resonance (13C NMR), and mass spectroscopy (ESI-MS). The structure of two compounds TU-8 and TU-15 was further established by single crystal X-ray diffraction (SCXRD) studies. All of the prepared compounds were screened for their potential as α-glucosidase inhibitor and found to be more potent than standard acarbose. TU-8 and TU-14 were lead compounds with IC50 values 1.59 ± 0.04 µM and 0.60 ± 0.02 µM, respectively. All the prepared compounds were found to non-toxic to fibroblast 3T3-L1 cell lines. The structure activity relation was confirmed by various substituents on phenyl ring. Furthermore, the interaction of compounds with enzyme was confirmed by docking studies. This study proves that synthesized 1, 3-disubstituted thiourea derivatives are excellent α-glucosidase inhibitor and can be exploited to design novel therapeutics to cure type-II diabetes.

Synthesis and Characterization of Silver Nanoparticles Using Amberlite LA-2 Functionalized with Benzoyl Thiourea as a Capping Agent

Synthesis and Characterization of Silver Nanoparticles Using Amberlite LA-2 Functionalized with Benzoyl Thiourea as a Capping Agent

Intelligent nanoreactor coupling tumor microenvironment manipulation and H2O2-dependent photothermal-chemodynamic therapy for accurate treatment of primary and metastatic tumors

Tumor microenvironment (TME), as the “soil” of tumor growth and metastasis, exhibits significant differences from normal physiological conditions. However, how to manipulate the distinctions to achieve the accurate therapy of primary and metastatic tumors is still a challenge. Herein, an innovative nanoreactor (AH@MBTF) is developed to utilize the apparent differences (copper concentration and H2O2 level) between tumor cells and normal cells to eliminate primary tumor based on H2O2-dependent photothermal-chemodynamic therapy and suppress metastatic tumor through copper complexation. This nanoreactor is constructed using functionalized MSN incorporating benzoyl thiourea (BTU), triphenylphosphine (TPP), and folic acid (FA), while being co-loaded with horseradish peroxidase (HRP) and its substrate ABTS. During therapy, the BTU moieties on AH@MBTF could capture excessive copper (highly correlated with tumor metastasis), presenting exceptional anti-metastasis activity. Simultaneously, the complexation between BTU and copper triggers the formation of cuprous ions, which further react with H2O2 to generate cytotoxic hydroxyl radical (•OH), inhibiting tumor growth via chemodynamic therapy. Additionally, the stepwise targeting of FA and TPP guides AH@MBTF to accurately accumulate in tumor mitochondria, containing abnormally high levels of H2O2. As a catalyst, HRP mediates the oxidation reaction between ABTS and H2O2 to yield activated ABTS•+. Upon 808 nm laser irradiation, the activated ABTS•+ performs tumor-specific photothermal therapy, achieving the ablation of primary tumor by raising the tissue temperature. Collectively, this intelligent nanoreactor possesses profound potential in inhibiting tumor progression and metastasis.

Liquid Crystalline and Gel Properties of Luminescent Cyclometalated Palladium Complexes with Benzoylthiourea Ligands.

The design and development of new luminescent metallogels formed by cyclometalated palladium(II) complexes in protic solvents were investigated by a combination of differential scanning calorimetry (DSC), polarized optical microscopy (POM), and rheology. Cyclometalated palladium(II) complexes based on imine ligand and ancillary benzoylthiourea (BTU) ligand showed red emission in solid and gel states. The formation of a lyotropic liquid crystal phase was observed for the complex bearing shorter alkyl groups on the BTU ligand. This complex also behaved as a thermotropic liquid crystal that displays a monotropic smectic A phase (SmA). Dynamic rheology measurements (frequency sweep in the 5-90 °C range) of the 1-decanol solution of palladium(II) complexes highlighted their supramolecular self-association ability to generate 3D networks and form gels as a final result.

Intelligent gold nanoparticles for malignant tumor treatment via spontaneous copper manipulation and on-demand photothermal therapy based on copper induced click chemistry.

