Anthelmintic

驱虫药
  • 文章类型: Journal Article
    扭曲血吸虫是一种影响绵羊和山羊的高致病性吸血寄生虫,造成重大经济损失。随着对常规驱虫药的抵抗力增加,探索基于植物的替代品至关重要。体外,研究表明,Peruvin和hentriacontane/1-nonacosanol,从蒿属(菊科)中分离,可能会协同控制扭曲的黄鼠。然而,它们的体内功效和安全性尚未确定。这项研究评估了这些化合物的驱虫活性和健康效应及其在Merionesunguiculatus(沙鼠)中的协同混合物。使用开放柱色谱法分离化合物并通过光谱技术鉴定。在地塞米松治疗后,沙鼠被人工感染以增强感染。通过减少胃中的幼虫来评估驱虫活性,使用血液化学分析仪的血液生化参数,以及肾脏和肝脏组织的解剖病理学变化。Peruvin(0.4mg/kg)和hentriacontane/1-nonacosanol(2.60mg/kg)的杀幼虫率降低了84.86%和74.05%,分别,而它们的协同混合物(0.08/0.0017mg/kg)导致100%的减少。组织病理学分析显示轻微的炎症和蛋白变性,主要影响肝脏。Peruvin治疗组表现出明显的肾脏损害,而两种化合物的肝脏改变相似。虽然有效,需要进一步的研究来优化给药并确保安全.
    Haemonchus contortus is a highly pathogenic blood-feeding parasite affecting sheep and goats, leading to significant economic losses. With increasing resistance to conventional anthelmintics, exploring plant-based alternatives is crucial. In vitro, studies suggest that peruvin and hentriacontane/1-nonacosanol, isolated from Artemisia cina (Asteraceae), may synergistically control Haemonchus contortus. However, their in vivo efficacy and safety are unestablished. This study evaluated these compounds\' anthelmintic activity and health effects and their synergistic mixture in Meriones unguiculatus (gerbils). The compounds were isolated using open-column chromatography and identified by spectroscopic techniques. Gerbils were artificially infected with H. contortus following dexamethasone treatment to enhance infection. Anthelmintic activity was assessed by larval reduction in the stomach, blood biochemical parameters using a blood chemistry analyzer, and the anatomopathological changes in kidney and liver tissues. Peruvin (0.4 mg/kg) and hentriacontane/1-nonacosanol (2.60 mg/kg) achieved larvicidal reductions of 84.86 % and 74.05 %, respectively, while their synergistic mixture (0.08/0.0017 mg/kg) resulted in a 100 % reduction. Histopathological analysis revealed minor inflammation and albuminous degeneration, primarily affecting the liver. The peruvin-treated group showed notable kidney damage, while hepatic alterations were similar across both compounds. Although effective, further research is needed to optimize dosing and ensure safety.
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  • 文章类型: Journal Article
    在过去的十年里,鸡肉产量有所增加,导致对家禽产品的更人性化选择的需求随之增加,包括无笼,自由范围,有机肉和鸡蛋。这些畜牧业的变化,然而,伴随着a虫感染的患病率增加,这可能导致鸡的临床疾病,以及偶尔出现的虫子在鸡蛋。此外,在紧密相关的火鸡蠕虫中,驱虫抗性的发展突显了对密切监测驱虫治疗计划的需要。手动粪便卵计数(FECs)可能很耗时,需要专业培训。因此,本研究旨在验证一种用于检测和定量鸡粪便中蛋鸡的自动FEC系统。对于方法之间的精度和相关性,将使用Parasight系统(PS)的自动计数与传统的手动McMaster计数进行了比较。总的来说,对20个个体样品进行10次重复计数,每种方法共进行200次计数.一个强大的,方法之间存在统计学上显著的相关性(R2=0.7879,P<0.0001),与手动McMaster计数相比,PS计数更多的鸡蛋,并且具有统计学上更高的精度(P=0.0391)。这项研究表明,PS是执行A.galliFECs的良好替代方法,并提供了一种新的工具,可用于鸡操作中的蠕虫治疗和控制程序。
    Chicken production has increased over the past decade, resulting in a concomitant rise in the demand for more humane options for poultry products including cage-free, free-range, and organic meat and eggs. These husbandry changes, however, have come hand-in-hand with increased prevalence of Ascaridia galli infection, which can cause clinical disease in chickens as well as the occasional appearance of worms in eggs. Additionally, development of anthelmintic resistance in closely related helminths of turkeys highlights the need for closely monitored anthelmintic treatment programs. Manual faecal egg counts (FECs) can be time-consuming and require specialist training. As such, this study sought to validate an automated FEC system for use in detection and quantification of A. galli eggs in chicken faeces. Automated counts using the Parasight System (PS) were compared to traditional manual McMaster counting for both precision and correlation between methods. Overall, ten repeated counts were performed on twenty individual samples for a total of 200 counts performed for each method. A strong, statistically significant correlation was found between methods (R2 = 0.7879, P < 0.0001), and PS counted more eggs and performed with statistically significant higher precision (P = 0.0391) than manual McMaster counting. This study suggests that PS is a good alternative method for performing A. galli FECs and provides a new tool for use in helminth treatment and control programs in chicken operations.
