Synthesis,characterization and antimicrobial study via new heterocyclic derivatives of trimethoprim

New compounds of trimethoprim heterocyclic derivatives were synthesized. These compounds were synthesized through the condensation reaction between trimethoprim with bromoacetic acid to yield compound 1. Several Schiff bases 2–7 have been synthesized by the condensation different aromatic aldehydes with compound 1. Compound 8 were formed from the reaction of sodium nitrite and acetyl acetone in presence of conc. hydrogen chloride to obtain the hydrazono derivative; then, Cyclocondensation of compound 8 with hydrazine hydrate, phenyl hydrazine and dinitrophenyl hydrazine respectively to yield compounds 9–11 in ethanol affording the pyrazoline derivatives. This work involves the synthesis of some 1,2,3-Triazoles derived from compound 1 by the action of sodium azide on the diazonium chloride salt to yield 5-azido-8-(3,4,5-trimethoxybenzyl)imidazo[1,2-c]pyrimidin-3(2H)-one 12. Finally, by reaction of 12 with acetyl acetone and ethyacetoacetate; respectively in sodium ethoxide/ethanol as a solvent to form compounds 13, 14. The structures of the compounds 1–14 were characterized by elemental analysis, spectral data and antimicrobial evaluation of the some newly synthesized compounds and found that the synthesized compounds are active against tested Gram positive and Gram negative bacteria like Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Proteus.     

Synthesis and antimicrobial evaluation of some heterocyclic chalcone derivatives

Some new heterocyclic compounds containing isoxazole, pyrazole and oxadiazole ring systems were prepared from various chalcones. The synthesized compounds have been characterized by elemental analysis and spectral methods. These compounds were screened for their antimicrobial activities.     

5-(3-吲哚基)亚甲基噻唑烷-2,4-二酮衍生物的合成及体外抗肿瘤活性探索

将N-取代吲哚-3-甲醛和2,4-噻唑烷二酮通过亚甲基键合,再对噻唑烷二酮氮取代,合成了一系列5-(3-吲哚基)亚甲基噻唑烷-2,4-二酮衍生物(e1-e9).采用IR,1H NMR和HRMS对其结构进行了表征;采用MTT法对目标物抑制5种癌细胞增殖活性进行了测试.结果表明,所有目标物对A549、HCT116和PC-9表现出抑制活性,其中吲哚氮被苄基取代的化合物e1和e3对测定的癌细胞增殖抑制活性与5-氟尿嘧啶(5-FU)相近,并且对A549和HCT116表现出中等的抑制活性(IC50<30μM)。     

Antitumor,cytotoxic, and antioxidant evaluation of six heterocyclic compounds containing different heterocycle moieties

Heterocyclic compounds with different heterocycle moieties, namely benzoxazinone, benzimidazole, quinazolinone, and benzofuranone heterocyclic rings, were synthesized, characterized, and evaluated for their anticancer activity against human hepatocellular carcinoma cell line (HepG2) using sulforhodamine B (SRB) and dimethylthiazol-diphenyltetrazolium bromide (MTT) assays. Also, their cytotoxic activities were tested against human epithelioid carcinoma (Hela) cell line in comparison with normal cell, amniotic epithelial (WISH) cell line, as an in vitro toxicity estimation model. The results showed clearly that 2-(2-benzyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide 4 is the most potent antioxidant and anticancer agents. Although, 3-amino-2-benzylquinazolin-4(3H)-one 5 is less potent anticancer agent against Hela but it is more safe against normal cell (WISH).     