The excessive copper in tumor cells is crucial for the growth and metastasis of malignant tumor. Herein, we fabricated a nanohybrid to capture, convert and utilize the overexpressed copper in tumor cells, which was expected to achieve copper dependent photothermal damage of primary tumor and copper-deficiency induced metastasis inhibition, generating accurate and effective tumor treatment. The nanohybrid consistsed of 3-azidopropylamine, 4-ethynylaniline and N-aminoethyl-N'-benzoylthiourea (BTU) co-modified gold nanoparticles (AuNPs). During therapy, the BTU segment would specifically chelate with copper in tumor cells after endocytosis to reduce the intracellular copper content, causing copper-deficiency to inhibit the vascularization and tumor migration. Meanwhile, the copper was also rapidly converted to be cuprous by BTU, which further catalyzed the click reaction between azido and alkynyl on the surface of AuNPs, resulting in on-demand aggregation of these AuNPs. This process not only in situ generated the photothermal agent in tumor cells to achieve accurate therapy avoiding unexpected damage, but also enhanced its retention time for sustained photothermal therapy. Both in vitro and in vivo results exhibited the strong tumor inhibition and high survival rate of tumor-bearing mice after application of our nanohybrid, indicating that this synergistic therapy could offer a promising approach for malignant tumor treatment. STATEMENT OF SIGNIFICANCE: The distinctive excessive copper in tumor cells is crucial for the growth and metastasis of tumor. Therefore, we fabricated intelligent gold nanoparticles to simultaneously response and reverse this tumorigenic physiological microenvironment for the synergistic therapy of malignant tumor. In this study, for the first time we converted and utilized the overexpressed Cu2+ in tumor cells to trigger intracellular click chemistry for tumor-specific photothermal therapy, resulting in accurate damage of primary tumor. Moreover, we effectively manipulated the content of Cu2+ in tumor cells to suppress the migration and vascularization of malignant tumor, resulting in effective metastasis inhibition.

Integration of Tumor Elimination And Tissue Regeneration via Selective Manipulation of Physiological Microenvironments Based on Intelligent Nanocomposite Hydrogel for Postoperative Treatment of Malignant Melanoma

AbstractTumor residue and tissue damage normally occurred after surgical treatment of malignant melanoma, and the effective postoperative therapy is still a challenge because the treatment requests simultaneous but opposite manipulation of tumor cells and healthy cells. Herein, MBGP‐Gel, a thermosensitive and biodegradable hydrogel incorporating S‐nitrosoglutathione (GSNO) loaded and N‐aminoethyl‐N’‐benzoyl thiourea (BTU) modified MSNs (MBGP NPs), was designed to utilize the significant difference of copper content between tumor cells and healthy cells to regulate various physiological microenvironments for integrative therapy of tumor elimination, metastasis inhibition and tissue regeneration. The MBGP‐Gel underwent sol‐gel transformation at body temperature after injection, and continuously released MBGP nanoparticles. In tumor cells, these nanoparticles would chelate the excess copper to inhibit the tumor migration. Meanwhile, copper was reduced to cuprous, which further catalyzed the abundant H2O2 and GSNO to produce oxygen species (ROS) and nitric oxide (NO), respectively. The ROS and the reaction product of ROS and NO (ONOO) would significantly damage the tumor tissue. In contrast, MBGP nanoparticles entered healthy cells only generate appropriate amount of NO to accelerate tissue healing. Both in vitro and in vivo results showed that the nanocomposite hydrogel could inhibit the growth and metastasis of malignant melanoma and promote the skin regeneration, which offered an promising strategy for postoperative treatment of various tumors.

Revealing the contributions of DFT to the spectral interpretation for an amino benzoyl thiourea derivative: Insights into experimental studies from theoretical perspectives, and biological evaluation

2-Amino-N-(phenylcarbamothioyl)benzamide (APCB), an amino benzoyl thiourea derivative, was synthesized via ring opening nucleophilic substitution reaction.

Free radical scavenging, antibacterial potentials and spectroscopic characterizations of benzoyl thiourea derivatives and their metal complexes

