Synthesis, spectral characterization and biological activity of zinc(II) complexes with 3-substituted phenyl-4-amino-5-hydrazino-1, 2, 4-triazole Schiff bases

New Zn(II) complexes have been synthesized by the reactions of zinc(II) acetate with Schiff bases derived from 3-substituted phenyl-4-amino-5-hydrazino-1, 2, 4-triazole and benzaldehyde, 2-hydroxyacetophenone or indoline-2,3-dione. All these complexes are soluble in DMF and DMSO; low molar conductance values indicate that they are non-electrolytes. Elemental analyses suggest that the complexes have 1:1 stoichiometry of the type [ZnL(H(2)O)(2)], [ZnL'(OAc)(2)(H(2)O)(2)] (L=dianionic Schiff bases derived from 3-(substituted phenyl)-4-amino-5-hydrazino-1, 2, 4-triazole and 2-hydroxyacetophenone or indoline-2,3-dione; L'=neutral Schiff bases derived from 3-(substituted phenyl)-4-amino-5-hydrazino-1, 2, 4-triazole and benzaldehyde) and they were characterized by FT-IR, (1)H NMR, (13)C NMR and FAB mass. All these Schiff bases and their complexes have also been screened for their antibacterial activities against Bacillus subtilis, Escherichia coli and antifungal activities against Colletotrichum falcatum, Aspergillus niger, Fusarium oxysporium and Carvularia pallescence by petriplates methods.     

二氢吲哚-2,3-二酮衍生物抑菌活性研究进展

二氢吲哚-2,3-二酮是一种结构简单且应用广泛的药物小分子,其衍生物的合成、结构和药理活性等备受关注。已有报道表明二氢吲哚-2,3-二酮具有抗菌、抗衰老、降血脂、抗癫痫、抗病毒等多种生物活性。本文主要围绕抑菌生物活性,对国内外关于二氢吲哚-2,3-二酮类化合物的构效关系进行分析总结,为后期该类新型抗菌化合物的设计合成提供参考。     

Coordination chemistry of palladium(II) and platinum(II) complexes with bioactive Schiff bases: Synthetic,spectral, and biocidal aspects

The Schiff bases, 5-nitro-indol-2,3-dionehydrazinecarboxamide (HSCZ¹) and 7-nitro-indol-2,3- dionehydrazinecarboxamide (HSCZ²), have been synthesized by the condensation of 5-nitro-indol-2,3-dione and 7-nitro-1H-indol-2,3-dione with semicarbazide hydrochloride, respectively. The palladium(II) and platinum( II) complexes have been prepared by mixing palladium chloride and platinum chloride in 1: 2 molar ratios with monobasic bidentate Schiff bases. The ligands and complexes of palladium and platinum have been characterized by elemental analyses, melting point determinations, conductance measurements, molecular weight determinations, and IR, ¹H NMR, and UV spectral studies. These studies showed that the ligands coordinate to the metal atoms in a monobasic bidentate mode, coordinating through oxygen and nitrogen donor systems. Thus, a tetracoordinated environment around the metal atom has been proposed. Both the ligands and their complexes have been screened for their biological activity on several pathogenic fungi and bacteria and were found to possess appreciable fungicidal and bactericidal properties. Plant growth regulating activity of one of the ligands and its complexes has also been recorded on gram plant, and results have been discussed. The article is published in the original.     

Synthesis and in vitro anticancer activity of some novel tetrahydroquinoline derivatives bearing pyrazol and hydrazide moiety

A new series of tetrahydroquinoline derivatives having pyrazol and hydrazide moieties were synthesized for the purpose of anticancer cell line evaluation. Syntheses of these compounds were firstly achieved by one pot four reactions. The reaction of 3-amino-tetrahydro-1H-pyrazolo [3,4-b]quinolin with aldehydes, indoline-2,3-dione derivatives to give 9a-c , 11a-c , and 13a,b , respectively. In similar manner for biological comparison, the reactions of compound 5 with the same aldehydes and indoline-2,3-dione derivatives to give 19a-c and 20a-c . The newly synthesized compounds were examined in vitro for their cytotoxic activity against HepG-2 and A549 cancer cells. The compounds 11a-c and 20a-c showed promising activity as anticancer agents against HepG-2 and A549 cancer cells.     

