Synthesis,insecticidal, and fungicidal screening of some new quinoline derivatives

This paper describes the synthesis of a series of quinolines graphted with hydrazones, pyrazoles, pyridazine, phthalazine, triazepinone, semicarbazide, and thiomorpholide moieties and four metal complexes. These derivatives were screened against Fusarium oxysporum and the red palm weevil (RPW) Rhynchophorus ferrugineus Oliver (coleopteran: Curculionidae) as palm pathogens. Only chlorinated quinolines were active against these organisms with hydrazones being good fungicides, while those modified with pyrazoles and pyrazines showed moderate insecticidal activity. A unique trihydroxylated hydrazone was active against both organisms, while another hydrazone, the most potent fungicide in this series, exhibited insecticidal activity only upon complexation with Zn²⁺ ions.     

Synthesis,crystal structure,optical properties and antibacterial evaluation of novel imidazo[1, 5‐a]pyridine derivatives bearing a hydrazone moiety

A series of novel imidazo[1,5‐a]pyridine‐hydrazone derivatives were synthesized and characterized by infrared spectroscopy (IR), ¹H NMR, ¹³C NMR and high resolution mass spectrometer (HRMS). Typically, the spatial structure of compound 3j was determined using X‐ray diffraction analysis. The UV–vis absorption and fluorescence spectral characteristics of the compounds in dichloromethane and acetonitrile were investigated. Absorption peaks could be observed in the wavelength range 290–450 nm. It can also be seen that they display very similar maximum emission. The group attached to hydrazone hardly influenced the maximum emission. Furthermore, all the compounds were evaluated for antibacterial activity and were found to be more effective against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa and Shigella compared with chloramphenicol. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis and DNA Binding Studies of Novel Heterocyclic Substituted Quinoline Schiff Bases: A Potent Antimicrobial Agent

The present article deals with the synthesis of 2-chloroquinoline-3-carbaldehyde [(2-hydroxy-1-naphthyl) methylene] hydrazone (CQCMH) (2a-c) and 2-chloroquinoline-3-carbaldehyde [4-(dimethylamino) benzylidene] hydrazone (CQCDBH) (3a-c) from quinoline derivatives under suitable experimental conditions. The synthesized compounds were characterized by elemental analysis, FTIR, ¹HNMR, and mass spectral data. The selected compounds were studied for interaction with calf thymus-DNA (CT-DNA) by electronic spectra, viscosity measurements as well as thermal denaturation studies. On binding to DNA, the absorption spectrum underwent bathochromic and hypochromic shifts. The binding constant (K_b) had value of 2.3×10³ M^?1 for (2a) and 2.5×10⁴ M^?1 for (3a). The viscosity measurements indicated that the viscosity of sonicated rod like DNA fragments increased. The synthesized derivatives have been screened for antibacterial and antifungal activities.     

Synthesis of some novel hydrazone and 2-pyrazoline derivatives: Monoamine oxidase inhibitory activities and docking studies

A novel series of 2-pyrazoline and hydrazone derivatives were synthesized and investigated for their human monoamine oxidase (hMAO) inhibitory activity. All compounds inhibited the hMAO isoforms (MAO-A or MAO-B) competitively and reversibly. With the exception of 5i, which was a selective MAO-B inhibitor, all derivatives inhibited hMAO-A potently and selectively. According to the experimental K_i values, compounds 6e and 6h exhibited the highest inhibitory activity towards the hMAO-A, whereas compound 5j, which carries a bromine atom at R⁴ of the A ring of the pyrazoline, appeared to be the most selective MAO-A inhibitor. Tested compounds were docked computationally into the active site of the hMAO-A and hMAO-B isozymes. The computationally obtained results were in good agreement with the corresponding experimental values.     