In this work, two series of benzoyl thiourea derivatives (TH01-TH05), (TH06-TH10) and their metal complexes were successfully synthesized in good yields (up to 90%) using efficient two-pot synthesis by reacting isothiocyanate with amines and amino acids. The FTIR, 1HNMR, 13CNMR and MALDI-TOF-MS were used for structural elucidation. The FTIR spectra of first series (TH01-TH05) displayed broad absorption band of -OH group at 3600-2800 cm−1 while for 2nd series (TH06-TH10) the absence of OH confirmed the synthesis. The 1HNMR spectra confirmed the synthesis of 1st series have shown singlet peak at 10 to 11.480 ppm for OH proton and two singlets for NH protons at 11.105 ppm and 10.790 ppm respectively. The 13CNMR confirmed synthesis of 1st series by appearance of peaks at 181.328 ppm for (C=S), 170.308 ppm and 168.680 ppm for two (C=O) and aromatic carbons at 133.56-128.954 ppm. The MALDI-TOF-MS results showed presence of molecular ion peaks at appropriate positions. Antimicrobial activity results showed that TH-01, TH-08 and TH-09 have promising antibacterial potential against K. pneumoniae (12 mm) and P. aeruginosa (16 mm and 14 mm) respectively. The DPPH radical scavenging activity of Co-TH05 showed more potential with IC50 value 11.4±0.2 µg/mL than standard ascorbic acid (IC50 10.8±0.5 µg/mL). Results confirmed that the synthesized thiourea derivatives can be efficiently used as radical scavenger and antimicrobial agents.

DFT Studies and Quantum Chemical Calculations of Benzoyl Thiourea Derivatives Linked to Morpholine and Piperidine for the Evaluation of Antifungal Activity

Background: Benzoyl thiourea derivatives linked to morpholine and piperidine have been reported to possess good antifungal activity. Objective: The aim of the study was to find the correlations between the quantum chemical calculations and the antifungal activity of the benzoyl thiourea derivatives linked to morpholine and piperidine. Methods: Optimization of six compounds BTP 1-3 and BTM 4-6 was carried out with DFT using B3LYP method utilizing 6-31G(d,p) basis set. The structural parameters of the compounds as molecular geometry, bond lengths, bond angles, atomic charges and HOMOLUMO energy gap have been investigated and compared with the reported experimental results. Results: A good correlation between the quantum chemical calculations and the antifungal activity of the benzoyl thiourea derivatives linked to morpholine and piperidine was found. Conclusion: The DFT study of benzoyl thiourea derivatives linked to morpholine and piperidine conducted with respect to their Quantum chemical parameters for evaluation of their antifungal activity showed good correlations between the antifungal activity and the quantum chemical parameters.

Corrosion Inhibition characteristics of Reinforced Steel in H2SO4 by benzoyl Thiourea

In The adsorption and corrosion inhibition performance of 3,3-diethyl(4-Chloro)benzoylthiourea, ClDEBT, at reinforced steel in H2SO4 interface was examined using gravimetric method at 303.15 K. The inhibition effectiveness of ClDEBT was improved by increasing the concentration. The adsorption data of ClDEBT on the reinforced steel surface were fitted to Langmuir, Temkin and thermodynamic–kinetic adsorption isotherms, and some thermo-dynamics functions as α, y, f, ΔGads and Kads were obtained. Activation energies of 35.69 and 55.99 kJ mol−1 for the corrosion processes of reinforced steel were observed in presence and absence of benzoylthiourea inhibitor, respectively. The adsorption of thiourea inhibitor on the surface of reinforced steel was found to be spontaneous and exothermic. Quantum parameters as the highest & lowest occupied molecular orbital energy (EHOMO) & (ELUMO), energy gap (ΔE), were determined and correlated to the experimental data.

Electrochemical Studies Of Novel 3,4-Dichloro-N-((5-ChloroPyridin-2-yl)Carbamothioyl)Benzamide Based On Its Complexes With Copper(II), Cobalt(II), Nickel(II) and Zinc(II) ions

