Synthesis and antimicrobial activity of 8-alkylberberine derivatives with a long aliphatic chain

The compounds 8-ethyl- (2), 8-butyl- (3), 8-hexyl- (4), 8-octyl- (5), 8-decyl- (6) and 8-dodecylberberine chloride (7) were synthesized and tested for their antimicrobial activity in vitro to evaluate structure-activity relationships. Substitution of the alkyl groups at C-8 led to significant changes in the antimicrobial activity. All compounds were more potent against the tested microorganisms than berberine (1), especially against Gram-positive bacteria. The antimicrobial activity increased as the length of aliphatic chain was elongated and then decreased gradually when the alkyl chain exceeded eight carbon atoms. 8-octylberberine (5) displayed the highest antimicrobial activity of all compounds. The toxicity of compounds 2 - 7 was stronger than that of 1. However, upon elongating the aliphatic chain, the toxicity decreased gradually.     

Synthesis and antimicrobial activity of 3-alkoxyjatrorrhizine derivatives

The compounds 3-ethoxy- ( 2), 3-butoxy- ( 3), 3-hexyloxy- ( 4), 3-octyloxy- ( 5), 3-decyloxy- ( 6) and 3-dodecyloxyjatrorrhizine chlorides ( 7) were synthesized and tested for their antimicrobial activity in vitro to evaluate structure-activity relationships. Substitution of the H with alkyl groups at C-3-OH led to significant changes in the antimicrobial activity. The antimicrobial activity of the substituted derivatives was 32 - 1000 times higher than that of jatorrhizine ( 1), which increased as the aliphatic chain was elongated and then decreased slightly when the alkyl chain exceeded eight carbon atoms. 3-Octyloxyjatrorrhizine ( 5) displayed the highest antimicrobial activity of all compounds. The LD (50) values of compounds 1 - 7 were more than 6000 mg/kg body weight, showing a low toxicity. The toxicities of compounds 2 - 7 were slightly lower than that of ( 1).     

松属素及其衍生物的合成与抗菌活性

目的 合成松属素及其衍生物,研究其抗菌活性.方法 以2,4,6-三羟基苯乙酮为起始原料,经羟基保护、缩合、环化、脱保护合成目标化合物.用平皿二倍稀释法研究目标化合物的体外抗菌活性.结果共得到18个目标化合物,经1H-NMR、MS确证其结构.初步药理实验结果表明,多数化合物表现出较好的体外抗菌活性.结论松属素及其衍生物有可能成为新型结构的抗菌药物.     

Antimicrobial activity of oleanolic acid from Salvia officinalis and related compounds on vancomycin-resistant enterococci (VRE)

An extract from Salvia officinalis (Sage) leaves showed antimicrobial activity against vancomycin-resistant enterococci (VRE). We isolated the effective compound and identified it as oleanolic acid, a triterpenoid. We also tested antimicrobial activity of similar triterpenoids, ursolic acid, uvaol, betulinic acid and betulin. We found that ursolic acid also showed antimicrobial activity against VRE. The minimum inhibitory concentrations (MICs) of oleanolic acid and ursolic acid were 8 and 4 microg/ml, respectively. These two compounds also showed antimicrobial activity against Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). These compounds showed bactericidal activity against VRE at least for 48 h when added at concentrations that were two-times higher than their MICs.     

新型巯基蛋白酶抑制剂THTT衍生物的抗微生物活性

目的：研制针对各种耐药病原微生物的有效新药，合成一类新的含有四氢－2H－1，3，5－噻二嗪－2－硫酸环的化合物（Tetrahydro-2H-1,3,5-thiadiazine-2-thione,THTT)，并研究其抗微生物活性。方法：用5种G^ 菌和1种对10种新合成的化合物进行了生物活性实验。结果：大部分化合物对供试菌株均具有不同程度的抑制作用，对常见肠道菌如大肠杆菌，志贺菌对甲型副伤寒沙门菌，伤寒沙门菌的力活性较好；而对G^ 菌的金黄色葡萄球菌的力活性最强。其中化合物1，7，8，9，11，13抗菌活性较好。与阳性对照药物磺胺嘧啶钠注射液相比，10种化合物的抗菌活性均强于对照物。但是，铜绿假单胞菌对10种化合物均不敏感。结论：大部分化合物对所选常见致病菌有较好的抑菌活性，同时表明有较宽的抗菌谱，该类化合物值得进一步深入研究。     