Electrochemical behavior and antioxidant activity of tetradentate Schiff bases and their copper(II) complexes

This study describes the effects of the substituents on electrochemical behavior and antioxidant activity of the six tetradentate Schiff bases, containing ethane-1,2-diamine or propane-1,2-diamine as the amine part and pentane-2,4-dione and/or 1-phenylbutane-1,3-dione as ??-diketone, and corresponding copper(II) complexes. Cyclic voltammograms of these compounds were recorded in dimethylsulfoxide and 0.1?M sodium perchlorate as supporting electrolyte with glassy carbon as working electrode at different scan rates. The voltammograms of Schiff bases alone showed only one irreversible peak. Voltammograms recorded for complexes showed the presence of quasi-reversible processes taking place at the metal center and reversible process at the ligand part. Both steric and inductive effects of substituents and structure of imine bridge of Schiff base ligands as well as complexes were discussed. These effects appear relevant for the antioxidant activity. Antioxidant activity of the investigated compounds expressed as Trolox equivalent antioxidant capacity is also discussed. The electrochemical behavior showed a high correlation with the antioxidant activity for investigated compounds.     

Engaging thieno[2,3-b]indole-2,3-dione for the efficient synthesis of spiro[indoline-3,4′-thiopyrano[2,3-b]indole] by reaction with N-substituted isatilidenes

A simple and efficient method, proceeding through a new mechanistic pathway, for the synthesis of spiro[indoline-3,4-thiopyrano[2.3-b]indole derivatives have been developed by exploiting the reaction of thieno[2,3-b]indole-2,3-dione with N-substituted isatilidenes. The compounds synthesized have been screened for antibacterial activity. The generality of the reaction and mechanistic rationale are presented.     

Acylation of α-SCF3 substituted β-carbonyl acetic acid and thiacetic acid derivatives with oxalyl chloride

α-CF₃S-substituted β-ketoacidamides, nitriles, thioamides and their Schiff bases are synthesised and their reactions with oxalyl chloride are investigated. As a new phenomenon the elimination of the CF₃S group during cylcisation to substituted 2,3,5-trioxo-1,4-oxazephine (7), 4-pyrroline-2,3-dione (9) and oxalyl (10) is observed. Factors influencing this course of the reaction and mechanism of product formation are discussed.     

Synthesis of new indole derivatives structurally related to donepezil and their biological evaluation as acetylcholinesterase inhibitors

New series of indole derivatives analogous to donepezil, a well known anti-Alzheimer and acetylcholinesterase inhibitor drug, was synthesized. A full chemical characterization of the new compounds is provided. Biological evaluation of the new compounds as acetylcholinesterase inhibitors was performed. Most of the compounds were found to have potent acetylcholinesterase inhibitor activity compared to donepezil as standard. The compound 1-(2-(4-(2-fluorobenzyl) piperazin-1-yl)acetyl)indoline-2,3-dione (IIId) was found to be the most potent.     

Unprecedented Multicomponent Reaction of Indoles,CS2 and Nitroarenes: Stereoselective Synthesis of (Z)-3-((Arylamino)methylene)indoline-2-thiones

An efficient method for the stereoselective synthesis of (Z)-3-((arylamino)methylene)indoline-2-thiones have been developed via a novel multicomponent reaction of indoles, CS₂ and nitroarenes. A range of functionalized indoline-2-thiones were prepared in moderate to good yields from easily available starting materials. The indoline-2-thione products can be easily derivatized to give biologically active thieno[2,3-b]indole and thiopyrano[2,3-b]indole skeletons in high yields.     

