Acetophenones with selective antimycobacterial activity

AIMS: Mycobacteria are a serious cause of infections in humans, with limited treatment options, as no new antibiotics have been developed against mycobacteria since the 1960s. In this study, the antimycobacterial activity of a small library of acetophenone (AP) compounds was analysed. METHODS AND RESULTS: Twenty-three AP derivatives were examined for activity against mycobacteria using a microbroth assay. The compounds were bacteriostatic, with the most effective (cyclohexylacetophenone and piperidinoacetophenone) having minimal inhibitory concentrations of 246 microM. Active compounds tended to be more hydrophobic, and may work by alkylation of as yet undetermined intracellular target protein(s). Cytotoxicity against eukaryotic cells was also determined and appears to be unrelated to the bacteriostatic activity. SIGNIFICANCE AND IMPACT OF THE STUDY: AP may serve as a novel group of useful therapeutics against the mycobacteria.     

Structure‐Activity Relationships and Potent Cytotoxic Activities of Terphenyllin Derivatives from a Small Compound Library

A small library of 120 compounds was established with seventy new alkylated derivatives of the natural product terphenyllin, together with 45 previous reported derivatives and four natural p‐terphenyl analogs. The 70 new derivatives were semi‐synthesized and evaluated for cytotoxic activities against four cancer cell lines. Interestingly, 2′,4′′‐diethoxyterphenyllin, 2′,4,4′′‐triisopropoxyterphenyllin, and 2′,4′′‐bis(cyclopentyloxy)terphenyllin showed potent activities with IC₅₀ values in a range from 0.13 to 5.51 μM, which were similar to those of the positive control, adriamycin. The preliminary structure–activity relationships indicated that the introduction of alkyl substituents including ethyl, allyl, propargyl, isopropyl, bromopropyl, isopentenyl, cyclopropylmethyl, and cyclopentylmethyl are important for improving the cytotoxicity.     

氨基糖苷-(3)-乙酰转移酶II的表达纯化及初步活性

用PCR扩增的氨基糖苷-(3)-乙酰转移酶II[aac(3)-II]基因构建了能表达较高活性AAC(3)-II的重组工程菌,并获取重组AAC(3)-II。含pET28a质粒的工程菌转入aac(3)-II基因前后对氨基糖苷类抗生素的最低抑菌浓度进行比较,重组菌超声裂解上清液及其纯化的AAC(3)-II进行SDS-PAGE和Western印迹电泳鉴定。最低抑菌浓度表明转入aac(3)-II基因的工程菌比未转入的工程菌对庆大霉素(gentamicin,GEN)的提高了256倍,对妥布霉素(tobramycin,TOB)及其奈替米星(netilmicin,NTL)提高了16倍,电泳鉴定表明纯化获取的是重组AAC(3)-II,其相对分子质量约为32kDa,纯度大于95%,纯化后的10μgAAC(3)-II,分别在10s内使80μgGEN、30s内使80μgTOB和NTL乙酰化而失去抑菌作用。研究为氨基糖苷类抗生素伴侣的开发研究初步打下基础。     

Antimelanogenic Activity of Ocotillol‐Type Saponins from Panax vietnamensis

The ocotillol (OCT)‐type saponins have been known as a tetracyclic triterpenoid, possessing five‐ or six‐membered epoxy ring in the side chain. Interestingly, this type saponin was mostly found in Panax vietnamensis Ha et Grushv ., Araliaceae (VG), hence making VG unique from the other Panax spp. Five OCT‐type saponins, majonoside R2, vina‐ginsenoside R2, majonoside R1, pseudoginsenoside RT4, vina‐ginsenoside R11, together with three protopanaxadiol (PPD)‐type saponins and four protopanaxatriol (PPT)‐type saponins from VG were evaluated for their antimelanogenic activity. All of isolates were found to be active. More importantly, the five OCT‐type saponins inhibited melanin production in B16‐F10 mouse melanoma cells, without showing any cytotoxicity. Besides ginsenoside Rd and ginsenoside Rg3 in PPD and notoginsenoside R1 in PPT‐type saponins, majonoside R2 was the most potent melanogenesis inhibitory activity in OCT‐type saponins. In this article, we highlighted antimelanogenic activity of OCT‐type saponins and potential structure–activity relationship (SAR) of ginsenosides. Our results suggested that OCT‐type saponins could be used as a depigmentation agent.     

