Synthesis,structures and urease inhibitory activity of cobalt(III) complexes with Schiff bases

A series of new cobalt(III) complexes were prepared. They are [CoL¹(py)₃]·NO₃ (1), [CoL²(bipy)(N₃)]·CH₃OH (2), [CoL³(HL³)(N₃)]·NO₃ (3), and [CoL⁴(MeOH)(N₃)] (4), where L¹, L², L³ and L⁴ are the deprotonated form of N′-(2-hydroxy-5-methoxybenzylidene)-3-methylbenzohydrazide, N′-(2-hydroxybenzylidene)-3-hydroxylbenzohydrazide, 2-[(2-dimethylaminoethylimino)methyl]-4-methylphenol, and N,N′-bis(5-methylsalicylidene)-o-phenylenediamine, respectively, py is pyridine, and bipy is 2,2′-bipyridine. The complexes were characterized by infrared and UV–Vis spectra, and single crystal X-ray diffraction. The Co atoms in the complexes are in octahedral coordination. Complexes 1 and 4 show effective urease inhibitory activities, with IC₅₀ values of 4.27 and 0.35 μmol L⁻¹, respectively. Complex 2 has medium activity against urease, with IC₅₀ value of 68.7 μmol L⁻¹. While complex 3 has no activity against urease. Molecular docking study of the complexes with Helicobacter pylori urease was performed.     

Bifunctional bisphosphonate derivatives and platinum complexes with high affinity for bone hydroxyapatite

A series of ethylenediamine/1,3-propanediamine derivatives containing bifunctional bisphosphonate substituents and their corresponding dichloroplatinum(II) complexes have been synthesized and characterized by elemental analysis, ¹H NMR, ¹³C NMR, ³¹P NMR, and HRMS spectra. Based on WST-8 assay with CCK-8, in general, the newly synthesized dichloroplatinum complexes 1–6 showed higher in vitro antitumor activity than platinum-free compounds L1–L6 against three tumor cell lines (especially osteosarcoma MG-63). According to hydroxyapatite binding experiment, complexes 2, 3, and 6 showed much higher affinity (K′ = 3.7, 4.0, and 3.0, respectively) for bone hydroxyapatite than cisplatin (K′ < 0.1), comparable to zoledronate (K′ = 2.8). It can be found that representative complex 2 with high cytotoxicity and in vitro antiproliferative activity against osteosarcoma cell line, as well as promising hydroxyapatite binding ability has been screened as a potential bone-targeting antitumor agent for subsequent in vivo study. In addition, flow cytometry experiment was applied to investigate the mode of action of representative complex 2.     

Chemical access to the mononuclear Mn(III) [(mL)Mn(OMe)]+ complex (mLH = N,N′-bis-(2-pyridylmethyl)-N-(2-hydroxybenzyl)-N′-methyl-ethane-1,2-diamine) and electrochemical oxidation to the Mn(IV) [(mL)Mn(OMe)]2+ species

Chemical oxidation in acetonitrile of the previously reported phenolato-bridged binuclear Mn(II) complex [(mL)MnMn(mL)]²⁺ (1), where mLH is pentadentate N,N′-bis-(2-pyridylmethyl)-N-(2-hydroxybenzyl)-N′-methyl-ethane-1,2-diamine ligand [C. Hureau, et al., Chem. Eur. J. 2004, 10, 1998–2010] using iodosylbenzene PhIO (dissolved in methanol) is described. The addition of one to four equivalents of PhIO per Mn ion leads to the transient formation of the mono-μ-oxo binuclear Mn₂(III,III) complex [(mL)Mn(μ-O)Mn(mL)]²⁺ (2), previously studied. After addition of five equivalents of PhIO per Mn ion, the mononuclear Mn(III) species [(mL)Mn(OMe)]⁺ (3) is quantitatively generated. The UV–Vis spectrum of 3 displays a broad band at 456 nm (ε = 1000 L mol⁻¹ cm⁻¹) attributed to phenolato to Mn(III) charge transfer transition. Complex 3 exhibits a reversible oxidation wave at E^1/2 = 0.68 V versus SCE, and the mononuclear Mn(IV) complex [(mL)Mn(OMe)]²⁺ (3^ox) can thus be generated by exhaustive electrolysis at 1.0 V versus SCE. The 9.4 GHz EPR spectrum of complex 3^ox shows a strong transition near g = 4 consistent with a rhombically distorted S = 3/2 system with a zero-field splitting dominating the Zeeman effect. UV–Vis spectrum displays a large phenolato to Mn(IV) charge transfer transition at 670 nm (ε = 2450 L mol⁻¹ cm⁻¹).     