Design,Synthesis of New 1,2,4-Triazole/1,3,4-Thiadiazole with Spiroindoline,Imidazo[4,5-b]quinoxaline and Thieno[2,3-d]pyrimidine from Isatin Derivatives as Anticancer Agents

The current work aims to design and synthesis a new series of isatin derivatives and greatly enhances their cytotoxic activity. The derivatives 3-((bromophenyl) imino)-1-(morpholino (pyridine) methyl) indolin-2-one, 2-((oxoindoline) amino) benzoic acid, 3-(thiazolo-imino) indolinone, ethyl-2-((oxoindolin-3-ylidene)amino)-benzothiophene-3-carboxylate, 1-(oxoindoline)-benzo[4,5] thieno [2,3-d]pyrimidin-4(1H)-one, ethyl-2-(2-oxoindoline) hydrazine-1-carboxylate, N-(mercapto-oxo-pyrimidine)-2-(oxoindoline) hydrazine-1-carboxamide, N-(oxo-thiazolo[3,2-a] pyrimidine)-2-(oxoindolin-ylidene) hydrazine-carboxamide, 3-((amino-phenyl) amino)-3-hydroxy- indolinone, 3-((amino-phenyl) imino)-indolinone, 2-(2-((oxoindoline) amino) phenyl) isoindolinone, 2-(oxoindoline) hydrazine-carbothioamide, 5′-thioxospiro[indoline-3,3′-[1,2,4]triazolidin]-one, 5′-amino-spiro[indoline-3,2′-[1,3,4]thiadiazol]-2-one and 3-((2-thioxo-imidazo[4,5-b]quinoxaline) imino) indolinone were synthesized from the starting material 1-(morpholino (pyridine) methyl) indoline-2,3-dione and evaluated for their in vitro cytotoxic activity against carcinogenic cells. The new chemical structures were evidenced using spectroscopy (IR, NMR and MS) and elemental analysis. The results show that compounds imidazo[4,5-b]quinoxaline-indolinone, thiazolopyrimidine-oxoindoline, pyrimidine-oxoindoline-hydrazine-carboxamide, spiro[indoline-3,2′-[1,3,4] thiadiazol]-one and spiro[indoline-3,3′-[1,2,4]triazolidin]-one have excellent anti-proliferative activities against different human cancer cell lines such as gastric carcinoma cells (MGC-803), breast adenocarcinoma cells (MCF-7), nasopharyngeal carcinoma cells (CNE2) and oral carcinoma cells (KB).     

A new route to the synthesis of ellipticine quinone from isatin

1-(2-Oxo-2-(pyridin-4-yl)ethyl)indoline-2,3-dione can be prepared and converted by treatment with sodium hydroxide into 2-isonicotinoyl-1H-indole-3-carboxylic acid as a key intermediate which can be transformed into ellipticine quinone in a two step sequence.     

Formation of trialkyl quinoline-2,3,4-tricarboxylates by reaction of isatin, dialkyl acetylenedicarboxylates, and sodium O-alkyl carbonodithioates

An efficient one-pot synthesis of quinoline-2,3,4-tricarboxylates is described by reaction of isatin (indoline-2,3-dione) and electron-deficient acetylenic esters in the presence of sodium O-alkyl carbonodithioates, themselves prepared by addition of sodium hydride to a solution of an alcohol in CS₂.     

Isatins 3-C annulation vs ring-opening: Two different pathways for synthesis of spiro compounds via multicomponent reactions

An efficient synthesis of spiro compounds via two different pathways from the reactions of isatins, 3-phenylisoxazol-5(4H)-one (3-ethylisoxazol-5(4H)-one), and pyrazol-5-amine (6-aminopyrimidine-2,4(1H,3H)-dione) were reported. The catalyst Amberlyst-15 could be easy recycled and reused for many time without any appreciable loss in catalytic activity. The new type spiro compounds were gained through the ring-opening of isatins process. The structures of spiro[indoline-3,4′-isoxazolo[5,4-b]pyrazolo[4,3-e]pyridin]-2-one, spiro[isoxazolo[5,4-b]quino line-4,5′-pyrrolo[2,3-d]pyrimidine]-2′,4′,6′(1′H,3′H,7′H)-trione, and spiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-2,6′(5′H)-dione were successfully confirmed by ¹H NMR, ¹³C NMR, HRMS, and X-ray crystal diffraction analysis.     

