Synthesis and Antimicrobial Activity of Some New 4H-Pyrrolo[1,2-a]benzimidazoles

Some new 4H-pyrrolo[1,2-a]benzimidazoles（2a-2f） have been synthesized. The structures of these compounds were confirmed by IR, tH NMR, mass spectroscopy and elemental analysis. Compound 2a was further confirmed by X-ray diffraction. The in vitro antimicrobial activities of these compounds were determined against some gram-positive bacteria, gram-negative bacteria and fungi and their drug-resistant isolates in comparison with standard drugs. Antimicrobial results indicate that compounds 2c, 2d and 2e show moderately active antibacterial properties, their minimum inhibitory concentrations are from 12.5 μg/mL to 125 μg/mL. In the series, the most active compound against C. albicans is compound 2fwith an MIC value of 31.25 μg/mL.     

Synthesis and antitumor activity of some new pyrazolo[1,5-a] pyrimidines

New series of pyrazolo[1,5-a]pyrimidine derivatives 7a-i, 11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines, namely colorectal carcinoma (HCT116), prostate adenocarcinoma (PC-3) and liver carcinoma (HepG-2) using MTT cytotoxicity assay at 100 μg/mL. Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells. Whereas, compounds 7d and 11a showed better antitumor activity than the rest of the compounds against both cell lines. A structure-activity relationship (SAR) has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data (MS, IR, ¹H NMR and ¹³C NMR) and elemental analysis.     

Synthesis and Antitubercular Evaluation of N‐Arylpyrazine and N,N′‐Alkyl‐diylpyrazine‐2‐carboxamide Derivatives

Two series of pyrazinamide (PZA) derivatives have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. Some compounds exhibited minimum inhibitory concentration activity of 50–100 μg/mL, greater than the first line antituberculosis drug PZA in Alamar Blue assay (>100 μg/mL). The obtained activities can be considered promising results, which characterizes these compounds as good start points to development of new antitubercular agents.     

Synthesis and Antimicrobial Evaluation of 1,4-Naphthoquinone Derivatives as Potential Antibacterial Agents

1,4-Naphthoquinones are an important class of compounds present in a number of natural products. In this study, a new series of 1,4-naphthoquinone derivatives were synthesized. All the synthesized compounds were tested for in vitro antimicrobial activity. In this present investigation, two Gram-positive and five Gram-negative bacterial strains and one pathogenic yeast strain were used to determine the antibacterial activity. Naphthoquinones tested for its antibacterial potencies, among seven of them displayed better antimicrobial activity against Staphylococcus aureus (S. aureus; 30–70 μg/mL). Some of the tested compounds showed moderate to low antimicrobial activity against Pseudomonas aeruginosa (P. aeruginosa) and Salmonella bongori (S. bongori; 70–150 μg/mL). In addition, most active compounds against S. aureus were evaluated for toxicity to human blood cells using a hemolysis assay. For better understanding, reactive oxygen species (ROS) generation, time-kill kinetic study, and apoptosis, necrosis responses were investigated for three representative compounds.     

一些吲哚二酮类衍生物的合成及对AHAS的抑制活性

基于一些新结构特征的AHAS抑制剂, 设计并合成了一系列吲哚二酮类化合物. 初步的生物活性测试结果表明, 所合成的化合物在体内和体外均具有一定的生物活性, 其中, 化合物13在100 μg/mL浓度下对AHAS的抑制达到85%, 化合物7(平皿法)在100 μg/mL浓度条件下对油菜胚根生长抑制率可达84.7%, 是一类未见文献报道的结构新型的AHAS抑制剂, 有望为进一步设计合成更高活性的化合物提供参考.     

Synthesis and bioactivity of beta-carboline derivatives

The beta-carboline alkaloids possess a wide diversity of important biochemical effects and pharmacological properties. A series of beta-carboline derivatives were synthesized from L-tryptophan through the Pictet-Spengler reaction and oxidation of K2Cr2O7 by a sequential one-pot synthesis method. In vitro anti-bacterial, insecticidal, and cytotoxic activities of all synthesized compounds were investigated by the tablet diffusion, leaf disc, and MTT methods, respectively. Some of the compounds (1-1, 1-2, 1-3 and 1-12) exhibited obvious anti-bacterial effects and some (1-3) had significant cytotoxic activities against tumor cells 3LL, MCF-7, BGC-823 and QGY-7701, with IC50 values of 7.79, 5.75, 3.53 and 4.02 microg/mL, respectively. No insecticidal activity against third stage instar larvae of Mythimna separata Walker were observed under the tested concentration.     

