Synthesis of novel pyridazine derivatives as potential antimicrobial agents

A series of novel pyridazine derivatives incorporated with triazole, thiazolidine, imidazolidine, oxazine, and quinazoline moieties was synthesized by the reaction of [6-(4-phenoxyphenyl)pyridazin-3-yloxy]acetyl isothiocyanate with variety of nucleophilic reagents. The structures of all products were confirmed and characterized by the elemental analysis and spectroscopic studies (IR, MS, ¹H NMR). Also, the products were investigated for their antibacterial and antifungal activities and were compared with the standard drugs. Most of the synthesized compounds demonstrated potent to weak antimicrobial activity.     

Long-chain derivatives with a hexahydrothioxotetrazine moiety as potential antimicrobial agents

A series of hexahydrothioxotetrazine-containing compounds I–IV were evaluated for their antimicrobial activity. Fungi (Aspergillus sydowii, A. nidulari, A. terreus, Fusarium solanum, Trichoderma viridae, T. lignorum, Rhizopus arrhitus andCandida albicans) and bacteria (Escherichia coli, Salmonella sp.,Pseudomonas aeruginosa, bacillus sp.,Staphylococcus aureus, Klebsella sp.,Shigella sp. andStreptococcus faecalis) were used for this examination. Compounds I–III showed 90% growth inhibition against a large number of fungi. Two compounds (II and III) have shown significant antibacterial activity. The most striking feature of this study is that compound II, which does not carry an ester function, is the most potent antifungal and antibacterial agent. In general, these promising compounds may be of commercial significance in the future and therefore need developmental studies.     

Nano-TiO2 modified with 2-mercaptobenzimidazole as an efficient adsorbent for removal of Ag(I) from aqueous solutions

Nano-TiO₂ was modified with 2-mercaptobenzimidazole via surfactant activation and used as an adsorbent for the removal of Ag(I) under optimum conditions. The adsorbent was characterized using powder X-ray diffraction and FT-IR spectroscopy. The equilibrium data were fitted to the Langmuir, Freundlich and Temkin isotherm models. Langmuir isotherm describes the adsorption data better than Freundlich isotherm and Temkin. Kinetic studies showed that the pseudo second order kinetic model fits the adsorption kinetic processes well. Maximum adsorption capacity for Ag(I) was 128.2 mg g⁻¹ of nano-TiO₂. The method was successfully applied to the removal of silver from radiology film processing wastewater samples.     

银系抗菌剂的研发及其市场应用现状

总结了当前抗菌剂的分类,根据载体的不同,分别概述了当前不同类的银系抗菌剂的制备方法和研究现状,还报道了相关银系抗菌剂制备的专利技术,同时通过对银系抗菌剂市场的了解,对银系抗菌剂的市场应用现状作了相关报道。     

Chemoselective synthesis of phosphorus ylides through the reaction of 2-mercaptobenzimidazole and 2-hydroxybenzimidazole with triphenylphosphine and acetylenic esters

A one-step synthesis of dialkyl 2-(2-mercaptobenzimidazole-s-yl)-3-(triphenylphosphoranyliden) succinates and dialkyl 2-(2-hydroxybenzimidazole-n-yl)-3-(triphenylphosphoranyliden) succinates in fair yields are reported through the reaction of dialkyl acetylenedicarboxylates and triphenylphosphine in the presence of 2-mercaptobenzimidazole or 2-hydroxybenzimidazole.     

Synthesis and biological evaluation of acridine derivatives as antimalarial agents

New N‐alkylaminoacridine derivatives attached to nitrogen heterocycles were synthesized, and their antimalarial potency was examined. They were tested in vitro against the growth of Plasmodium falciparum, including chloroquine (CQ)‐susceptible and CQ‐resistant strains. This biological evaluation has shown that the presence of a heterocyclic ring significantly increases the activity against P. falciparum. The best compound shows a nanomolar IC₅₀ value toward parasite proliferation on both CQ‐susceptible and CQ‐resistant strains. The antimalarial activity of these new acridine derivatives can be explained by the two mechanisms studied in this work. First, we showed the capacity of these compounds to inhibit heme biocrystallization, a detoxification process specific to the parasite and essential for its survival. Second, in our search for alternative targets, we evaluated the in vitro inhibitory activity of these compounds toward Sulfolobus shibatae topoisomerase VI‐mediated DNA relaxation. The preliminary results obtained reveal that all tested compounds are potent DNA intercalators, and significantly inhibit the activity of S. shibatae topoisomerase VI at concentrations ranging between 2.0 and 2.5 μM .     