α-(5—四唑基)氨基烃基膦酸酯的合成及其生物活性

合成了12个新的5—氨基—1H—1，2，3，4—四唑的Schiff碱，而后与亚磷酸 二乙酯反应，合成出了12个新的含四唑基的α-氨基烃基膦酸酯，通过IR，^1H NMR，^31P NMR和元素分析证实了它们的结构．生物活性实验证明，一些目标化合 物具有良好的植物生长调节活性，其中氯代苯甲醛和吲哚甲醛的Schiff碱生成的α -氨基烃基膦酸酯的生长素活性更好。     

Regio- and diastereoselective synthesis of anticancer spirooxindoles derived from tryptophan and histidine via three-component 1,3-dipolar cycloadditions in an ionic liquid

A small library of novel hybrid spiroheterocycles containing spirooxindole, pyrrolidine and indole/imidazole moieties were synthesized with complete regio- and diastereoselectively in good to excellent yields from a three-component process starting from a series of variously substituted (E)-(2-nitrovinyl)benzenes, indoline-2,3-dione derivatives and l-tryptophan or l-histidine in an ionic liquid. The key step of this transformation is a 1,3-dipolar cycloaddition reaction involving a rare class of in situ-generated azomethine ylides derived from aromatic amino acids. The compounds thus synthesized were evaluated for their anticancer activity and were shown to inhibit the proliferation of FaDu cells, a human epithelial cell line isolated from a squamous cell carcinoma of the hypopharynx, via apoptotic cell death.     

Synthesis and antileukemic activity of spiro[indoline-3,2′-thiazolidine]-2,4′-diones

A number of spiro[indoline-3,2′-thiazolidine]-2,4′-diones have been prepared via the cyclocondensation of isatin-3-imines with α-mercaptoacids. 1-Benzyl-5′,5′-dimethylspiro[indoline-3,2′-thiazolidine]-2,4′-diones were prepared by simultaneously refluxing 1-benzylisatin, α-mercaptoisobutyric acid and various anilines in toluene. 3′-(4-Chlorophenyl)-5,5′-dimethylspiro[indoline-3,2′-thiazolidine]-2,4′-dione was active in the P388 and the L1210 leukemia screen tests. A number of analogs of the active spiro compound have been prepared and submitted for antileukemic screening. Anticonvulsant screening results of related compounds are also included.     

Microwave-assisted synthesis and antibacterial activity of derivatives of 3-[1-(4-fluorobenzyl)-1H-indol-3-yl]-5-(4-fluorobenzylthio)-4H-1,2,4-triazol-4-amine

Herein, an excellent method for the synthesis of twelve novel Schiff base derivatives containing indole and triazole assisted by microwave irradiation is reported. Compared with the conventional method, the yields increased from 59–84 % to 85–96 % and the reaction time was reduced from 24–30 h to 4–8 min. Moreover, all series of the newly synthesized Schiff bases were evaluated for their antibacterial activity. The values of minimum inhibitory concentration (MIC) and IC50 indicated that many target compounds possessed excellent antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis.     