Synthesis, characterization, and antimicrobial evaluation of oxadiazole congeners

A series of 1,3-oxazole, 1,3-thiazole, isomeric 1,2,4-oxadiazole, 1,3,4-oxadiazole, and 1,2,3,4-tetrazole heterocycles was synthesized. All the compounds shared as a common feature the presence of a 4-hydroxyphenyl substituent. The structures of the synthesized compounds were confirmed by MS, 1H-NMR, and elemental analysis. In vitro antimicrobial activity for all the newly synthesized compounds at concentrations of 200-25 μg/mL was evaluated against Gram+ve organisms such as methicillin-resistant Staphylococcus aureus (MRSA), Gram-ve organisms such as Escherichia coli (E. coli), and the fungal strain Aspergillus niger (A. niger) by the cup plate method. Ofloxacin and ketoconazole (10 μg/mL) were used as reference standards for antibacterial and antifungal activity, respectively. Compounds 15, 16, and 20 showed notable antibacterial and antifungal activities at higher concentrations (200 μg/mL), whereas 17-19 were found to display significant antibacterial or antifungal activity (25-50 μg/mL) against the Gram+ve, Gram-ve bacteria, or fungal cells used in the present study.     

Synthesis and anti‐HIV activity of new chiral 1,2,4‐triazoles and 1,3,4‐thiadiazoles

5‐substituted 4‐(4‐chlorophenyl)‐4H‐1,2,4‐triazol‐3‐thiones 3 and 2‐substituted 5‐(4‐chlorophenylamino)‐1,3,4‐thiadiazoles 4 were prepared from the intermediate thiosemicarbazides 2 under basic and acidic conditions, respectively. The thiosemicarbazides, in turn, were prepared by the reaction of hydrazides 1 with 4‐chlorophenylisothiocyanate in MeOH. Some of the new synthesized compounds were assayed against HIV‐1 and HIV‐2 in MT‐4 cells. All the compounds were inactive except 3f , which showed an EC₅₀ value of 23.9 μg/mL and 9.9 μg/mL against HIV‐1 and HIV‐2 with a therapeutic index of 3 and 7, respectively. It means that compound 3f was cytotoxic to MT‐4 cells at CC₅₀ of 72.7 μg/mL in both strains. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:316–322, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20282     

Synthesis,Crystal Structure and Biological Activites of Rotenone O-Alkyl Oximes

A series of rotenone O-alkyl oxime derivatives was designed and synthesized. Their structures were confirmed by elemental analyses, Fourier transform infrared(FTIR) and ¹H NMR spectral studies, and the typical crystal structure of rotenone O-ethyl oxime(3b) was determined by X-ray diffraction. The preliminary biological activities of the new compounds were evaluated. The results of bioassays indicate that the title compounds exhibit moderate insecticidal and bactericidal activities. Among the synthesized compounds, compound 3q exhibited 90.0% mortality against M. separata at 1000 μg/mL. Compounds 3b and 3g exhibited both 90.0% inhibition rate against R. solani at 500 μg/mL, respectively.     

Synthesis and bioactivities of novel 2-(thioether/sulfone)-5-pyrazolyl-1,3,4-oxadiazole derivatives

By introducing the pyrazole moiety into the 5-position of 1,3,4-oxadiazole,a series of novel 2-(thioether/sulfone)-5-pyrazolyl-l,3,4-oxadiazole derivatives were synthesized.Preliminary bioassays suggested that target compounds exhibited appreciable activity against pathogenic bacteria Xanthomonas oryzae pv.oryzae(Xoo) and five phytopathogenic fungi in vitro.Among them,the half-maximal effective concentration(EC_(50)) values of 6c,7a,7b and 7c against Xoo were within 16.6 μg/mL and 65.7 μg/mL,which were better than those of commercial agricultural antibacterial bismerthiazol(92.6 μg/mL) and thiodiazole copper(121.8 μg/mL).While compounds 7a,7b,and 7c exerted comprehensive antifungal activity toward five plant fungi,which were comparable with that of hymexazol.The results demonstrated that this kind of compounds can be further studied and developed as promising antifungal and antibacterial agents.     