Synthesis and application of some new oxazole derivatives as antimicrobial agents

5-(p-Acetylphenyl)-2-phenyloxazole ( I ) was condensed with aromatic aldehydes to furnish chalcones 2a-e . Cyclocondensation of 2a-e with hydrazine hydrate and with phenyl hydrazine led to the formation of pyrazoline derivatives 3a-e and 4a-e respectively. Similarly, 2a was interacted with hydroxylamine to give isoxazoline ( 5 ). On the other hand, condensation of 1 with phenyl hydrazine yielded hydrazone 6 which on treatment with Vilsmeier reagent (DMF/POCl₃) gives 5-[p-(4-formyl-1-phenylpyrazol-3-yl)phenyl]-2-phenyloxazole ( 7 ). Also, a few derivatives of 7 have been prepared. Moreover, all compounds were screened for their antimicrobial activity against some strains of bacteria and fungi.     

Synthesis and biological evaluation of pyrazolylnaphthoquinones as new potential antiprotozoal and cytotoxic agents

The importance of American trypanosomiasis (Chagas' disease) in human pathology is widely known. The prognosis of this disease is poor and the choice of effective medicines limited, thus study of new drugs is absolutely necessary. In this work, the activities of three new pyrazolylnaphthoquinones, heterocyclic naphthoquinones bearing 3-aminopyrazole rings, were evaluated on Trypanosoma cruzi, the etiological agent of Chagas' disease. These activities were compared with those of three 5-aminoisoxazole analogues. In addition, since these compounds belong to a family of antiprotozoal and cytotoxic/antitumor agents, the activities of all six against Plasmodium falciparum, Trypanosoma brucei rhodesiense, and murine L-6 cells were also investigated. In the biological tests, five of the compounds showed significant in vitro trypanocidal activities against T. cruzi, with activities similar to that of benznidazole. Two of the 5-aminoisoxazole analogues also showed good activities, in one case highly selective, against the K1 and NF54 strains of P. falciparum (IC(50)<0.12 microg mL(-1)). Three of the compounds were cytotoxic to murine L-6 cells (IC(50)=0.21-0.50 microg mL(-1)). The results suggested that the three pyrazolylnaphthoquinones and one of the 5-aminoisoxazole analogues could be starting points for lead optimization programs against T. cruzi and P. falciparum, respectively.     

Simultaneous preconcentration of Cd(II), Cu(II) and Pb(II) on Nano-TiO2 modified with 2-mercaptobenzothiazole prior to flame atomic absorption spectrometric determination

Nano-TiO₂ modified with 2-mercaptobenzothiazole (MBT) was investigated as a new adsorbent for preconcentration of Cd(II), Cu(II) and Pb(II). The metal ions are adsorbed onto nano-TiO₂-MBT, eluted by nitric acid and determined by flame atomic absorption spectrometry. The parameters affecting the adsorption were investigated. Under optimized conditions, the calibration curves were linear in the range of 0.2–25.0, 0.2–20.0, and 3.0–70.0 ng mL⁻¹ for cadmium, copper and lead, respectively. The limits of detection for Cd(II), Cu(II) and Pb(II) were 0.12, 0.15 and 1.38 ng mL⁻¹, respectively. The method was applied to determination of Cd(II), Cu(II) and Pb(II) in water and ore samples.     

Synthesis of some novel 2-oxo-pyrano(2,3-b)- and 2-oxo-pyrido(2,3-b)quinoline derivatives as potential antimalarial,diuretic, clastogenic and antimicrobial agents

The 2-chloro-3-formyl quinoline derivatives ( 1a–e ) on treatment with acetic anhydride and sodium acetate, afforded the corresponding novel 2-oxo-pyrano(2,3-b) quinoline derivatives ( 2a–e ), and these were subjected to ammonia treatment to yield the corresponding naphthyridine derivatives ( 3a–e ). The prepared compounds ( 2a–e ) were tested for their antimalarial, diuretic, clastogenic and antimicrobial properties. Not all the compounds showed a diuretic effect and the significant increase in the frequency of micronuclei shows that they are non-clastogens, whereas the 7-chloro derivative ( 2e ) was a very effective antimalarial agent against the mosquito species. All the compounds were found to have optimum antimicrobial activity against Staphylococcus aureus, Escherichia coli and Salmonella typhi. Compounds 2d and 2e were found to be most active against the bacteria tested. © 1998 SCI     