Novobiocin: redesigning a DNA gyrase inhibitor for selective inhibition of hsp90

Novobiocin is a member of the coumermycin family of antibiotics and is a well-established inhibitor of DNA gyrase. Recent studies have shown that novobiocin binds to a previously unrecognized ATP-binding site at the C-terminus of Hsp90 and induces degradation of Hsp90-dependent client proteins at approximately 700 microM. In an effort to develop more efficacious inhibitors of the C-terminal binding site, a library of novobiocin analogues was prepared and initial structure-activity relationships revealed. These data suggested that the 4-hydroxy moiety of the coumarin ring and the 3'-carbamate of the noviose appendage were detrimental to Hsp90 inhibitory activity. In an effort to confirm these findings, 4-deshydroxy novobiocin (DHN1) and 3'-descarbamoyl-4-deshydroxynovobiocin (DHN2) were prepared and evaluated against Hsp90. Both compounds were significantly more potent than the natural product, and DHN2 proved to be more active than DHN1. In an effort to determine whether these moieties are important for DNA gyrase inhibition, these compounds were tested for their ability to inhibit DNA gyrase and found to exhibit significant reduction in gyrase activity. Thus, we have established the first set of compounds that clearly differentiate between the C-terminus of Hsp90 and DNA gyrase, converted a well-established gyrase inhibitor into a selective Hsp90 inhibitor, and confirmed essential structure-activity relationships for the coumermycin family of antibiotics.     

Effects of Coumarinyl Schiff Bases against Phytopathogenic Fungi,the Soil-Beneficial Bacteria and Entomopathogenic Nematodes: Deeper Insight into the Mechanism of Action

Coumarin derivatives have been reported as strong antifungal agents against various phytopathogenic fungi. In this study, inhibitory effects of nine coumarinyl Schiff bases were evaluated against the plant pathogenic fungi (Fusarium oxysporum f. sp. lycopersici, Fusarium culmorum, Macrophomina phaseolina and Sclerotinia sclerotiourum). The compounds were demonstrated to be efficient antifungal agents against Macrophomina phaseolina. The results of molecular docking on the six enzymes related to the antifungal activity suggested that the tested compounds act against plant pathogenic fungi, inhibiting plant cell-wall-degrading enzymes such as endoglucanase I and pectinase. Neither compound exhibited inhibitory effects against two beneficial bacteria (Bacillus mycoides and Bradyrhizobium japonicum) and two entomopathogenic nematodes. However, compound 9 was lethal (46.25%) for nematode Heterorhabditis bacteriophora and showed an inhibitory effect against acetylcholinesterase (AChE) (31.45%), confirming the relationship between these two activities. Calculated toxicity and the pesticide-likeness study showed that compound 9 was the least lipophilic compound with the highest aquatic toxicity. A molecular docking study showed that compounds 9 and 8 bind directly to the active site of AChE. Coumarinyl Schiff bases are promising active components of plant protection products, safe for the environment, human health, and nontarget organisms.     

Coordination chemistry of oxovanadium(V) complexes with active Schiff bases: synthetic,spectral, and antimicrobial approach

The Schiff bases, 3-(indolin-2-one)hydrazinecarbothioamide (L¹H), 3-(indolin-2-one)hydrazinecarboxamide (L²H), 5,6-dimethyl-3-(indolin-2-one)hydrazinecarbothioamide (L³H), and 5,6-dimethyl-3-(indolin-2-one)hydrazinecarboxamide (L⁴H), have been synthesized by the condensation of ¹ H-indol-2,3-dione and 5,6-dimethyl-1H-indol-2,3-dione with the corresponding hydrazinecarbothioamide and hydrazinecarboxamide, respectively. The complexes of oxovanadium and ligands have been characterized by elemental analyses, melting points, conductance measurements, molecular weight determinations, and IR, ¹H NMR and UV spectral studies. These studies showed that the ligands coordinated to the oxovanadium in a monobasic bidentate fashion through oxygen or sulfur and the nitrogen donor system. Thus, penta-and hexacoordinated environment around the vanadium atom has been proposed. All the complexes and their parent organic moieties have been screened for their biological activity on several pathogenic fungi and bacteria and were found to possess appreciable fungicidal and bactericidal properties. The article was submitted by the authors in English.