Synthesis,characterization, antioxidant properties and DFT calculation of some new pyrimidine derivatives

Abstract

In this study, 5-benzoyl-4-(4-(methylthio)phenyl)-6-phenyl-1,2,3,4-tetrahydro-2-thioxo (1), oxo (2) and imino (3) pyrimidine derivatives were prepared via Multicomponent Cyclocondensation Reactions (MCRs). The compounds thiazolo[3,2-a]pyrimidin-3(5H)-one (4) and thiazin-4(6H)-one (5) were obtained via the reaction of compound 1 with bromoacetic acid and 3-bromopropionic acid, respectively. Structures were determined by using FT-IR, ¹H/¹³C NMR and elemental analyses. Also the compounds 4 and 5 were analyzed by X-ray single crystal analysis. All compounds were investigated as corrosion inhibitors using density functional theory (DFT) at the level of B3LYP/6-31G (d, p). According to the calculations, the compound 3 appears to be a good inhibitor for corrosion. On the other hand, total antioxidant properties were measured in vitro by DPPH^?, ABTS^?+ test, hemolysis of phenylhydrazine erythrocytes and metal chelating effect. The results were compared with standard antioxidants such as trolox and α-tocopherol. These data revealed that compounds 1, 2 and 5 are more active with respect to 3 and 4 in scavenging the radicals.     

Synthesis,anti-hyperglycaemic activity,and in-silico studies of N-substituted 5-(furan-2-ylmethylene)thiazolidine-2,4-dione derivatives

Thiazolidinedione derivatives have been used as anti-hyperglycemic agents in diabetic patients since last decade. In the present study, a series of N-substituted-5-(furan-2-ylmethylene)thiazolidine-2,4-dione derivatives were synthesized and characterized by ¹H-NMR, ¹³C-NMR and mass spectra. The introduction of the alkyl/haloalkyl moiety onto the amidic nitrogen of the thiazolidine-2,4-dione ring was intended to enhance the anti-hyperglycaemic activity, which was further tested in vivo by using alloxan-induced diabetic laca mice. Molecular docking simulation studies further helped in understanding the nature of the interactions and the binding mode of ligands inside the active site of the protein tyrosine phosphatase 1B enzyme, which negatively regulates the insulin signaling pathway. The compounds were screened for in-vivo anti-hyperglycaemic activity in which compounds 9 and 10 have exhibited significant decreases in blood glucose level comparable to that of pioglitazone.

     

In vitro cytotoxic evaluation of some new heterocyclic sulfonamide derivatives

Sulfonamide‐bearing compounds posses many types of biological activities and have been recently reported to show substantial antitumor activity in vitro and/or in vivo. There are a variety of mechanisms for the anticancer activity, and the most prominent mechanism is the inhibition of carbonic anhydrase isozymes. This work reports the synthesis of some new quinoline, pyrimido[4,5‐b]quinoline and 3,1‐oxazinoquinoline derivatives bearing a sulfonamide moiety. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against Ehrlich ascites carcinoma cells. Compounds 10 , 13 , and 26 were the most active compounds with IC₅₀ values of 6.1 μM, 6.8 μM, and 6.4 μM, respectively, and exhibited better activities than the reference drug doxorubicin (IC₅₀ = 68.1 μM). J. Heterocyclic Chem., 2011.     

Synthesis,characterization and antimicrobial evaluation of novel halopyrazole derivatives

Two novel halopyrazole derivatives (3, 5) were synthesized from 5-chloro-3-methyl-1-phenylpyrazole-4-carboxaldehyde (1) using appropriate synthetic routes. Newly synthesized compounds were characterized using elemental analysis, spectral data (IR, ¹H NMR, ¹³C NMR and mass spectrometry) and were evaluated for their in vitro antimicrobial activity. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC) were determined for the test compounds as well as for reference standards. The investigation of antimicrobial screening revealed that compounds (3, 5) showed good antibacterial and antifungal activities, respectively.     