Synthesis and antiviral,insecticidal, and fungicidal activities of gossypol derivatives containing alkylimine,oxime or hydrazine moiety

Gossypol is a part of the cotton plant’s defense system against pathogens and herbivorous insects. To discover gossypol analogs with broad spectrum and high activity, a series of gossypol alkylamine Schiff base, oxime and hydrazone derivatives were synthesised and bioassayed. The biological results indicated that most of these derivatives exhibited higher anti-TMV activity than gossypol. Interestingly, the activities of compounds 10, 15, 18, 20, 23 and 26 were much higher than that of ribavirin. Furthermore, compound 26, which was low toxicity to rat, showed better activity than control plant virus inhibitors in the field. Additionally, allyl amine Schiff base (9) displayed remarkable insecticidal activities against Mythimna separata, Helicoverpa armigera and Ostrinia nubilalis, whereas (pyridin-3-yl)methanamine Schiff base (13) showed excellent activity against Culex pipiens pallens. The fungicidal results revealed that all of compounds exhibited good activity against Physalospora piricola.     

Melatonin analogue new indole hydrazide/hydrazone derivatives with antioxidant behavior: Synthesis and structure–activity relationships

Melatonin (MLT) is a hormone produced in the brain by the pineal gland, from the amino acid tryptophan. It is also an antioxidant hormone with a particular role in the protection of nuclear and mitochondrial DNA. In recent years, many physiological properties of MLT have been described resulting in much attention in the development of synthetic compounds possessing the indole ring. Sixteen MLT analogue indole hydrazide/hydrazone derivatives were synthesized and in vitro antioxidant activity was investigated. Most of the compounds showed significantly higher activity than MLT at 10^{? 3} M and 10^{? 4} M concentrations.     

New Hydrazides and Hydrazide‐Hydrazones of 2,3‐Dihalogen Substituted Propionic Acids: Synthesis and in vitro Antimicrobial Activity Evaluation

The main aim of this research was the synthesis, spectral identification and in vitro antimicrobial evaluation of new hydrazides and hydrazide‐hydrazones of 2,3‐dihalogen substituted propionic acids. New hydrazides were obtained by the substitution reaction of appropriate ethyl esters of 2,3‐dihalogen substituted propionic acids with hydrazine hydrate. Then obtained hydrazides were subjected to condensation reaction with various aldehydes which yielded with new hydrazide‐hydrazone derivatives. All obtained compounds were identified on the basis of spectral methods (¹H‐NMR, ¹³C‐NMR) and in vitro screened against a panel of bacterial and fungal strains according to EUCAST and CLSI guidelines.     

Design,synthesis, and pharmacological evaluation of 2-(4-sulfonylphenyl)-2-[(E)-pyrrolidin-1-ylimino]-N-thiazoleacetamides as glucokinase activators

This paper presents the synthesis and glucokinase activity of novel hydrazone derivatives. The 2-(4-cyclopropylsulfonylphenyl)-2-[(E)-pyrrolidin-1-ylimino]-acetamide derivatives 5a–5h presented the in vitro glucokinase activities and in vivo blood glucose-lowering effects in mice. Particularly, 5h showed an oral hypoglycemic effect in rats at 1 mg/kg. These hydrazone derivatives are a potential new class of glucokinase activators for the treatment of type 2 diabetes.     

Antiviral properties and interaction of novel chalcone derivatives containing a purine and benzenesulfonamide moiety

A new concise and facile method was explored to synthesize a series of novel chalcone derivatives containing a purine and benzenesulfonamide moiety and their antiviral properties were evaluated against TMV and CMV. Biological assays indicated that several of the derivatives exhibited significant anti-TMV and anti-CMV activities in vivo. In particular, compound d2 displayed excellent inactivating activity against TMV, with the EC₅₀ value of 51.65?μg/mL, which was better than that of ribavirin (150.45?μg/mL). Molecular docking showed that there are four hydrogen bonds between compound d2 and TMV coat protein (TMV-CP). Compound d2 demonstrated strong binding capacity to TMV-CP with K_a?=?1.58?×?10⁵?L/mol and K_d?=?12.16?μM. These findings indicated that chalcone derivatives are worthy of further research and development as templates for new antiviral agents.     

Synthesis and anticandidal evaluation of new benzothiazole derivatives with hydrazone moiety

In this study, we have performed the synthesis of new N′-(arylidene)-4-[(benzothiazol-2-yl)thio]butanoylhydrazide derivatives (3a–s) bearing azole moiety and hydrazone group in a lipophilic structural framework. The target compounds were prepared by a three step synthetic procedure starting from 2-mercaptobenzothiazole. The structures of the target compounds were elucidated by IR, ¹H NMR, ¹³C NMR spectra and elemental analysis. The antifungal activity of the obtained compounds has been determined against a number of clinic and fluconazole-resistant Candida strains by using microdilution method. Compounds (3a–3s) exhibited anticandidal activity in different ratios varying between the range of MIC: 50 and 200?µg/mL.     