Cyclic ferrocenylnaphthalene diimide derivative as a new class of G-quadruplex DNA binding ligand

To identify an effective ligand that binds to a G-quadruplex structure but not a double-stranded DNA (dsDNA), a set of biophysical and biochemical experiments were carried out using newly synthesized cyclic ferrocenylnaphthalene diimide (cFNDI, 1) or the non-cyclic derivative (2) with various structures of G-quadruplex DNAs and dsDNA. Compound 1 bound strongly to G-quadruplexes DNAs (10⁶ M^?1 order) with diminished binding to dsDNA (10⁴ M^?1 order) in 100 mM AcOH-AcOK buffer (pH 5.5) containing 100 mM KCl. Interestingly, 1 showed an approximately 50-fold higher selectivity to mixed hybrid-type telomeric G-quadruplex DNA (K = 3.4 × 10⁶ M^?1 and a 2:1 stoichiometry) than dsDNA (K = 7.5 × 10⁴ M^?1) did. Furthermore, 1 showed higher thermal stability to G-quadruplex DNAs than it did to dsDNA with a preference for c-kit and c-myc G-quadruplex DNAs over telomeric and thrombin binding aptamers. Additionally, 1 exhibited telomerase inhibitory activity with a half-maximal inhibitory concentration (IC₅₀) of 0.4 μM. Compound 2 showed a preference for G-quadruplex; however, the binding affinity magnitude and preference were improved in 1 because the former had a cyclic structure.     

Novel pyrazole integrated 1,3,4-oxadiazoles: Synthesis,characterization and antimicrobial evaluation

A novel series of 2-(5-methyl-1,3-diphenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazoles 7(a–m) were synthesized either by cyclization of N′-benzoyl-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 4a using POCl₃ at 120 °C or by oxidative cyclization of hydrazones derived from various arylaldehyde and (E)-N′-benzylidene-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 5(a–d) using chloramine-T as oxidant. Newly synthesized compounds were characterized by analytical and spectral (IR, ¹H NMR, ¹³C NMR and LC–MS) methods. The synthesized compounds were evaluated for their antimicrobial activity and were compared with standard drugs. The compounds demonstrated potent to weak antimicrobial activity. Among the synthesized compounds, compound 7m emerged as an effective antimicrobial agent, while compounds 7d, 7f, 7i and 7l showed good to moderate activity. The minimum inhibitory concentration of the compounds was in the range of 20–50 μg mL⁻¹ against bacteria and 25–55 μg mL⁻¹ against fungi. The title compounds represent a novel class of potent antimicrobial agents.     

Radiosynthesis and evaluation of new PET ligands for peripheral cannabinoid receptor type 1 imaging

Cannabinoid receptor type 1 (CB1) is mainly expressed in the brain, as well as being expressed in functional relevant concentrations in various peripheral tissues. 1-(4-Chlorophenyl)-3-(3-(6-(pyrrolidin-1-yl)pyridin-2-yl)phenyl)urea (PSNCBAM-1, 1) was developed as a potent allosteric antagonist for CB1 and its oral administration led to reductions in the appetite and body weight of rats. Several analogs of 1 (compounds 2 and 3) were recently identified through a series of structure-activity relationship studies. Herein, we report the synthesis of radiolabeled analogs of these compounds using [¹¹C]COCl₂ and an evaluation of their potential as PET ligands for CB1 imaging using in vitro and in vivo techniques. [¹¹C]2 and [¹¹C]3 were successfully synthesized in two steps using [¹¹C]COCl₂. The radiochemical yields of [¹¹C]2 and [¹¹C]3 were 17 ± 8% and 20 ± 9% (decay-corrected to the end of bombardment, based on [¹¹C]CO₂). The specific activities of [¹¹C]2 and [¹¹C]3 were 42 ± 36 and 37 ± 13 GBq/μmol, respectively. The results of an in vitro binding assay using brown adipose tissue (BAT) homogenate showed that the binding affinity of 2 for CB1 (K_D = 15.3 µM) was much higher than that of 3 (K_D = 26.0 µM). PET studies with [¹¹C]2 showed a high uptake of radioactivity in BAT, which decreased in animals pretreated with AM281 (a selective antagonist for CB1). In conclusion, [¹¹C]2 may be a useful PET ligand for imaging peripheral CB1 in BAT.     