Synthesis of novel 3-[5-ethyl-2-(2-phenoxy-ethyl)-pyridin]-5-substituted isoxazoline libraries via 1,3-dipolar cycloaddition and evaluation of antimicrobial activities

A series of novel 3-[5-ethyl-2-(2-phenoxy-ethyl)-pyridin]-5-substituted isoxazolines were synthesized via 1,3-dipolar cycloaddition of in situ generated nitrile oxide from 4-[2-(5-ethylpyridyl)-ethoxy]-benzaldoxime with alkenes to obtain new heterocyclic libraries containing a pyridine moiety in addition to the isoxazoline ring. The newly synthesized compounds were screened for their antimicrobial activity and were compared with standard drugs. The compounds demonstrated potent to weak antimicrobial activity. Of the compounds studied, compounds 3c and 3f showed significant antibacterial as well as antifungal activity. Compounds 3e and 3g showed moderate activity. The title compounds represent a novel class of potent antimicrobial agents.     

Synthesis and in vitro antimicrobial evaluation of condensed heterocyclic 6-substituted 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole and 1,3,4-oxadiazole derivatives of isoniazid

A series of 6-substituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole (3a-g) and 1,3,4-oxadiazole (4a-g, 5) derivatives of isoniazid were synthesized in satisfactory yield and pharmacologically evaluated for their in vitro antimicrobial activity. All the synthesized compounds were in good agreement with elemental and spectral data. A majority of the tested compounds showed good to moderate antimicrobial activity against all tested pathogenic bacterial and fungal strains.     

Synthesis of some 3- and 4-substituted 1,5-diphenylpyrrolidine-2,4-diones as potential antimicrobial and antineoplastic agents. Reactions with tetramic acid,Part 5

The condensation of 1,5-diphenylpyrrolidine-2,4-dione (1) with the carboxyl compounds 2a-f afforded the corresponding 3-arylidene-1,5-diphenylpyrrolidine-2,4-diones 3a-f. Reaction of the parent compound 1 with isatin (4) yielded the condensation product 5 in an acidic medium, whereas compound 6 was obtained in an alkaline medium. The condensation of the primary amines 7a-f with compound 1 afforded the corresponding 4-substituted amino-1,5-diphenyl-delta 3-pyrrolin-2-ones 8a-f. All the compounds synthesized were screened for their antimicrobial activity, and four compounds were selected for screening for their antineoplastic activity. The compounds tested showed both antimicrobial and antineoplastic activities.     

Antimicrobial activity of a new series of benzimidazole derivatives

Due to antimicrobial importance of benzimidazoles and hydrazones, some benzimidazolehydrazone compounds were synthesized to screen their antimicrobial activity. Structures of the synthesized compounds were elucidated by ¹H-NMR, IR and ES-MS spectral data and elemental analysis. The synthesized benzimidazole-hydrazones exhibited very weak antibacterial activity. However, antifungal activity of some of the synthesized compounds was very notable against Candida species. The compounds displaying important antifungal activity were screened for their toxicity. Artemia salina 96-well assay was used to determine cytotoxicity of the compounds. Tested compounds exhibited toxicity to different extents (LD₅₀ = 126.33−368.72 μg/mL). Nevertheless, determination of 3–14 folds higher LD₅₀ than minimum inhibitory concentration is a significant finding, which demonstrates that the compounds display antifungal activity at non-toxic concentration.     