The synthesis of novel N,Nʹ-disubstituted benzoyl thiourea ligand [3,4-dichloro-N-((5-chloropyridin-2-yl)carbamothioyl) benzamide] (L) is achieved in two steps. First step by refluxing KSCN with 3,4-dichloro benzoyl chloride in CH3CN solvent and the other step by the reaction of the resulting filtrate from the first step with 2-amino-5-chloropyridine. The copper(II), Cobalt(II), Nickel(II) and Zinc(II) chloride and acetate salts were coordinated with L ligand in the 1:1 and 1:2 mole ratios (M:L) in the solvent mixture of DMF/H2O or CHCl3/methanol to form the complexes with structural formulas {[LMCl2] and [L2M](CH3COO)2, M= Copper(II), Cobalt(II), Nickel(II) and Zinc(II) ions}. Two mole ratios of the starting materials, 1:1 and 1:2 (M:L) were experimented to form chloride complexes, the product was with structural formula [LMCl2] while acetate complexes with [L2M](CH3COO)2 formula are resulted with the same conditions. Ligand L and its complexes [LCuCl2], [LCoCl2], [LNiCl2], [LZnCl2], [L2Cu](CH3COO)2, [L2Co](CH3COO)2, [L2Ni](CH3COO)2 and [(L)2Zn](CH3COO)2 have been characterized by mass spectrometry, elemental analysis, magnetic moments, conductivity measurements, solubility test, UV-visible, FTIR, 1H and 13C NMR spectroscopies. Electrochemical studies were probed by using cyclic voltammetry technique(CV). The data reflect the quasi-reversible reductive nature for the Copper(II) complexes with one electron transfer process while Nickel(II) and Cobalt(II) complexes exhibited two consecutive irreversible reductive nature. The observed UV-visible, elemental analysis, molar conductivity, magnetic moment measurements and solubility test revealed that the metal ion in the all prepared complexes adopted four coordinated square planar structures and [LCuCl2], [LCoCl2], [LNiCl2], [LZnCl2], are formed as neutral complexes while [L2Cu](CH3COO)2, [L2Co](CH3COO)2, [L2Ni](CH3COO)2 and [(L)2Zn](CH3COO)2 adopted anion complexes. The observed magnetic moments show diamagnetic properties of Zinc(II) and Nickel(II) complexes while Copper(II) and Cobalt(II) appeared as paramagnetic species. FT-IR analysis confirmed the coordination sites between the central metal ion with ligand L through two sites, the nitrogen atom in pyridyl ring and the sulphur atom in C=S group

Synthesis, characterization, anti-inflammatory and anti-Helicobacter pylori activities of novel benzophenone tetracarboxylimide benzoyl thiourea cross-linked chitosan hydrogels

Chitosan (Cs) was cross-linked with four various quantities of 4,4′-(5,5′‑carbonylbis(1,3-dioxoisoindoline-5,2-diyl))dibenzoyl isothiocyanate. Elemental analysis, FTIR and 1H NMR spectroscopy assured that the amino groups of chitosan reacted with the isothiocyanate groups of the cross-linker producing four new hydrogels namely as BBTU-Cs-1, BBTU-Cs-2, BBTU-Cs-3, and BBTU-Cs-4 according to the increment of their cross-linking content, respectively. SEM showed their porous structures and XRD indicated their amorphous nature. Their swell ability increased with decreasing the medium pH value and with increasing cross-linking density. In comparison with the popular COX inhibitor Celecoxib, these hydrogels showed an inhibition activity towards COX enzymes with selective inhibition towards COX-2. Their inhibition activity could be arranged as follows: Celecoxib > BBTU-Cs-4 > BBTU-Cs-3 > BBTU-Cs-2 > BBTU-Cs-1. BBTU-CS-4 hydrogel exhibited a potent inhibition against COX-2 (IC50 0.42 μg/ml) compared with that observed for the standard Celecoxib (IC50 0.26 μg/ml). BBTU-Cs-4 is more potent against H. pylori compared to the other hydrogels. BBTU-Cs-4 at a concentration of 7.81 μg/ml is able to kill 100% of the H. pylori and exhibits a preferential ability to inhibit 89.35% of COX-2 than COX-1 (0%). These findings make BBTU-Cs-4 a promising anti-H. pylori and selective anti-inflammatory agent.

ANTIBACTERIAL ACTIVITY OF BENZOYL AND HALOBENZOYL THIOUREA BEARING α- AND β-ALANINE

Antibacterial activity of synthetically synthesized benzoyl thiourea and halobenzoyl thiourea bearing α-alanine and β-alanine compounds were investigated against gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and gram-negative bacteria (Esherichia coli). The study of antibacterial activity of the compounds was conducted by using the disc diffusion method and minimal inhibitory concentration (MIC) as well as minimal bactericidal concentration (MBC). The results indicate that 4-fluorobenzoylthiourea α-alanine, benzoylthiourea α-alanine, 4-fluorobenzoylthiourea β-alanine, 4-chlorobenzoylthiourea β-alanine, 4-bromobenzoylthiourea β-alanine, and benzoylthiourea β-alanine possess weak to strong antibacterial activity on all of tested bacteria. The strongest antibacterial activity was found in the 4-fluorobenzoylthiourea α-alanine, whereas the weakest antibacterial activity was exhibited in 4-fluorobenzoylthiourea β-alanine. S. aureus was found the most susceptible toward these thiourea derivatives, indicating bactericidal activity against the bacteria.