Benzylidine indane-1,3-diones: As novel urease inhibitors; synthesis,in vitro,and in silico studies

Current study deals with the evaluation of indane-1,3-dione based compounds as new class of urease inhibitors. For that purpose, benzylidine indane-1,3-diones (1–30) were synthesized and fully characterized by different spectroscopic techniques including EI-MS, HREI-MS, ¹H, and ¹³C NMR. All synthetic molecules 1–30 were evaluated for urease inhibitory activity and showed good to moderate inhibitory potential within the range of (IC₅₀ = 11.60 ± 0.3–257.05 ± 0.7 µM) as compared to the standard acetohydroxamic acid (IC₅₀ = 27.0 ± 0.5 µM). Compound 1 (IC₅₀ = 11.60 ± 0.3 µM) was found to be most potent inhibitor amongst all derivatives. The key binding interactions of most active compounds within the enzyme pocket were evaluated through in silico studies.     

新疆部分特色林果果壳的抗菌活性研究

目的:研究新疆特色林果核桃、巴达木果壳乙醇提取物的抑菌特性。方法:用滤纸片法检验果壳乙醇提取物对金黄色葡萄球菌、枯草芽孢杆菌、大肠杆菌和变形杆菌的抑菌活性,通过液体培养基稀释法测定最低抑菌浓度。结果:巴达木乙醇提取物(25%乙醇提取10 h)对大肠杆菌有较好的抑菌效果,最低抑菌浓度(MIC)为25%;核桃乙醇提取物(25%乙醇提取24 h)对大肠杆菌有较好的抑菌效果,MIC为6.25%。结论:核桃、巴达木果壳乙醇提取物对受试菌具有较好的抑菌效果,为进行大规模开发利用提供了有效依据。     

Antifungal activity of essential oils and their combinations in in vitro and in vivo conditions

Natural additives are in demand for the control of microbial growth in foods. Several natural compounds including essential oils (EOs) are being explored for food uses. In the present investigation, the antifungal activity of cinnamaldehyde, eugenol, peppermint and clove EOs and their combinations was evaluated against 12 species of Aspergillus, Fusarium, Penicillium and Rhizopus in in vitro and tomato fruit system (in-vivo). The EOs were able to inhibit complete growth of tested fungi at or below 0.6% level and 80?μL of EOs (except peppermint oil) in in vitro condition and tomato system, respectively. The fractional inhibitory studies showed either additive or indifferent effect by combining eugenol and peppermint, and indifferent or antagonist effect by combining the cinnamaldehyde and clove in both in vitro and in vivo studies. The findings may be useful for application of these EOs in foods, but their effects on organoleptic quality of foods need to be investigated.     

Activity of natural antimicrobial compounds against Escherichia coli and Salmonella enterica serovar Typhimurium

AIMS: The objective of this study was to evaluate the inhibitory activity of several natural organic compounds alone or in combination with nisin against Escherichia coli and Salmonella Typhimurium. METHODS AND RESULTS: The minimum inhibitory concentration (MIC) of five natural organic compounds were determined, and the effect of their combinations with nisin was evaluated by the checkerboard assay using the Bioscreen C. As expected, nisin by itself showed no inhibition against either of the Gram-negative bacteria. Thymol was found to be the most effective with the lowest MIC values of 1.0 and 1.2 mmol 1-1 against Salm. Typhimurium and E. coli, respectively. After thymol, the antimicrobial order of the natural organic compounds was carvacrol > eugenol > cinnamic acid > diacetyl. However, the combination of nisin with the natural organic compounds did not result in the enhancement of their antimicrobial activities. On the contrary, combination of nisin with diacetyl against Salm. Typhimurium resulted in an antagonism of diacetyl activity. CONCLUSIONS: While the individual natural organic compounds showed inhibitory activity against the two Gram-negatives, their combinations with nisin showed no improvement of antimicrobial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows the potential of the natural organic compounds to control E. coli and Salm. Typhimurium.     

Design,Synthesis, and Cytotoxic Activities of Indole and Indazole-Based Stilbenes

To develop new highly effective anticancer agents derived from naturally occurring stilbene scaffold, in total of 24 indole and indazole-based stilbenes including 17 new compounds were designed according to molecular hybridization strategy and synthesized via Witting reaction. The cytotoxic screening results against human tumor cell lines (K562 cells and MDA-MB-231 cells) showed that indole and indazole-based stilbenes are of great interest for developing anticancer agents as eight derivatives possessed strong antiproliferative activities with IC₅₀ values less than 10 μM, and those synthetic derivatives displayed more higher cytotoxicities against K562 cells than MDA-MB-231 cells. In particular, indole-based stilbene bearing piperidine exhibited the most potent cytotoxicities against both K562 and MDA-MB-231 cells with IC₅₀ values 2.4 μM and 2.18 μM, respectively, along with a remarkable selectivity towards human normal L-02 cells. Together, the results suggested that indole and indazole-based stilbenes are promising anticancer scaffolds worthy of further investigation.     