Antimicrobial activity of 9-O-acyl- and 9-O-alkylberberrubine derivatives

For the structure-activity relationship study on berberrubine derivatives, a series of compounds bearing 9-O-acyl- and 9-O-alkyl-substituents were synthesized and tested for antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi. Octanoyl, decanoyl, lauroyl derivatives among the acyl analogs and hexyl, heptyl, octyl, nonyl, decyl, undecyl derivatives among the alkyl analogs showed strong antimicrobial activity against Gram-positive bacteria and fungi. As a whole, alkyl analogs were more active than acyl analogs for antimicrobial activity. Synthesized derivatives had no activity on Gram-negative bacteria. Too short or too long substituents decreased activity. These results suggest that the presence of lipophilic substituents with moderate sizes might be crucial for the optimal antimicrobial activity.     

水蚯蚓抑菌物质的分离与活性研究

目的从水蚯蚓中分离抑菌活性物质,并对其做活性研究。方法利用分部盐析和葡聚糖凝胶色谱等方法分离水蚯蚓组分,以大肠杆菌和金黄色葡萄球菌测试菌,通过琼脂糖扩散法和比浊法检测水蚯蚓组分的体外抑菌效果。结果水蚯蚓舍有抑菌活性物质,该物质对金黄色葡萄球菌的活性较强,对大肠杆菌的抑制作用较弱。结论水蚯蚓含有抑菌活性物质,这为进一步开发水蚯蚓资源提供了依据。     

Syntheses and bioactivities of 1-(hydroxyphenyl)-1-nonen-3-ones and related ethers and esters

A number of nuclear hydroxy styryl ketones and related compounds were prepared and evaluated for antineoplastic and antimicrobial activities as well as for analgesic, anti-inflammatory, and antianaphylactic properties. The second-order rate constants for the reaction of several esters with hydroxide ion in aqueous dioxane (50% v/v) at 36.9 degrees were determined. The screening results showed that activity against P-388 lymphocytic leukemia was found solely with the ethers and that antimicrobial properties were obtained virtually exclusively with the phenolic derivatives. All compounds showed analgesic properties, except for four that were algesic. While little anti-inflammatory activity was found, several compounds showed some antianaphylaxis.     

昆虫提取物的抗菌活性研究

相对于植物化学和海洋生物化学,昆虫次生代谢物的多样性可能是新药研究中一个更为珍稀的可替代资源。为寻找新的抗菌类化合物及开展昆虫天然产物化学的研究,本文对8种昆虫提取物进行了抗菌活性的筛选和评价。研究采用了圆形纸片扩散法,以相应抗生素作为阳性对照,对昆虫70%甲醇提取物进行抗菌活性测定。结果显示,除土鳖虫外,其余7中昆虫提取物均具有较强的抗革兰阳性菌或(和)革兰阴性菌的活性。并且文中使用的溶剂两段提取方法,为以后的昆虫次生代谢物的研究奠定了技术基础。该研究将为抗生素新药先导化合物的发现和拓展昆虫化学研究方向提供新的思路。     

Synthesis and biological evaluation of indole containing derivatives of thiosemicarbazide and their cyclic 1,2,4-triazole and 1,3,4-thiadiazole analogs

New indolic derivatives of thiosemicarbazides and some cyclic 1,2,4-triazol-5-thione analogs were synthesized. The newly synthesized compounds as well as some indole containing thiosemicarbazides, 1,2,4-triazoles and 1,3,4- thiadiazoles, which have been reported previously, were investigated for antimicrobial, antifungal and antiphage activity. Certain thiosemicarbazide derivatives and the corresponding cyclic 1,2,4-triazole analogs showed selective antimicrobial or antifungal activity, while they lack any antiphage activity. Antiphage activity was detected for one compound, bearing the 1,3,4-thiadiazole nucleus. The selectively active compounds cover a wide range of lipophilicity. Structure-activity relations show a remarkably similarity in the antimicrobial and antifungal behaviour of the thiosemicarbazides and their cyclic triazo-thien-5-yl analogs, while alpha-naphtyl substitution in the non indolic portion of the molecule is favorable. C5 substitution on the indolic nucleus may also be critical for selective activity.     