Synthesis,potential anti-inflammatory and analgesic activities study of (S)-N-substituted-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamides

A series of (S)-N-substitued-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamide derivatives were designed, synthesized and evaluated for their anti-inflammatory and analgesic effects in vivo. Among the synthesized compounds 2a and 2n showed the best anti-inflammatory activity (inhibition rate: 95% and 92.7%, respectively) and analgesic effect (inhibition rate: 100% and 100%, respectively), which was greater than that or nearly equivalent to that of indomethacin. Compounds 2a and 2n were selected to test their inhibitory effects against ovine COX-1 and COX-2 using the cyclooxygenase inhibition assay in vitro. Compounds 2a and 2n are weak inhibitors of COX-1 isozyme but displayed moderate COX-2 isozyme inhibitory effects (IC₅₀ = 0.47 μM and 1.63 μM, respectively) and COX-2 selectivity indexes (SI = 11.5 and 4.8). Furthermore, compound 2a was more inhibitors of COX-2 isozyme active than the reference drug celecoxib.     

Synthesis and structure–activity relationships of N-benzyl-N-(X-2-hydroxybenzyl)-N′-phenylureas and thioureas as antitumor agents

Two series of novel N-benzyl-N-(X-2-hydroxybenzyl)-N′-phenylureas and thioureas (1a–18a; 1b–18b) as potential EGFR and HER-2 kinase inhibitors have been discovered. These compounds displayed good EGFR and HER-2 inhibitory activity and the SARs are also been studied. Especially compound 7b demonstrated significant EGFR and HER-2 inhibitory activity (IC₅₀ = 0.08 μM for EGFR and IC₅₀ = 0.35 μM for HER-2). Docking simulation was performed to position compound 7b into the EGFR active site to determine the probable binding conformation and antiproliferative assay results indicating that these series of urea and thioureas own high antiproliferative activity against MCF-7. Above all, thiourea 7b would be a potential anticancer agent deserves further research.     

Synthesis,structures and characterization of the dinuclear nickel(II) complexes containing N,N,N′,N′-tetrakis[(1-ethyl-2-benzimidazolyl)methyl]-2-hydroxy-1,3-diaminopropane and an azide ion

Two dinuclear nickel(II) complexes, [Ni₂(L-Et)(N₃)(H₂O)₃](NO₃)₂ · 2H₂O (1) and [Ni₂(L-Et)(μ-1,3-N₃)(H₂O)₂](NO₃)₂ · 4H₂O (2) containing (HL-Et = N,N,N′,N′-tetrakis[(1-ethyl-2-benzimidazolyl)methyl]-2-hydroxy-1,3-diaminopropane), have been synthesized and characterized by their IR and UV–Vis spectra and magnetic susceptibilities. The crystal structures of [Ni₂(L-Et)(N₃)(H₂O)₃](NO₃)₂ · CH₃OH (1′) and [Ni₂(L-Et)(μ-1,3-N₃)(H₂O)₂](NO₃)₂ · 2C₂H₅OH (2′) similar to 1 and 2 were determined by X-ray crystallography. In 1′, the two nickel(II) ions are bridged by only an alkoxo group of L-Et⁻, while an azido and an alkoxo connect two nickel(II) ions in 2′. Magnetic susceptibility measurements (2–300 K) showed a weak ferromagnetic exchange coupling between the two nickel(II) ions (2J = 10.1 cm⁻¹) for 1. On the other hand, antiferromagnetic interactions were observed for 2 (2J = −15.8 cm⁻¹).     

Identification and development of 2-methylimidazo[1,2-a]pyridine-3-carboxamides as Mycobacterium tuberculosis pantothenate synthetase inhibitors

In the present study, we used crystal structure of mycobacterial pantothenate synthetase (PS) bound with 2-(2-(benzofuran-2-ylsulfonylcarbamoyl)-5-methoxy-1H-indol-1-yl) acetic acid inhibitor for virtual screening of antitubercular compound database to identify new scaffolds. One of the identified lead was modified synthetically to obtain thirty novel analogues. These synthesized compounds were evaluated for Mycobacterium tuberculosis (MTB) PS inhibition study, in vitro antimycobacterial activities and cytotoxicity against RAW 264.7 cell line. Among the compounds tested, N′-(1-naphthoyl)-2-methylimidazo[1,2-a]pyridine-3-carbohydrazide (5b) was found to be the most active compound with IC₅₀ of 1.90 ± 0.12 μM against MTB PS, MIC of 4.53 μM against MTB with no cytotoxicity at 50 μM. The binding affinity of the most potent inhibitor 5b was further confirmed biophysically through differential scanning fluorimetry.     