تحضير ودراسة معقدات-N (5,4,3-ثلاثي ميثوكسي فنيل)--N بنزويل ثايويوريا مع عدد من العناصر الانتقالية وأهميتها الصناعية والطبية

This paper performance for preparation and identification of six new complexes of a number of transition metals Cr (lII), Mn (I1), Fe (l), Co (II), Ni (I1), Cu (Il) with: N - (3,4,5-Trimethoxy phenyl-N - benzoyl Thiourea (TMPBT) as a bidentet ligand. The prepared complexes have been characterized, identified on the basis of elemental analysis (C.H.N), atomic absorption, molar conductivity, molar-ratio ,pH effect study, I. Rand UV spectra studies. The complexes have the structural formula ML2X3 for Cr (III), Fe (III), and ML2X2 for Mn (II), Ni (II), and MLX2 for Co (Il) , Cu (Il).

A novel gold(I)-mediated intramolecular transamidation of benzoyl thiourea derivatives to form benzamides via dethiocyanation

A novel gold(I)-mediated intramolecular transamidation of thiourea derivatives to yield benzamides via dethiocyanation have been achieved by the reaction of 3-(1,3-benzothiazol-2-yl)-1-(benzoyl)thiourea derivatives in the presence of gold(I) precursors. The compounds have been characterized using IR, NMR, GC-MS and microanalysis. The single crystal XRD of 3-(1,3-benzothiazol-2-yl)-1-(3-bromobenzoyl)thiourea (5), 3-(1,3-benzothiazol-2-yl)-1-(3-methoxybenzoyl)thiourea (6), N-(benzothiazol-2-yl)benzamide (10), N-(benzothiazol-2-yl)-3-chlorobenzamide (11), N-(benzothiazol-2-yl)-4-nitrobenzamide (12), N-(benzothiazol-2-yl)-3-bromobenzamide (14) have been discussed. The novel transformation is thought to proceed by a gold(I)-mediated intramolecular transamidation reaction which releases thiocyanate to yield the benzamide. Density functional theory calculations have been used to support the proposed mechanism for this transformation.

Microwave Synthesis, Characterization, Biological Activity of N- (p-Chlorophenyl)-N'-Benzoyl Thiourea and its Complexes

A derivative of thiourea ligand N-(p-chlorophenyl)-N'-Benzoyl thiourea (PCBT) in equimolar ratio 1:1 and its transition metal complexes CoII, NiII , CuII and ZnII were synthesized by microwave (green chemistry). The structure of ligand and its complexes have been characterized by using elemental analysis, mass Spectroscopy, FT-IR, UV-Vis., 1HNMR and 13CNMR. The geometry of the proposed structures of the chelates based on their electronic spectra, electron spin resonance (ESR) and magnetic susceptibility. The stability of complexes was studied by TGA analysis (Thermal studies). The free derivative thiourea ligand (PCBT) and its complexes were studied for antimicrobial and antifungal activity.

Design, synthesis and biological evaluation of novel tetrahydrothieno [2,3-c]pyridine substitued benzoyl thiourea derivatives as PAK1 inhibitors in triple negative breast cancer

The overexpression of P21-activated kinase 1 (PAK1) is associated with poor prognosis in several cancers, which has emerged as a promising drug targets. Based on high-throughput virtual screening strategy, tetrahydrothieno [2,3-c]pyridine scaffold was identified as an initial lead for targeting PAK1. Herein we reported our structure-based optimisation strategy to discover a potent PAK1 inhibitor (7j) which displayed potent PAK1 inhibition and antiproliferatory activity in MDA-MB-231 cells. 7j induced obviously G2/M cell cycle arrest via PAK1-cdc25c-cdc2 pathway, and also inhibited MAPK-ERK and MAPK-JNK cascade to induce MDA-MB-231 cell death. Together, these results provided a novel chemical scaffold as PAK1 inhibitor for breast cancer treatment.