Synthesis of aryl-substituted naphthalene-linked pyrrolobenzodiazepine conjugates as potential anticancer agents with apoptosis-inducing ability

A library of new aryl‐substituted naphthalene C8‐linked pyrrolo[2,1‐c][1,4]benzodiazepine (PBD) conjugates with various linker architectures were designed, synthesized, and evaluated for their anticancer activity against a panel of 11 human cancer cell lines. All 32 conjugates show anticancer potential, with some of them exhibiting particularly high activity (0.01–0.19 μM ). Thermal denaturation studies showed effective DNA binding capacity relative to DC‐81. In assays for biological activity relating to cell‐cycle distribution, these PBD conjugates induce G₀/G₁‐phase arrest and also cause an increase in the levels of p53 and caspase‐9 proteins, followed by apoptotic cell death. One conjugate in particular is the most promising candidate of the series, with the potential to be selected for further studies, either alone or in combination with existing anticancer therapies.     

5-甲氧基-2-巯基苯并咪唑合成新工艺

对以２ 硝基 ４ 甲氧基苯胺为原料合成５ 甲氧基 ２ 巯基苯并咪唑的工艺进行了如下改进：（１）将两步反应合并为“一锅炒”工艺,不需分离易氧化的中间体对 甲氧基邻苯二胺,革除了高真空蒸馏工艺;（２）环合时,用聚乙二醇催化,以水代乙醇作溶剂,变回流反应为（３０±５）℃保温反应,降低了成本。总收率７２％,比原分步工艺高１６％,目标产品纯化不需柱层析。     

A facile microwave enhanced synthesis of sulfur-containing 5-membered heterocycles derived from 2-mercaptobenzothiazole over ZnCl 2/DMF and antimicrobial activity evaluation

An efficient and extremely fast procedure for the synthesis of 4-thiazolidinones 4a–j by the reaction of arylidene-[(2-benzothiazolylthio)-acetamidyl] 3a–j with thioglycolic acid in DMF in the presence of a catalytic amount of anhydrous ZnCl ₂ under microwave irradiation is described. A considerable increase in the reaction rate has been observed with better yield in microwave technique. All the compounds have been screened for their antifungal activity against Candida albicans (ATCC-64550), Candida krusei (ATCC-14243) and Candida parapsilosis (ATCC-22019) and antibacterial activity against Escherchia coli (Gram?ve) (ATCC-8739), Staphylococcus aureus (Gram+ve) (ATCC-6538) and Bacillus substilis (Gram+ve) (ATCC-6633). The structures of the synthesised compounds 4a–j have been characterized on the basis of their elemental analysis and spectral data.     

Kinetic study of S-alkylation of 2-mercaptobenzimidazole by allyl bromide in the presence of potassium hydroxide

The S-alkylation (substitution on sulfur atom) of 2-mercaptobenzimidazole (MBI or ArSH) by allyl bromide (RBr) was successfully carried out in an aqueous solution of KOH/organic solvent two-phase medium. The reaction, which may take place either in the organic phase or on the interface, is greatly enhanced in the presence of KOH without the aid of quaternary salts as the catalyst to promote the reaction. No product was obtained from N-alkylation (substitution on nitrogen atom) during or after the reaction period by using a limited amount of allyl bromide (RBr) relative to that of MBI. Based on the experimental evidence, the kinetic behaviors and the characteristics of the reaction are sufficiently described by the pseudo-first-order rate law. The effects of the reaction conditions, including the agitation speed, the amount of KOH, volume of water, volume of dichloromethane, amount of allyl bromide, amount of 2-mercaptobenzimidazole, organic solvents and temperature on the conversion of allyl bromide and the apparent rate constants (k_app) were investigated in detail. Peculiar result is obtained in studying the effect of the volume of water on the conversion (or the reaction rate) in this work. Rational explanations are provided for the observed phenomena from experimental results.     

Synthesis of Potential Pharmaceutical Heterocycles as Surface Active Agents

Isoxazole, pyrazole, pyran, pyridine and pyrimidine derivatives of fatty acids were synthesized as surface and bioactive heterocycles. Hydroxylation of these intermediates by propylene oxide produced easy‐to‐handle, efficient and quickly biodegradable surface active agents, which revealed the importance of their applications in safety for humans as well as the environment. These compounds showed good activity against bacteria and fungi, showing promise in applications of drugs, cosmetics, and pesticides.     