Improved binding affinities of pyrrolidine derivatives as Mcl-1 inhibitors by modifying amino acid side chains

As an important member of anti-apoptotic Bcl-2 protein, myeloid cell leukemia sequence 1 (Mcl-1) protein is an attractive target for cancer therapy. In this study, a new series of pyrrolidine derivatives as Mcl-1 inhibitors were developed by mainly modifying the amino acid side chain of compound 1. Among them, compound 18 (K_i = 0.077 μM) exhibited better potent inhibitory activities towards Mcl-1 protein compared to positive control Gossypol (K_i = 0.18 μM). In addition, compound 40 possessed good antiproliferative activities against PC-3 cells (K_i = 8.45 μM), which was the same as positive control Gossypol (K_i = 7.54 μM).     

Phytochemical and cytotoxic studies on the leaves of Calotropis gigantea

A new lignan, 9′-methoxypinoresinol (1), and two new glycosylated 5-hydroxymethylfurfurals, calofurfuralside A (2), and calofurfuralside B (3), together with nine known compounds (4–12) have been isolated from the active fractions, CHCl₃ (IC₅₀, 0.32 μg mL^?1) and EtOAc (IC₅₀, 0.55 μg mL^?1) fractions of the leaves of Calotropis gigantea. Their structures were elucidated based on NMR and MS data. Among the isolated compounds, compounds 1 and 9 exhibited potent cytotoxicity against PANC-1 human pancreatic cancer cell line under the normoglycemic condition with IC₅₀ values of 3.7 and 3.3 μM, respectively. 9′-Methoxypinoresinol (1) significantly inhibited the colony formation of PANC-1 cells in a concentration-dependent manner.     

Synthesis and evaluation of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid derivatives as xanthine oxidase inhibitors

This study mainly focused on the modification of the X² position in febuxostat analogs. A series of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid derivatives (1a-s) with an N atom occupying the X² position was designed and synthesized. Evaluation of their inhibitory potency in vitro on xanthine oxidase indicated that these compounds exhibited micromolar level potencies, with IC₅₀ values ranging from 0.21 µM to 26.13 μM. Among them, compound 1s (IC₅₀ = 0.21 μM) showed the most promising inhibitory effects and was 36-fold more potent than allopurinol, but was still 13-fold less potent than the lead compound Y-700, which meant that a polar atom fused at the X² position could be unfavorable for potency. The Lineweaver-Burk plot revealed that compound 1s acted as a mixed-type xanthine oxidase inhibitor. Analysis of the structure-activity relationships demonstrated that a more lipophilic ether tail (e.g., meta-methoxybenzoxy) at the 4′-position could benefit the inhibitory potency. Molecular modeling provided a reasonable explanation for the structure–activity relationships observed in this study.     

Magnetostructural correlations and catecholase-like activities of μ-alkoxo-μ-carboxylato double bridged dinuclear and tetranuclear copper(II) complexes

Two μ-alkoxo-μ-carboxylato bridged dinuclear copper(II) complexes, [Cu₂(L¹)(μ-HCO₂)] (1) ((H₃L¹ = 1,3-bis(5-bromosalicylideneamino)-2-propanol)), [Cu₂(L²)(μ-HCO₂)] · dmf (2) (H₃L² = 1,3-bis(3,5-chlorosalicylideneamino-2-propanol)), and two μ-alkoxo-μ-dicarboxylato doubly bridged tetranuclear copper(II) complexes, [{Cu₂(L³)}₂(μ-O₂C–C(CH₃)₂–CO₂)] · 5H₂O · 3CH₃OH (3) ((H₃L³ = 1,3-bis(salicylid-deneamino)-2-propanol)) and [{Cu₂(L³)}₂(μ- O₂CCH₂–C₆H₄–CH₂CO₂)] · 2H₂O (4) have been prepared and characterized. The single crystal X-ray analysis shows that the structures of complexes 1 and 2 are dimeric with two adjacent copper(II) atoms bridged by μ-alkoxo-μ-carboxylato ligands with the Cu⋯Cu distances and Cu–O(alkoxo)–Cu angles are 3.511 Å and 132.85° for 1, 3.517 Å and 131.7° for 2, respectively. Complexes 3 and 4 consist of μ-alkoxo-μ-dicarboxylato doubly bridged tetranuclear Cu(II) complexes with mean Cu–Cu distances and Cu–O–Cu angles of 3.158 Å and 108.05° for 3 and 3.081 Å and 104.76° for 4, respectively. Magnetic measurements reveal that 1 and 2 are strong antiferromagnetically coupled with 2J = −156 and −152 cm⁻¹, respectively, while 3 and 4 exhibit ferromagnetic coupling with 2J = 86 and 155.2 cm⁻¹, respectively. The 2J values of 1–4 are linearly correlated to the Cu–O–Cu angles. Dependence of the pH at 25 °C on the reaction rate of oxidation of 3,4-di-tert-butylcatechol (3,5-dtbc) to the corresponding quinone catalyzed by 1–4 was studied. Complexes 1–4 exhibit high catecholase-like activity at pH 9.0 and 25 °C for oxidation of 3,5-di-tert-butylcatechol.     