棘白菌素对氟康唑耐药的念珠菌体外药物敏感性的研究

目的评价3种棘白菌素类药物（卡泊芬净、米卡芬净、阿尼多芬净）体外对氟康唑耐药念珠菌的药物敏感性。方法采用微量液体稀释法和琼脂稀释法测定最小抑制浓度（MIC）。结果微量液体稀释法：59株耐药白念珠菌3种药物MIC50均为0.06μg/mL,米卡芬净、阿尼多芬净的MIC范围均为0.015～0.125μg/mL,卡泊芬净为0.015～0.25μg/mL;8株耐药光滑念珠菌MIC值均为0.063μg/mL。琼脂稀释法：59株耐药白念珠菌和8株耐药光滑念珠菌3种药物MIC值均为0.063μg/mL。结论3种棘白菌素类药物可能具有治疗氟康唑耐药的念珠菌感染的临床价值。     

链霉菌H03发酵液提取物的抗菌活性研究

以常见的病原细菌和植物病原真菌为指示菌研究了链霉菌发酵液提取物的抗菌活性,测定了发酵液提取物的抗菌谱和最小抑菌浓度(MIC)。结果表明:与青霉素、链霉素相比,该菌发酵液提取物的抗菌范围更广,对植物病原真菌棉花黄萎病菌、苹果轮纹病菌、小麦赤霉病菌、油菜菌核病菌、黄瓜炭疽病菌、甜菜褐斑病菌、稻瘟病菌,以及常见病原细菌大肠杆菌、枯草杆菌、绿脓杆菌和金黄色葡萄球菌都具有明显的抑制作用。利用试管二倍稀释法测定发酵液提取物对上述诸菌的最小抑菌浓度(MIC),结果分别为0.125、0.062 5、0.125、0.25、0.015、0.03、0.015、0.015、0.03、0.250、.015 mg/mL。其中对植物病原真菌中的黄瓜炭疽病菌、甜菜褐斑病菌、稻瘟病菌,以及病原细菌中的大肠杆菌、枯草杆菌、金黄色葡萄球菌抑制效果最佳。将发酵液提取物置于100℃下加热处理10 min后,其对金黄色葡萄球菌的抑菌活性不变,说明该发酵液提取物具有较好的热稳定性。     

Template synthesis of macrocyclic complexes and their spectroscopic and antibacterial studies

A new series of macrocyclic complexes of type [M(TML)X]X₂, where M = Cr(III), Fe(III), TML is tetradentate macrocyclic ligand, and X = Cl^?, NO₃^?, CH₃COO^?, have been synthesized by condensation of isatin and ethylenediamine in the presence of metal salt. The complexes were synthesized by both conventional and microwave methods. The complexes have been characterized with the help of elemental analysis, conductance measurement, magnetic measurement, and infrared, far infrared, and electronic spectral studies. Molar conductance values indicate them to be 1:2 electrolytes. Electronic spectra along with magnetic moments suggest five-coordinate square pyramidal geometry for these complexes. The complexes were also tested for their in vitro antibacterial activity. Some of the complexes showed satisfactory antibacterial activitiy.     

螺卷毛壳霉代谢产物的抗菌活性研究(英文)

采用管碟法首次对螺卷毛壳霉（Chaetomium cochloides）的含硫次生代谢产物（1—5）进行了体外抗细菌和抗真菌活性测定,并对其构效关系进行了研究。活性测定显示化合物1—5对革兰氏阳性细菌（Staphylococcus aureus）具有较强的抑制活性,其中化合物1的抑菌活性最强。构效关系研究表明位于C-3’和C-6’之间的二硫桥为化合物的抑菌活性中心,C-3与C-11a之间的二硫桥和N-6与O—3’之间的大环结构能够增强活性。     

Synthesis and Antiproliferative Activity of New Thiosemicarboxamide Derivatives

To discover new anticancer agents, two series of thiosemicarboxamide derivatives were synthesized and evaluated for their antiproliferative activity against human cancer cells in vitro. Most target compounds (especially 3f , 3g , and 3h ) exhibit potent antiproliferative activity against HeLa cells. Importantly, compound 3h , bearing a 4-methylphenyl substituent at N position of thiourea moiety, has significant and broad-spectrum inhibitory activities against cancer cells (HepG2, HeLa, MDA-MB231, A875, and H460 cells) with low IC₅₀ values (<5.0 μM) and shows low toxicity to normal LO2 and MRC-5 cells. Further studies show that compound 3h exerts high inhibitory activity in cancer cells by inducing the G2/M-phase arrest of cancer cells. Collectively, this study presents compound 3h as a new entity for the development of cell cycle arrest inducers for the treatment of cancer.     