Synthesis,characterization and antimicrobial activities of new bis-hydrazonothioxothiazolidinone derivatives

New bis-hydrazonothioxothiazolidinone derivatives based on 2-thioxothiazolidin-4-one were synthesized in good yields using a simplified experimental condition. The structure of synthesized compounds was established with the help of common physico-chemical analysis and various spectroscopic techniques like FT-IR, mass and ¹H NMR. The results of characterizations are in good agreement with the proposed structure of all the synthesized compounds. Further, the antimicrobial (antibacterial and antifungal) activities of all the synthesized derivatives were carried out against various species like Bacillus subtilis, Escherichia coli, Aspergillous niger and Aspergillous flavus by using agar-cup method. The results of antimicrobial screening showed that all the compounds have mild to moderate activity. However, some of the compounds (3a, 3b, 3d, 3e, 3f, 3g, 3i and 3j) have shown better activity than the other.     

Synthesis,characterization, and antimicrobial activity of new benzofuran derivatives

Russian Journal of General Chemistry - A novel series of (5-substituted-1-benzofuran-2-yl)(2,4-substituted phenyl)methanones (4a–4i) have been prepared by the Knoevenagel condensation of...     

Molecular docking studies of some new imidazole derivatives for antimicrobial properties

In modern drug designing, molecular docking is routinely used for understanding drug-receptor interaction. In the present study six imidazole derivatives containing substituted pyrazole moiety (2a,b and 4a–d) were synthesized. Structures of the newly synthesized compounds were characterized by spectral studies. Compounds were screened for their antibacterial activity. Compound 4c was found to be potent antimicrobial against Pseudomonas aeruginosa at concentrations of 1 and 0.5 mg/mL compared to standard drug Streptomycin. All the compounds were subjected to molecular docking studies for the inhibition of the enzyme l-glutamine: d-fructose-6-phosphate amidotransferase[GlcN-6-P] (EC 2.6.1.16). The in silico molecular docking study results showed that, all the synthesized compounds having minimum binding energy and have good affinity toward the active pocket, thus, they may be considered as good inhibitor of GlcN-6-P synthase.     

Synthesis and biological evaluation of optically active 3-H-1-carbacephem compounds

3-H-1-Carbacephem nuclei with or without a 2 alpha- or 2 beta-methyl group were prepared via 2 + 2 cycloaddition followed by intramolecular Horner-Emmons cyclization. Optically active 3-H-1-carbacephem compounds were efficiently prepared by employing a penicillin acylase-producing microorganism in two ways. That is, the 7-phenylacetamide of a racemic carbacephem nucleus was hydrolyzed enantioselectively with the enzyme to afford the optically pure nucleus, which was then acylated to give antimicrobial compounds. Alternatively, a racemic carbacephem nucleus was directly and enantioselectively phenylglycylated with the enzyme. 3-H-1-Carbacephem nuclei appeared to be better substrates for penicillin acylase than penam or cephem nuclei of natural origin. 3-H-1-Carbacephem compounds showed potent antimicrobial activity; compound 32a exhibited activity comparable to that of ceftizoxime, a cephem analog with the same acyl group. It is of interest that the 3-H-1-carbacephem compound turned out to have more potent antimicrobial activity than its 3-substituted methyl analog.     

Synthesis,antimicrobial, antiquorum-sensing and cytotoxic activities of new series of benzothiazole derivatives

New series of benzothiazole derivatives were designed and synthesized. The newly synthesized compounds were screened for their antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus cereus. Compounds 6j and 6o showed the highest activity against E. coli and S. aureus. The antifungal activity of these compounds was also tested against Candida albicans and Aspergillus fumigatus293. Compounds 4c, 4g and 6j exhibited the highest activity against C. albicans. In addition, compounds4 a and 6j displayed promising activity against A. fumigatus 293. The same compounds were examined for their antiquorum-sensing activity against Chromobacterium violaceum ATCC 12472, whereas compounds4 a, 6j and 6p showed moderate activity. The in vitro cytotoxicity testing of the synthesized compounds was performed against cervical cancer(Hela) and kidney fibroblast cancer(COS-7) cell lines. Results indicated that all tested compounds have IC50 values 50 mmol/L against both cell lines. Molecular properties, toxicities, drug-likeness, and drug score profiles of compounds 4a–c, 5a, 6g,h, 6j, 6l, 6o and7 c,d were also assessed.     