Comparative electrochemical study of self-assembled monolayers of 2-mercaptobenzoxazole, 2-mercaptobenzothiazole, and 2-mercaptobenzimidazole formed on polycrystalline gold electrode

Comparative electrochemical behavior of self-assembled monolayers (SAMs) of three heteroaromatic thiols, 2-mercaptobenzoxazole (MBO), 2-mercaptobenzothiazole (MBT), and 2-mercaptobenzimidazole (MBI) are investigated by means of cyclic voltammetry and electrochemical impedance spectroscopy (EIS). The electrochemical characteristics of the electrode/solution interface are considerably and differently affected by thiols constructing the SAMs. The consumed charges for reductive desorption of SAMs, which is criterion for the amount of chemically adsorbed thiol, are significantly different for these three SAMs, specially for MBT, implying that SAM of MBT is formed through both sulfur atoms; the thiol sulfur and skeleton sulfur of the thiazole ring. Desorption potentials of the SAMs have shown the following order for strength of gold-sulfur bond: MBT > MBO > MBI. Activity of the three SAMs as pH-sensitive interfaces was also investigated and their surface-pK_a values derived from the EIS measurements showed this order for acidic strength of SAMs: MBO > MBT > MBI. This is the same order expected due to the difference in electronegativity of the O, S, and N heteroatoms, and confirms that the most electron-rich ring imidazole is attached to the benzene ring of MBI. A comparison of the interfacial charge transfer resistance variation as a function of gold immersion time in thiols solution reveals that kinetics of Au-MBT assembly is different from those of two others and confirms formation of Au-MBT SAM via both sulfur atoms of MBT.     

2-硝基查尔酮类衍生物的合成

在无溶剂条件下利用氢氧化钠和碳酸钾混合碱作为催化剂,使用研磨技术促进2-硝基苯甲醛和苯乙酮衍生物的固相羟醛缩合,得到了14种2-硝基查尔酮类衍生物。该法反应时间短,操作简便,收率好。     

Synthesis of novel poly 2‐vinylpyridine‐mixed metal complexes and studying their effect as antitumor chemotherapeutic agents,part 2

The poly2‐vinylpyridine and cationic polymer‐mixed metal complexes (P2VPMC) have been prepared and characterized by analytical measurement such as: molecular weight, elemental analysis, IR‐spectroscopy, NMR‐spectroscopy, XRD, and UV. The degree of N‐alkylation of poly vinyl pyridine (P‐2VP) was 10% determined by chlorine content according to elemental microanalysis. Through ICP instrument the complexation between P‐2VPC and the mixed metal chlorides was proven. The structure of the samples was characterized using X‐ray diffraction. It was found that the complexes have amorphous properties. The antitumor activity of this compound was examined in vitro on cell lines. The results reflect pronounced cytotoxicity of P‐2VPMC against animal experimental EAC cells line, and human, HeLa, HCT116 and Hep‐G2, cell lines. Antitumor activity of the novel compound as applied on mice bearing Ehrlich solid carcinoma, revealed delays tumor growth compared with untreated animals and decreases tumor volume. The antitumor activity of the P2VPMC might be due to its ability to pass through the membrane and interact with, DNA causing cross‐linking action which might be the key factor for great antitumor activity of the P2VPMC compound. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis of some new 3-(2′-heterocyclicethyl)-2-methyl-3,4-dihydroquinazolin-4-one derivatives as antimicrobial agents

3-(2′-Chloroethyl)-2-methyl-3,4-dihydroquinazolin-4-one was reacted with acetylacetone, ethyl acetoacetate and diethylmalonate in the presence of sodium ethoxide to afford the alkylation products IV, V and VI , Compounds IV, V and VI were reacted with hydrazine hydrate, phenylhydrazine, hydroxylamine hydrochloride, urea and thiourea to yield 3-(2′-heterocyclicethyl)-2-methyl-3,4-dihydroquinazolin-4-one derivatives VII-XV . The structures of the synthesized compounds were elucidated by elemental analyses and spectroscopic (IR and XH-NMR) analyses. The prepared compounds were tested for their antimicrobial activities in comparison with tetracycline as a reference compound.