Evaluation of Antibacterial Activity of Lavandulapedunculata subsp. atlantica (Braun‐Blanq.) Romo Essential Oil and Selected Terpenoids against Resistant Bacteria Strains–Structure–Activity Relationships

The genus Lavandula is known for its different uses in traditional medicine. This study is interested in the chemical composition of Lavandulapedunculata subsp.atlantica (Braun‐Blanq. ) Romo as well as evaluating its antibacterial potential against multi‐resistant strains. The analysis of Lavandulaatlantica essential oil (LAEO) allows the identification of 47 components representing 93.6 % of all identified. The main constituent of LAEO was camphor (50.4 %), followed by fenchone (14.1 %) and camphene (5.6 %). The antibacterial assays revealed that LAEO was active against all the studied bacteria. A preliminary study of the relationship between certain terpenoids and antibacterial activity was also carried out in order to note the compound(s) that are responsible for LAEO's antibacterial activity. This study showed that the activity of the essential oil may be due to the presence of certain minor compounds such as carvone, considering the presence of the synergistic effect between the essential oil.     

新型氟喹诺酮衍生物对水产致病菌及其生物被膜的抑制作用研究北大核心

【目的】细菌的耐药性给动物抗感染和疾病治疗带来了极大的困难和挑战,生物被膜是导致细菌耐药性的主要原因之一,本研究检测分析了氯丙酰基克林沙星对7株菌株的抗菌活性及其生物被膜形成能力,以期发现氯丙酰基克林沙星是否具有抗菌活性。【方法】本研究通过打孔法和微量肉汤二倍稀释法进行常规药敏试验以测定最小抑菌浓度(minimum inhibitory concentration,MIC)和最小杀菌浓度(minimum bactericidal concentration,MBC),通过结晶紫染色法检测这7株受试菌在药物亚抑菌浓度下的生物被膜形成能力以及生长速率来测定氯丙酰基克林沙星的抑菌能力。【结果】实验结果显示,氟喹诺酮类衍生物氯丙酰基克林沙星药物对4株受试革兰氏阴性菌的MIC≤10 mg/L、MBC≤48 mg/L,对3株受试革兰氏阳性菌也呈现敏感状态(MIC≤10 mg/L,MBC≤10 mg/L)。结晶紫染色法检测发现,这7株受试菌在药物亚抑菌浓度下的生物被膜形成能力以及生长速率显著下降,说明氯丙酰基克林沙星在亚抑菌浓度即具有良好的抑菌活性。【结论】本研究证明氯丙酰基克林沙星可用作抗菌剂,并为新型生物被膜抗菌剂或细菌感染治疗药物的开发提供了新的依据。     

Antimicrobial activity of honey from the stingless bee Trigona carbonaria determined by agar diffusion,agar dilution,broth microdilution and time‐kill methodology

Aims: The aim of this study was to determine the spectrum of antimicrobial activity of 11 samples of stingless bee honey compared to medicinal, table and artificial honeys. Methods and Results: Activity was assessed by agar diffusion, agar dilution, broth microdilution and time‐kill viability assays. By agar dilution, minimum inhibitory concentration (MIC) ranges were 4% to >10% (w/v) for Gram‐positive bacteria, 6% to >16% (w/v) for Gram‐negative bacteria and 6% to >10% (w/v) for Candida spp. By broth microdilution, all organisms with the exception of Candida albicans and Candida glabrata were inhibited at ≤32% (w/v). Geometric MIC (w/v) means for stingless bee honeys ranged from 7·1% to 16·0% and were 11·7% for medicinal honey and 26·5% for table honey. Treatment of organisms with 20% (w/v) stingless bee honey for 60 min resulted in decreases of 1–3 log for Staphylococcus aureus, >3 log for Pseudomonas aeruginosa and <1 log for C. albicans. Similar treatment with each control honey resulted in decreases of <1 log for all organisms. Conclusions: Stingless bee honey has broad‐spectrum antibacterial activity although activity against Candida was limited. Stingless bee honey samples varied in activity and the basis for this remains to be determined. Significance and Impact of the Study: Stingless bee honey had similar activity to medicinal honey and may therefore have a role as a medicinal agent.     

Benzothiazole analogs as potential anti-TB agents: computational input and molecular dynamics

Biotin is very important for the survival of Mycobacterium tuberculosis. 7,8-Diamino pelargonic acid aminotransaminase (DAPA) is a transaminase enzyme involved in the biosynthesis of biotin. The benzothiazole title compounds were investigated for their in vitro anti-tubercular activity against two tubercular strains: H37Rv (ATCC 25,177) and MDR-MTB (multidrug-resistant M. tuberculosis, resistant to isoniazid, rifampicin, and ethambutol) by an agar incorporation method. The possible binding mode and predicted affinity were computed using a molecular docking study. Among the synthesized compounds in the series, the title compound {2-(benzo[d]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone was found to exhibit significant activity with minimum inhibitory concentrations of 1 μg/mL and 2 μg/mL against H37Rv and MDR-MTB, respectively; this compound showed the highest binding affinity (–24.75 kcal/mol) as well.