Synthesis and hyperpolarisation of eNOS substrates for quantification of NO production by 1H NMR spectroscopy

Hyperpolarization enhances the intensity of the NMR signals of a molecule, whose in vivo metabolic fate can be monitored by MRI with higher sensitivity. SABRE is a hyperpolarization technique that could potentially be used to image nitric oxide (NO) production in vivo. This would be very important, because NO dysregulation is involved in several pathologies, including cardiovascular ones. The nitric oxide synthase (NOS) pathway leads to NO production via conversion of l-arginine into l-citrulline. NO is a free radical gas with a short half-life in vivo (≈5 s), therefore direct NO quantification is challenging. An indirect method – based on quantifying conversion of an l-Arg- to l-Cit-derivative by ¹H NMR spectroscopy – is herein proposed. A small library of pyridyl containing l-Arg derivatives was designed and synthesised. In vitro tests showed that compounds 4a–j and 11a–c were better or equivalent substrates for the eNOS enzyme (NO₂^? production = 19–46 μM) than native l-Arg (NO₂^? production = 25 μM). Enzymatic conversion of l-Arg to l-Cit derivatives could be monitored by ¹H NMR. The maximum hyperpolarization achieved by SABRE reached 870-fold NMR signal enhancement, which opens up exciting future perspectives of using these molecules as hyperpolarized MRI tracers in vivo.     

Cytochrome P450 binding studies of novel tacrine derivatives: Predicting the risk of hepatotoxicity

The 1,2,3,4-tetrahydroacridine derivative tacrine was the first drug approved to treat Alzheimer’s disease (AD). It is known to act as a potent cholinesterase inhibitor. However, tacrine was removed from the market due to its hepatotoxicity concerns as it undergoes metabolism to toxic quinonemethide species through the cytochrome P450 enzyme CYP1A2. Despite these challenges, tacrine serves as a useful template in the development of novel multi-targeting anti-AD agents. In this regard, we sought to evaluate the risk of hepatotoxicity in a series of C9 substituted tacrine derivatives that exhibit cholinesterase inhibition properties. The hepatotoxic potential of tacrine derivatives was evaluated using recombinant cytochrome (CYP) P450 CYP1A2 and CYP3A4 enzymes. Molecular docking studies were conducted to predict their binding modes and potential risk of forming hepatotoxic metabolites. Tacrine derivatives compound 1 (N-(3,4-dimethoxybenzyl)-1,2,3,4-tetrahydroacridin-9-amine) and 2 (6-chloro-N-(3,4-dimethoxybenzyl)-1,2,3,4-tetrahydroacridin-9-amine) which possess a C9 3,4-dimethoxybenzylamino substituent exhibited weak binding to CYP1A2 enzyme (1, IC₅₀ = 33.0 µM; 2, IC₅₀ = 8.5 µM) compared to tacrine (CYP1A2 IC₅₀ = 1.5 µM). Modeling studies show that the presence of a bulky 3,4-dimethoxybenzylamino C9 substituent prevents the orientation of the 1,2,3,4-tetrahydroacridine ring close to the heme-iron center of CYP1A2 thereby reducing the risk of forming hepatotoxic species.     