Design,Ultrasonic-assisted Synthesis and Evaluation In vitro Antimicrobial Activity of Bis-isoxazole Derivatives Bearing Chloro-pyridinyl Group

An ultrasonic-assisted synthesis of bis-isoxazole derivatives was developed. Eight 3-(6-chloropyridin-3-yl)-5-{[(3-aryli-soxazol-5-yl)methoxy]methyl}isoxazoles were synthesized by 1,3-dipolar cycloaddition reaction between substituted isoxazolyl alkyne compounds and 6-chloro-N-hydroxynicotinimidoyl chloride. The structures of the synthesized compounds were confirmed by HRMS, FTIR, ¹H and ¹³C NMR spectroscopy. Wherein, the antifungal and antibacterial activities of target compounds were tested. The synthesized compounds 6a and 6h exhibited better antifungal activity in comparison with the standard drug itraconazole. The minimum inhibitory concentrations(MICs) of both compound 6a and compound 6h were both 4 μg/mL against Candida albicans ATCC 10231.     

Design, synthesis and biological evaluation of hydroxamic acid derivatives as potential high density lipoprotein (HDL) receptor CLA-1 up-regulating agents

Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) were reported in our recent publication as novel human high density lipoprotein (HDL) receptor CD36 and Lysosomal integral membrane protein-II Analogous-1 (CLA-1) up-regulators. As part of a broader effort to more fully explore the structure-activity relationships (SAR) of CLA-1 up-regulators, we synthesized a series of hydroxamic acid derivatives and evaluated their CLA-1 up-regulating activities in HepG2 cells. Some compounds exhibited over 10-fold up-regulation of CLA-1 expression in HepG2 cells at 10 μg/mL concentration. The compound 1g showed the best potency, with a lower EC(50) than TSA (EC(50) = 0.32 μM versus 1.2 μM). These compounds provide early new CLA-1 up-regulators with potential for treating atherosclerosis.     

Synthesis of novel tetra-substituted benzimidazole compounds containing certain heterostructures with antioxidant and anti-urease activities

A new series of 5,6-dimethyl-2-phenyl-1H-benzimidazole derivatives was synthesized. The antioxidant activities of the synthesized compounds were determined according to the cupric reducing antioxidant capacity (CUPRAC), ABTS, and DPPH assays. Many of the target compounds showed good antioxidant activity. Among these compounds, it has been determined that the carbothioamide and 1,2,4-triazole derivatives had a very good antioxidant capacity. Also, all compounds were screened for in vitro inhibitory activity against Jack bean urease. Among the synthesized molecules, the starting compound, acetate, and acetohydrazide derivatives (with IC₅₀ values 12.02, 11.40, and 8.04 μg/mL, respectively) had a higher inhibitory effect on urease and exhibited a lower IC₅₀ values than acetohydroxamic acid (IC₅₀: 20.50 μg/mL) and thiourea (IC₅₀: 14.04 μg/mL) as a reference inhibitors.     

Synthesis and antifungal activity of novel sulfone derivatives containing 1,3,4-oxadiazole moieties

A series of new sulfone compounds containing 1,3,4-oxadiazole moieties were synthesized. The structures of these compounds were confirmed by spectroscopic data (IR, 1H- and 13C-NMR) and elemental analyses. Antifungal tests indicated that all the title compounds exhibited good antifungal activities against eight kinds of plant pathogenic fungi, and some showed superiority over the commercial fungicide hymexazol. Among them, compounds 5d, 5e, 5f, and 5i showed prominent activity against B. cinerea, with determined EC?? values of 5.21 μg/mL, 8.25 μg/mL, 8.03 μg/mL, and 21.00 μg/mL, respectively. The present work demonstrates that sulfone derivatives such as 5d containing a 1,3,4-oxadiazole moiety can be used as possible lead compounds for the development of potential agrochemicals.     

