新型含氮五元杂环E-β-法尼烯类似物的合成及生物活性研究

为了寻求新型蚜虫防治先导化合物, 以蚜虫报警信息素的主要成分E-β-法尼烯(E-β-farnesene, 简称EBF)的骨架结构为母体, 分别用N-氰基-亚胺基-1,3-噻唑烷、2-噻唑硫酮、2-羰基-1,3-噁唑烷、1-取代-2-硝基亚胺基-1,3-咪唑烷等含氮五元杂环取代EBF中的共轭双键, 设计合成了8个未见文献报道的EBF类似物, 其结构均经¹H NMR, IR和元素分析确证, 并分析比较了不同类型杂环的化学反应和生物活性差异. 初步生物活性试验结果表明, 目标化合物对蚜虫具有一定的生物活性, 其中4e在5个测试浓度下的活性均优于对照药剂; 有意思的现象是, 一些在高浓度(1000 μg/mL)下活性低于对照药剂噻虫啉的目标物(如 4a～4c, 4f～4h), 在低浓度(如62.5 μg/mL)下对蚜虫的生物活性反而高于对照药剂.     

取代苯丙酮肟衍生物的合成、QSAR研究以及优化

本文介绍了用结合化学、生物实验以及计算机辅助分子设计方法优化对瓜类白粉病毒有抑制作用的先导化合物的研究。用3－取代氨基－1－芳基丙酮－1－肟以及卤代烃合成了44个取代苯丙酮肟衍生物。生物测试的结果表示这些化合物大部分对瓜类白粉病毒有抑制作用。基于这些生物测试,对这44个化合物做了QSAR研究。根据所得CoMFA (rcv2, S 以及 r2 分别为0.577, 0.258, 0.962) 和 CoMSIA (rcv2, S 以及 r2 分别为0.583, 0.343, 0.932) 模型,设计了3个新化合物,而且预测结果显示,它们无致癌和致突变毒性。测试结果显示预测活性与实验活性相对应,说明这两个模型具有较高的预测准确率。     

N′-(取代嘧啶-2-基)-N-菊酰硫脲的合成与生物活性研究

采用活性基团拼接法, 将第一菊酸构型中的最高活性组分(＋)-反式菊酸以及二氯菊酸引入到含取代嘧啶环的酰基硫脲结构中, 合成了5个未见文献报道的N′-(取代嘧啶-2-基)-N-(＋)-反式菊酰硫脲衍生物(3a～3e)和3个均未见文献报道的N′-(取代嘧啶-2-基)-N-二氯菊酰硫脲(3f～3h), 结构经元素分析、IR和¹H NMR得到确证. 初步的生物活性测试结果表明: 大部分化合物具有较好的杀菌活性, 有的化合物兼具除草和杀菌活性, 有的化合物兼具杀虫和杀菌活性.     

Theoretical Investigations of the Effect of a Homologous Series of Anionic Surfactants on the Metabolism Bioactivity of Chromobacterium violaceum

Theoretical calculations were performed to obtain physicochemical properties associated with the effect of homologous anionic n-alkylsulfate surfactants on the metabolism of Chromobacterium violaceum. The quantitative experimental effects on the respiration process were those obtained from calorimetric data and were used to correlate the Structure–Activity–Relationship (SAR) of these compounds. Semiempirical AM1 and ab initio DFT levels, employing the set CEP-31G, were used for the theoretical calculations and were parameterized using the continuum-solvation model COSMO for solvent contributions. Chemometric analyses (HCA: hierarchical cluster analysis and PCA: principal component analysis) were used to correlate the physicochemical properties of these compounds and their biological activities. The results indicate that the biological activities of these compounds increase as the hydrocarbon chain length, volume, molar volume and exothermic enthalpy of formation (Δ_f H ^∘) increase; in contrast they decrease with decreases of the solvent effect (SE), ionization enthalpy (IE) and HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energies.     