Research on heterocyclic compounds. XX. Synthesis of trifluoromethyl derivatives of fused imidazole systems

A series of heterocyclic compounds having an imidazole ring fused with another ring with a bridgehead nitrogen atom and bearing a trifluoromethyl moiety was synthesized by reaction of 3-bromo-1,1,1-trifluoroacetone with various heteroarylamines. In some cases, an intermediate compound obtained together with the required product was isolated and its structure was elucidated: e.g., starting from 2-aminopyridine we have obtained 2-trifluoromethylimidazo[1,2-a]pyridine and 2-hydroxy-2-trifluoromethyl-2,3-dihydro-1H-imidazo [1,2-a]pyridinium bromide. Such results confirmed the mechanism previously proposed for this reaction.     

Synthesis and structure of heterocyclic compounds. 1-Amino-2,4-Disubstituted imidazoles

A synthesis of 1-aminoimidazoles by reaction between α-halogenoketones and N-acetylamidrazones is described. Structure and position of substituent groups in the synthesized aminoimidazoles were established by spectroscopical methods.     

Synthesis,characterization and antimicrobial evaluation of 2,5-disubstituted-4-thiazolidinone derivatives

In the present study novel derivatives of 4-thiazolidinone were prepared from biphenyl-4-carboxylic acid and evaluated for their in vitro antimicrobial activity against two Gram negative strains (Escherichia coli and Pseudomonas aeruginosa) and two Gram positive strains (Bacillus subtilis and Staphylococcus aureus) and fungal strain Candida albicans and Aspergillus niger. The newly synthesized compounds were characterized by IR, ¹H NMR and C, H, N analyses. The results revealed that all synthesized compounds have a significant biological activity against the tested microorganisms. Among the synthesized derivatives 4g (biphenyl-4-carboxylic acid [2-(3-bromophenyl)-5-(3-nitrobenzylidene)-4-oxo-thiazolidin-3-yl]-amide) and 4i (biphenyl-4-carboxylic acid [5-(3-bromobenzylidene)-2-(3-bromophenyl)-4-oxo-thiazolidin-3-yl]-amide) were found to be most effective antimicrobial compounds.     

Synthesis and cytotoxic evaluation of new colchicine derivatives bearing 1, 3, 4-thiadiazole moieties

In search of novel anticancer agents, a series of N-methyl colchiceinamide derivatives (7a-7i) containing 1,3,4-thiadiazole moieties were synthesized, and their structures were confirmed by spectral analysis. Cytotoxicity of these compounds was evaluated by MTT assay in vitro against four human tumor cell lines, i.e. A2780, A549, BEL7402, and MCF-7. The results indicated that most of the derivatives showed significant anticancer activities, particularly, compounds 7h and 7i showed more potent cytotoxic activities of all screened cancer cells than colchicine.     

Synthesis,characterization, and antimicrobial evaluation of some novel anthracene heterocycles derivatives

A series of novel heterocyclic compounds containing anthracene moiety was synthesized. Reaction of (11R,15S)-9,10-dihydro-9,10-[3,4]furanoanthracene-12,14-dione with 2-cyanoacetohydrazide gave 2-cyano-pyrroloanthracen acetamide (1) , which acts as an adaptable material for the synthesis of new heterocyclic compounds. The synthesized compounds were examined for their antimicrobial activity against Escherichia coli and Staphylococcus aureus via p-iodonitrotetrazolium violet formazon assay. The results exhibited great activity against the tested strains with a minimum bactericidal concentration range from 0.636 to 3.8 mg/mL) and 0.159 to 3.6 mg/mL for E coli and S aureus, respectively. Interestingly, the highest activity was recorded for chromene derivative (6) against both strains.