Synthesis and antimicrobial activity of some new hydrazone-bridged thiazole-pyrrole derivatives

In this work, we synthesized fourteen different compounds which contain hydrazone bridged thiazole and pyrrole rings. For this purpose, pyrrole-2-carboxaldehydes were reacted directly with thiosemicarbazide in ethanol and then obtained thiosemicarbazones were condensed with α-bromoacetophenone derivatives (Hantzsch reaction) to give 1-substituted pyrrole-2-carboxaldehyde [4-(4-substituted phenyl)-1,3-thiazol-2-yl] hydrazones. The structures of the obtained compounds were elucidated by using IR, ¹H-NMR and FAB⁺-MS spectral data and elemental analyses results. All of the compounds were screened for their antibacterial and antifungal activities against twelve different microorganisms by using microbroth dilution method. Ketoconazole and chloramphenicol were used as standard drugs. All of the compounds showed good activity against Staphylococcus aureus and Enterococcus faecalis.     

Synthesis and Evaluation of Novel Metacetamol Derivatives with Hydrazone Moiety as Anticancer and Antimicrobial Agents

By exploiting the wide biological potential of the hydrazone scaffold, a series of hydrazone derivatives were synthesized, starting from N-(3-hydroxyphenyl)acetamide (metacetamol). The structures of the compounds were determined using IR, ¹H and ¹³C-NMR, and mass spectroscopic methods. The obtained molecules ( 3 a – j ) were evaluated for their anticancer potential against MDA-MB-231 and MCF-7 breast cancer cell lines. According to the CCK-8 assay, all tested compounds showed moderate to potent anticancer activity. Among them, N-(3-(2-(2-(4-nitrobenzylidene)hydrazinyl)-2-oxoethoxy)phenyl)acetamide ( 3 e ) was found to be the most effective derivative with an IC₅₀ value of 9.89 μM against MDA-MB-231 cell lines. This compound was further tested for its potential effects on the apoptotic pathway. Molecular docking studies was also carried out for 3 e in the colchicine binding pocket of tubulin. Additionally, compound 3 e also demonstrated effective antifungal activity, particularly against Candida krusei (MIC=8 μg/ml), indicating that nitro group at the 4^th position of the phenyl ring was the most preferable substituent for both cytotoxic and antimicrobial activity. Our preliminary findings suggest that compound 3 e could be exploited as a leading structure for further anticancer and antifungal drug development.     

Studies on hydrazone derivatives as antifungal agents

The increasing clinical importance of drug-resistant fungal pathogens has urged additional need to fungal research and new antifungal compound development. For this purpose, some N-(1-benzyl-2-phenylethylidene)-N′-[4-(aryl)thiazol-2-yl]hydrazone (1a-e) and N-(1-phenylbutylidene)-N′-[4-(aryl)thiazol-2-yl]hydrazone (2a-e) derivatives were synthesised and evaluated for antifungal activity. Their antifungal activities against standard and clinical strands of Candida albicans, Candida glabrata, Candida utilis, Candida tropicalis, Candida krusei, Candida zeylanoides, and Candida parapsilosis were investigated. A significant level of activity was observed.     

A sensitive determination of α-keto acids by gas-liquid chromatography and its application to the assay of l-glutamate dehydrogenase and aminotransferases

A sensitive and selective determination of α-keto acids was established by the use of a gas chromatograph equipped with an electron capture detector. α-Keto acids (pyruvic, oxaloacetic, α-ketobutyric, and α-ketoglutaric acids) were reacted with pentafluorophenylhydrazine, and the derivatives were extracted with ethyl ether, reacted with diazomethane, and were subjected to gas-liquid chromatography with an electron capture detector. In the course of the reaction, oxaloacetic acid was decarboxylated, and yielded pyruvic acid. In the case of pyruvic (oxaloacetic) and α-ketobutyric acids two peaks corresponding to the syn and anti forms of the hydrazone appeared, and in the case of α-ketoglutaric acid, two peaks corresponding to the hydrazone and the cyclization compound produced from the hydrazone. The sum of the two peaks was taken for the determination. The present method was applicable to the assay of l-glutamate dehydrogenase, aspartate: 2-oxoglutarate, and l-alanine: 2-oxoglutarate aminotransferases.     