Terephthalaldehyde: An Effecient Key Precursor for Novel Synthesis of Some Interesting Bis‐thiazoles and Bis‐triazolopyrimidinones

Novel bis‐thiazoles were synthesized in high and efficient yields from the reaction of thiosemicarbazones with halogenated compounds. Also, new bis‐triazolopyrimidines were prepared from the reaction of hydrazonoyl chlorides with bis‐thione derivative. All prepared compounds were fully characterized by spectral methods. The synthesized bis‐compounds will be attractive species for the medicinal researchers to investigate their biological activity.     

Synthesis and antimicrobial activity of a series of optically active quaternary ammonium salts derived from phenylalanine

We synthesized nine quaternary ammonium compounds (QUATs) starting from phenylalanine, N-alkyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromides, which were prepared as optically pure substances. Five compounds were prepared as S-enantiomers and four compounds as R-enantiomers. These compounds were evaluated by their activities against bacteria and fungi. Three microbial strains were used in the study: the gram-negative bacteria Escherichia coli, the gram-positive bacteria Staphylococcus aureus and the fungi Candida albicans. The activities were expressed as minimum bactericidal or fungicidal concentrations (MBC). The most active compounds were (2S)-N-tetradecyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromide and (2R)-N-tetradecyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromide, with MBC values exceeding those of commercial benzalkoniumbromide (BAB) used as standard. The relationships between structure and biological activity of the tested QUATs were quantified by the bilinear model (QSAR) and are discussed.     

Design,Synthesis and Biological Activities of Novel Benzoyl Hydrazines Containing Pyrazole

In search of environmentally benign compounds with high biological activity, low toxicity and low resistance, 8 novel benzoyl hydrazines containing pyrazole were designed and synthesized. All compounds were characterized by ¹H NMR spectra and HRMS. The preliminary results of biological activity assessment indicated that most of title compounds exhibited certain insecticidal activities against Mythimna separata Walker at 200 mg·L^?1 but excellent fungicidal activities against six fungus at 50 mg·L^?1, which were better than the control.     

Synthesis,Antimicrobial, and Brine Shrimps Lethality Assays of 3,3‐Diaryl‐4‐(1‐methyl‐1H‐indol‐3‐yl)azetidin‐2‐ones

The paper describes the synthesis, characterization data, and biological activity (antibacterial, antifungal, and brine shrimps lethality) of new azetidin‐2‐ones. The compounds have been synthesized by the reaction of diarylketenes, generated in situ from thermal decomposition of the 2‐diazo‐1,2‐diarylethanones, with N‐(1‐methyl‐1H‐indol‐3‐yl)methyleneamines. The compounds have been characterized by elemental analysis and spectral (IR, ¹H and ¹³C NMR, and MS) data. The paper also reports the results of antibacterial, antifungal, and brine shrimps lethality assays of these compounds. Some of the compounds exhibited significant biological activity.     

Synthesis and Insecticidal Activities of Novel Phthalic Acid Diamides

In order to discover novel insecticides with the new action mode on ryanodine receptor (RyR), a series of novel phthalic acid diamide derivatives were designed and synthesized. All compounds were characterized by ¹H NMR spectra and HRMS. The preliminary results of biological activity assessment indicated that some title compounds exhibited excellent insecticidal activities against Mythimna separata, Spodoptera exigua, and Plutella xylostella. The title compound 3‐nitro‐N‐cyclopropyl‐N′‐[2‐methyl‐4‐(perfluoropropan‐2‐yl)phenyl]phthalamide ( 4a ) was more efficient against diamondback moths than the control (chlorantraniliprole). The effects of some title compounds on intracellular calcium of neurons from the Spodoptera exigua proved that the title compounds were RyR activators.     