Design,synthesis and biological evaluation of 5-(2-(4-(substituted benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues as novel anti-tubercular agents

A series of thirty-six novel 5-(2-(4-(benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues were synthesized, characterized and screened for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. These compounds exhibited minimum inhibitory concentration between 1.56 and 50 μg/mL. Among these derivatives, compounds 10c, 10d, 10j, 10o and 10v (MIC 6.25 μg/mL) displayed moderate activity, while compounds 10e, 10l, 10q, 10w,10x, 12d, 12e and 12i (MIC 3.12 μg/mL) showed good anti-tubercular activity and compounds 10f, 10k, 10p, 10r, 12f, 12j and 12k (MIC 1.56 μg/mL) exhibited excellent anti-tubercular activity. In addition, MTT assay was accomplished on the active analogues of the series against mouse macrophage (RAW 264.7) cells to evaluate the cytotoxic effect of the newly synthesized compounds and selectivity index of the compounds was determined.     

Design,Synthesis, and Biological and In Silico Study of Fluorine‐Containing Quinoline Hybrid Thiosemicarbazide Analogues

A novel series of fluorine‐containing quinoline hybrid thiosemicarbazide analogues ( 8a–8l ) were synthesized and tested for their biological activities. The antibacterial results demonstrated that compounds 8d and 8l [minimal inhibitory concentration (MIC) 62.5 μg/mL] were shown to have higher biological activity than ampicillin against Escherichia coli. Compound 8b (MIC 25 μg/mL) was shown to have the highest activity than was ampicillin against Staphylococcus aureus. The antifungal results demonstrated that compound 8j (MIC 100 μg/mL) has shown good activity. Most of the targeted compounds have shown potent antimalarial activity. Compounds 8d (0.19 μg/mL), 8g (0.30 μg/mL), 8h (0.36 μg/mL), 8k (0.10 μg/mL), 8l (0.28 μg/mL), 8k (0.10 μg/mL), and 8l (0.28 μg/mL) have notable activity than does the reference drug quinine. Compounds 8d (0.27 μg/mL), 8g (0.30 μg/mL), and 8k (0.17 μg/mL) have shown excellent activity against chloroquine‐resistant strain. The MTT assay performed on peripheral blood lymphocyte cultures showed a high percentage of lymphocyte viability [ 8d (99.64), 8g (99.46), 8h (98.83), and 8k (99.51)] at a maximum dose (10 μg/mL), depicting no cytotoxicity of these compounds on human lymphocytes in vitro. A molecular docking study was performed on Pf‐DHFR‐TS inhibitor. A molecular dynamics study has shown compound 8g to have better affinity with protein. ADME‐Tox and pharmacophore study of synthesized compounds suggested prediction of active site.     

Synthesis and biological evaluation of glyco-GA compounds as anticancer agents

A series of novel glyco-gambogic acid（GA） compounds were synthesized and evaluated for their in vitro anti-proliferative activity against human hepatocellular carcinoma（HCC） cells.All compounds showed much better aqueous solubility（0.92- 1.89 mg/mL） than GA（0.013 mg/mL）,and displayed potent inhibition on HCC cells(IC₅₀:0.21-12.23μmol/L) and little affects on non-tumor liver cells(IC₅₀:42.56-86.43μmol/L),suggesting that glyco-GA compounds selectively inhibit HCC proliferation,and may be promising candidates for further intensive study.     

Determination of phenanthrene by antibody-coated competitive real-time immuno-PCR assay

A reliable selective and sensitive antibody-coated competitive real-time immuno-PCR (RT-IPCR) assay for the determination of phenanthrene (PH) was developed. Phenanthrene butanoic acid (γ-oxo-PHA) was synthesized as the hapten of PH. An active ester method was used to couple the PHA to bovine serum albumin to form an artificial immune antigen. Male New Zealand white rabbits were immunized with immune antigen to obtain polyclonal antibodies, with which a novel RT-IPCR assay for determination of PH was developed. Under the optimized assay conditions, PH can be determined in the concentration range from 10 fg/mL to 100 pg/mL with a detection limit of 5 fg/mL. The cross-reactivities of the anti-PH antibody to seven structurally related compounds were below 12.5%. Some environmental water samples were analyzed with satisfactory results, which showed good accuracy and suitability to analyze PH in environmental water. Compared with high-performance liquid chromatography, the recovery was lower or higher with agitation but would still be acceptable for use in an on-site field test to provide rapid, semiquantitative, and reliable test results for making environmental decisions.