N.m.r. studies of d-ribosylamines in solution: Derivatives of hydroxylamine,hydrazine, thiosemicarbazide,and secondary amines

N.m.r. spectroscopic studies (¹H, ¹³C) have shown that hydroxylamine and hydrazine react with 2,3-O-isopropylidene-d-ribofuranose (1) and d-ribose (2) to give primarily the acyclic oxime and hydrazone, respectively, whereas thiosemicarbazide affords mainly the cyclic pyranosyl and furanosyl derivatives. Acyclic or cyclic secondary amines, when condensed with either 1 or 2, furnished only mixtures of the β-pyranosyl and β-furansyl forms, and, in some reactions, Amadori rearrangement products (2–30%).     

Elimination of apple stem grooving virus by chemotherapy and development of an immunocapture RT-PCR for rapid sensitive screening

Ombuin (7,4′-dimethyl quercetin) (10 μg ml^-1, for 12 wk), glycyrrhizin/quercetin (80 μg ml^-1and 10 μg ml^-1respectively, for 18 wk), ribavirin (10 μg ml^-1, for 12 wk) and quercetin/ribavirin (10 μg ml^-1each, for 9–12 wk) reduced the titre of apple stem grooving virus (ASGV) when applied in vitro to infected tissue cultures of Nicotiana occidentalis obliqua Wheeler, and/or Malus domestica. ASGV was not detectable in both plant species after the quercitin/ribavirin treatment when tested by ISEM, herbaceous host indexing, RT-PCR, and immunocapture RT-PCR. A sensitive immunocapture RT-PCR procedure for the detection of ASGV was developed for the screening of treated samples to assess antiviral activity.     

Ribavirin targets eIF4E dependent Akt survival signaling

The eukaryotic translation initiation factor eIF4E is dysregulated in many cancers. eIF4E, through its mRNA export and translation functions, combinatorially modulates the expression of genes involved in Akt dependent survival signaling. For these activities, eIF4E must bind the 7-methyl guanosine (m⁷G) cap moiety on the 5′-end of mRNAs. We demonstrate that a physical mimic of the m⁷G cap, ribavirin, inhibits eIF4E dependent Akt survival signaling. Specifically, ribavirin impairs eIF4E mediated Akt activation via inhibiting the production of an upstream activator of Akt, NBS1. Consequently, ribavirin impairs eIF4E dependent apoptotic rescue. A ribavirin analog with distinct physico-chemical properties, tiazofurin, does not impair eIF4E activity indicating that only analogs that mimic the m⁷G cap will inhibit eIF4E function. Ribavirin represents a first-in-class strategy to inhibit eIF4E dependent cancers, through competition for m⁷G cap binding. Thus, ribavirin coordinately impairs eIF4E dependent pathways and thereby, potently inhibits its biological effects.     

Natural-product-based insecticidal agents 14. Semisynthesis and insecticidal activity of new piperine-based hydrazone derivatives against Mythimna separata Walker in vivo

In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, twenty-six new piperine-based hydrazone derivatives were synthesized from piperine, an alkaloid isolated from Piper nigrum Linn. The single-crystal structures of 6c, 6q and 6w were unambiguously confirmed by X-ray crystallography. Their insecticidal activity was evaluated against the pre-third-instar larvae of Mythimna separata Walker in vivo. Especially compounds 6b, 6i and 6r, the final mortality rates of which, at the concentration of 1 mg/mL, were 62.1%, 65.5% and 65.5%, respectively, exhibited more pronounced insecticidal activity compared to toosendanin at 1 mg/mL, a commercial botanical insecticide isolated from Melia azedarach. It suggested that introduction of the substituents at the C-2 position on the phenyl ring of the hydrazone derivatives was important for their insecticidal activity.