Antioxidant and DNA damage protecting activities of newly synthesized thiol bridged bis-benzimidazole derivative and its dicationic analogue

Two new types of bis-benzimidazole derivatives containing thiol group have been prepared and characterized. The compounds contain sulfur with imidazole ring show promising biological activities such as antioxidant, anticancer, antimicrobial and etc. The aim of this study was synthesis of benzimidazole derivatives which not only show antioxidant activity but also protect DNA from oxidative damage. Antioxidant activities of the synthesized compounds were investigated with DPPH and hydrogen peroxide radical scavenging assays. DNA nicking assay was applied to establish activity of compounds to protect plasmid DNA from Fenton's reagent radicals. Both compounds had antioxidant activity, however, activity of dicationic analogue was greater than well-known antioxidant Vit C. IC₅₀ values calculated according to DPPH method were 14.5 μM for dicationic analogue ( 2 ) and 57.5 μM for 1,2-bis(1-methyl-1H-benzo[d]imidazol-2-ylthio)ethane ( 1 ). In hydrogen peroxide scavenge assay IC₅₀ values of compounds were 638.6 μg/mL for 1,2-bis(1-methyl-1H-benzo[d]imidazol-2-ylthio)ethane ( 1 ), 398.9 μg/mL for dicationic analogue ( 2 ). Furthermore, dicationic analogue promised an effective DNA protection due to its positive charge interacting with negatively charged DNA. Also the high solubility of the dicationic analogue in water due to its positive charge could provide a great advantage in biological applications.     

New class of diethyl substituted phosphoramidimidates and phosphonimidates: synthesis,spectral characterization and antimicrobial activity

Abstract

A series of new class of diethyl N-2-hydroxyethyl-N'-substituted phosphoramidimidates 6(a–e) and diethyl P-morpholino-N-substituted phosphonimidates 6(f–j) was synthesized. The precursor intermediates, diethyl substituted phosphoramidites 3(a–b) were prepared initially by a reaction of various amines 1(a–b) and diethyl phosphorochloridite (2) and then they were treated by in situ with aromatic/alkyl azides through Staudinger reaction to accomplish title products. Structures of all the synthesized compounds were characterized by spectroscopic data such as IR, NMR (¹H, 13C, ³¹P), mass, and elemental analyses. The synthesized compounds were screened for their in vitro antimicrobial activity to understand their biological potency. The biological screening results disclosed that compounds 6b, 6c, 6e, 6g, 6h and 6j having potent antimicrobial activity against all the tested pathogens.     

Unprecedented Quassinoids with Promising Biological Activity from Harrisonia perforata

Perforalactone A ( 1 ), a new 20S quassinoid with a unique cagelike 2,4‐dioxaadamantane ring system and a migrated side chain, was isolated from the plant Harrisonia perforata together with two biosynthetically related new quassinoids. The structures of these natural products were elucidated by NMR spectroscopy, X‐ray diffraction analysis, computational modeling, and the CD excitation chirality method. The compounds exhibited notable biological properties, including insecticidal activity against Aphis medicaginis Koch and antagonist activity at the nicotinic acetylcholine receptor of Drosophila melanogaster. The structural features of these compounds may be related to their promising biological characteristics. Their biosynthesis and an alternative origin of quassinoid‐type natural products are also discussed.     

Synthesis and Antimicrobial and Antioxidant Activities of Sulfonamide Derivatives Containing Tetrazole and Oxadiazole Rings

In the present work, we synthesized new sulfonamide derivatives with 1,3,4‐oxadiazole moiety and tetrazole ring. The synthesized derivatives of sulfonamides were characterized through Fourier transform infrared, ¹³C‐APT‐NMR, ¹H‐NMR, and high‐resolution liquid chromatography–mass spectrometry. The biological activities of resulting compound were also investigated and observed that the compounds reveal strong antimicrobial activity over some important bacterial strains including Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, and Staphylococcus aureus ATCC 29213. The in vitro antifungal properties of synthesized compounds were also a target using Candida albicans NRRL Y‐477 and Saccharomyces cerevisiae fungal strains. We have provided a useful guideline for future studies about the effect of the chemical structures of sulfonamide compounds on the biological activities. Among the target compounds, 7b , 7c , 7d , and 7e demonstrated surprisingly high antimicrobial activities than did others.     