Evaluation of microalgae and cyanobacteria as potential sources of antimicrobial compounds

In recent decades, marine microorganisms have become known for their ability to produce a wide variety of secondary bioactive metabolites. Several compounds have been isolated from marine microorganisms for the development of novel bioactives for the food and pharmaceutical industries. In this study, a number of microalgae were evaluated for their antimicrobial activity against gram-positive and gram-negative bacteria, including food and plant pathogens, using various extraction techniques and antimicrobial assays. Disc diffusion and spot-on-lawn assays were conducted to confirm the antimicrobial activity. To measure the potency of the extracts, minimum inhibition concentrations (MIultCs) were measured. Three microalgae, namely Isochrysis galbana, Scenedesmus sp. NT8c, and Chlorella sp. FN1, showed strong inhibitory activity preferentially against gram-positive bacteria. These microalgal species were then selected for further purification and analysis, leading to compound identification. By using a mixture of different chromatography techniques gas chromatography–mass spectrometry (GC–MS) and high-performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS), we were able to separate and identify the dominant compounds that are responsible for the inhibitory activity. Additionally, nuclear magnetic resonance (NMR) was used to confirm the presence of these compounds. The dominant compounds that were identified and purified in the extracts are linoleic acid, oleic acid, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). These compounds are the potential candidates that inhibit the growth of gram-positive bacteria. This indicates the potential use of microalgae and their antimicrobial compounds as biocontrol agents against food and plant pathogens.     

Comparison of the antimicrobial and cytotoxic activities of twenty unsaturated sesquiterpene dialdehydes from plants and mushrooms.

Twenty unsaturated sesquiterpene dialdehydes were tested for antimicrobial, algaecidal, cytotoxic, and mutagenic activity. In addition to the known antifungal activity, polygodial (1) also exhibited antibacterial and cytotoxic activity; epipolygodial (2) was slightly less active. The most active compounds were: isovelleral (7), isoisovelleral (8), velleral (20), and methylmarasmate (6). With the exception of velleral (20), they also exhibited mutagenic activity in the Salmonella/microsome assay. Derivatization to less polar compounds usually increased the antimicrobial and cytotoxic effects and reduced mutagenicity, while the introduction of hydroxyl groups had the reverse effect.     

Synthesis and biological activities of cyclopropenone antibiotic penitricin and congeners.

A number of derivatives of the cyclopropenone antibiotic penitricin have been synthesized by the reaction of metalated cyclopropenone acetals with electrophiles. Studies on the antimicrobial structure-activity relationships indicated that the penitricin skeleton, hydroxymethylcyclopropenone, is indispensable for antimicrobial activity. These compounds were also found to display cytotoxic activity.     

Synthesis, anti-inflammatory and antimicrobial activities of new 1,2,4-oxadiazoles peptidomimetics

A new series of 1,2,4-oxadizoles 6a-g have been synthesised in good yields using the peptide synthesis strategy. The prepared compounds were tested for anti-inflammatory and antimicrobial activities. The anti-inflammatory activities were determined in the rat paw oedema induced by carrageenin. Compounds 6a, c, f and g (i.v.) significantly inhibited the rat paw oedema induced by carrageenin depending upon the dose employed. The compounds were also evaluated for their in vitro antimicrobial activity. Some compounds were found to have significant activity against Gram positive and Gram negative microorganisms.     

Synthesis and antimicrobial evaluation of some arylhydrazones of 4-[(2-methylimidazo[1,2-a]pyridine-3-yl)azo]benzoic acid hydrazide

A short series of arylhydrazones of 4-[(2-methylimidazo[1,2-a]pyridine-3-yl)azo]benzoic acid hydrazide was synthesized and tested for antimicrobial activity. All of the compounds show antimicrobial activity against Escherichia coli. A few members were also active against Klebsiella pneumoniae, Staphylococcus aureus and Pseudomonas aeruginosa. The interplanar angle (theta) between the aryl ring and the adjacent azomethine group of some representative compounds was measured by electronic absorption spectroscopy. No structure-activity-relationship between interplanar angle or lipophily and activity was found.