Synthesis,characterization and in vitro anti-neoplastic activity of gypsogenin derivatives

Gypsogenin (L¹; 3-hydroxy-23-oxoolean-12-en-28-oic acid), a natural saponin, was isolated from the boiling water extract of Gypsophila arrostii roots. In addition, the derivatives gypsogenin thiosemicarbazone (L²; 23-[(aminocarbonothioyl)hydrazono]-3-hydroxolean-12-en-28-oic acid) and gypsogenin thiosemicarbazone glyoxime (L³H₂; (3β)-3-hydroxy-23-[({[(1Z,2E)-N-hydroxy-2-(hydroxyimino)ethanimidoyl]amino}carbonothioyl)hydrazono] olean-12-en-28-oic acid) as well as the Cu(II) and Co(II) complexes of L³H₂ were prepared. The structures were established on NMR analysis (¹H, ¹³C NMR, HMBC, HMQC, and NOESY), FT-IR and completed by analysis of LC/MS. Furthermore, the antiproliferative effects of the Co(II) and Cu(II) complexes of the gypsogenin derivatives were assayed in human promyelocytic leukemia (HL 60) cells. These complexes were found to be potent anticancer agents with concentrations that inhibited 50% of proliferation (I_pC₅₀) between 5 μM and 40 μM. Cell death was distinguished by HO/PI double staining. The Co(II) complex of L³H₂ has shown approximately %50 apoptotic effect at 10 μM concentration. Paclitaxel has been used as positive control.     

Anti-diabetic xanthones from the bark of Garcinia xanthochymus

An ethyl acetate extract the bark of Garcinia xanthochymus exhibited strong inhibition towards α-glucosidase and PTP1B with IC₅₀ values of 0.3 ± 0.1 μg/mL and 2.3 ± 0.4 μg/mL, respectively. Chemical constituents of the extract were therefore examined, and two new compounds, xanthochymusxanthones A (1) and B (2), along with ten known xanthones (3–12), were isolated. Their structures were determined using spectroscopic methods, mainly 1D and 2D NMR. Inhibitory activity of the isolated compounds was then tested, and subelliptenone F (12) showed significant effect towards α-glucosidase with IC₅₀ value of 4.1 ± 0.3 μM (compared with acarbose, IC₅₀ = 900.0 ± 3.0 μM) whilst xanthochymusxanthone B (2) exhibited remarkable activity towards PTP1B with IC₅₀ value of 8.0 ± 0.6 μM (compared with RK682, IC₅₀ = 4.4 ± 0.3 μM).     

Synthesis of new morpholine-connected pyrazolidine derivatives and their antimicrobial,antioxidant, and cytotoxic activities

A simple and convenient one-pot four-component synthesis of morpholine-connected pyrazolidine derivatives 2a–f and 4a–f was developed using direct metal-free catalysis, with the identities of the synthesized compounds confirmed by IR, NMR (¹H and ¹³C), mass spectrometry, and elemental analysis. The prepared compounds were inspected for antimicrobial, antioxidant, and cytotoxic activities.Antimicrobial and antifungal activities against five bacterial and four fungal pathogens, respectively, were investigated using the disc diffusion technique. In antibacterial activity, compounds 2d and 2f (MIC = 2 μg/mL) exhibited significantly higher activity than the standard ciprofloxacin. The results of antifungal assay showed that the activity of compound 4a (MIC = 0.5 μg/mL) was significantly higher than the standard clotrimazole. Antioxidant activity was screened based on ABTS⁺ radical scavenging and linoleic acid peroxidation performance. Compound 4a showed substantial antioxidant (91.3%) activities, as compared with the Trolox standard. Cytotoxicity was evaluated using HepG2 (liver), HeLa (cervical), and MCF-7 (breast) cancer cell lines, with high toxicities observed for 2b (GI₅₀ = 12.2 μm) and 4a (GI₅₀ = 07.8 μm).     

Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one derivatives containing thiourea and acylthiourea against Meloidogyne incognita

Two series of novel 1,2,3-benzotriazin-4-one derivatives containing thiourea and acylthiourea were designed and synthesized. The bioassay results showed that most of the test compounds showed good nematicidal activity against M. incognita at the concentration of 10.0 mg L^?1in vivo. The compounds A13, A17 and B3 showed excellent nematicidal activity on the second stage juveniles of the root-knot nematode with the inhibition rate of 51.3%, 58.3% and 51.3% at the concentration of 1.0 mg L^?1 respectively. It suggested that the structure of 1,2,3-benzotriazin-4-one derivatives containing thiourea and acylthiourea could be optimized further.