Synthesis and Structure-Activity Relationships of Juvenoids Derived from 2-(4-hydroxybenzyl)cycloalkan-1-ones

Juvenoids 16–30, 32, 36, 38–41, 44–46 , and 49–56 containing carbamate, carbonate, and urea moieties in the molecule were synthesized and subjected to a biological screening (Schemes 2–7, Table 2). Carbamate juvenoids 1–4 were used as reference compounds for a detailed structure-activity study of their analogues. A clear relationship between the nature of the side chain functional group and the biological activity was found. Surprisingly, not only the juvenoids 1–4 but also 38–41 , the compounds with a reversed carbamate N,O-substitution pattern, showed very promising biological activity. In contrast, the carbonate and urea derivatives displayed a remarkably low activity. The relationship between the size and substitution at atoms C(2) and C(3) of the saturated ring and the biological activity is very complex and is still not completely understood.     

Synthesis and Blood Glucose Lowering Activity of Novel Benzenesulfonyl-Urea Derivatives

Treatment of the pyridazinone derivatives ( 1a, 1b ) with ethyl chloroformate afforded novel carbamates ( 2a, 2b ). Subsequent treatment of 2a, 2b with appropriate amines gave novel benzenesulfonylurea derivatives ( 3a–i ). All these compounds were characterized on the basis of ¹ H NMR, IR, Mass spectral data and elemental analysis results. Preliminary biological testing of urea derivatives revealed that some compounds possess significant blood sugar lowering activity. Four compounds ( 3c, 3f, 3g , and 3h ) were found to have promising blood glucose lowering activity and may be used as lead compounds for developing new antidiabetic drugs.     

含二茂铁的β-内酰胺的研究进展

β-内酰胺类抗生素是目前最具应用价值的抗生素, 其结构特征具有β-内酰胺环的基元结构, 该类化合物的设计、合成和立体化学研究一直是有机合成化学研究的前沿和热点领域. 二茂铁凭借其独特的结构和多样的性质, 在生物和医药方面均有广泛的应用价值. 因此, 二茂铁修饰的β-内酰胺是一类结构新颖且具有潜在生物活性的化合物. 对该类化合物的深入研究, 将对新型抗生素的研发提供重要的指导意义. 综述了近年来青霉烷类和头孢烯类β-内酰胺及单环类β-内酰胺这两大类含二茂铁取代的β-内酰胺衍生物的合成与生物活性的研究进展.     

Synthesis and Antimicrobial Activity of New Thiazolidine‐Based Heterocycles as Rhodanine Analogues

A new series of compounds containing thiazole nucleus as Rhodanine analogues have been synthesized. The new compounds were prepared from the reactions of the thiosemicarbazones ( 3a,b ) with a series of α‐halo carbonyl compounds to give the corresponding Rhodanine analogues. The thiosemicarbazones derivatives ( 3a,b ) were reacted also with hydrazonoyl chlorides to afford the corresponding tri‐substituted and tetra‐substituted thiazoles. The structures of the newly synthesized compounds were confirmed by elemental analysis and spectral data. The biological activities of the new synthesized Rhodanine analogues' were evaluated for their antimicrobial activities. The results showed that some of these compounds showed excellent activity against two fungal strains, including Aspergillus niger and Aspergillus flavus, in addition to three yeast strains, including Saccharomyces cervesi, Candida albicans NRRL Y‐477, and Candida Pathological specimen compared with the ketoconazol, as the reference drug.     

Derivational,Structural, and Biological Studies of Some New Pyrazolyl,Isoxazolyl, Pyrimidinyl,Pyridazinyl, and Pyridopyridazinyl from 4‐Substituted Antipyrine

(1,5‐Dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)carbono‐hydrazonoyl dicyanide was used as a key intermediate for the synthesis of novel pyrazole, isoxazole, pyrimidine, and pyridazine derivatives. The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹H‐NMR, ¹³C‐NMR, and mass spectra). The compounds were tested for their in vitro antibacterial activity against Gram‐positive bacteria as (Staphylococcus aureus and Bacillus subtilis ) and Gram‐negative bacteria (Pseudomonas aeruginosa and Escherichia coli ). The investigated compounds were tested against two strains of fungi Botrytis fabae and Fusarium oxysporum using diffusion agar technique. The biological results showed clearly that most of the synthesized compounds revealed mild to moderate activity against the used microorganisms.