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  • 文章类型: Journal Article
    被忽视的热带病血吸虫病感染了全球2亿多人,仅使用一种广谱抗寄生虫药物(吡喹酮)进行治疗。如果出现吡喹酮耐药或治疗失败,则需要替代药物。在动物模型和人体临床试验中显示出疗效的一个有希望的线索是苯二氮卓美甲安定,由罗氏在20世纪70年代发现。由于剂量限制的镇静剂副作用,Meclonazepam未上市。然而,引起镇静作用(GABAAR)的人类目标米氯西泮与引起蠕虫死亡的寄生虫目标不是直系同源的。因此,我们感兴趣的是,是否可以改变美甲安定的结构,以产生不引起宿主镇静作用的抗寄生虫苯二氮卓类药物。我们合成了18种在苯并二氮杂环系统上不同位置进行修饰的米氯西epa衍生物,并测试了它们的体外抗寄生虫活性。这确定了五种在小鼠模型中进行体内筛选的化合物,其中两种治疗寄生虫感染的效力与米氯西泮相当。当将这两种化合物施用于在旋转杆测试中运行的小鼠时,两者的镇静作用都不如甲氯西泮。这些发现证明了以下概念的证明:可以设计具有改善的治疗指数的meclonazepam类似物,并指向苯二氮杂环系统的C3位置作为进一步的结构活性探索的逻辑位点,以进一步优化该化学系列。
    The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad-spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resistance or treatment failure. One promising lead that has shown efficacy in animal models and a human clinical trial is the benzodiazepine meclonazepam, discovered by Roche in the 1970s. Meclonazepam was not brought to market because of dose-limiting sedative side effects. However, the human target of meclonazepam that causes sedation (GABAARs) is not orthologous to the parasite targets that cause worm death. Therefore, we were interested in whether the structure of meclonazepam could be modified to produce antiparasitic benzodiazepines that do not cause host sedation. We synthesized 18 meclonazepam derivatives with modifications at different positions on the benzodiazepine ring system and tested them for in vitro antiparasitic activity. This identified five compounds that progressed to in vivo screening in a murine model, two of which cured parasite infections with comparable potency to meclonazepam. When these two compounds were administered to mice that were run on the rotarod test, both were less sedating than meclonazepam. These findings demonstrate the proof of concept that meclonazepam analogs can be designed with an improved therapeutic index and point to the C3 position of the benzodiazepine ring system as a logical site for further structure-activity exploration to further optimize this chemical series.
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  • 文章类型: Journal Article
    本研究描述了一种环保的NBS辅助区域选择性合成新的5-酰基官能化的5-酰基官能化的2-(1H-吡唑-1-基)噻唑,方法是将3,5-二甲基-1H-吡唑-1-硫代酰胺与不对称的1,3-二酮缩合在无溶剂条件下。新合成化合物的结构阐明是使用各种光谱技术完成的。FTIR,NMR和质谱。检查了所有新合成的化合物对致病性革兰氏阳性和革兰氏阴性细菌和真菌物种的体外抗菌潜力,以及对Pheretimaposhuma蚯蚓的驱虫活性。抗微生物活性的结果表明,所有测试的化合物3a-j都显示出优异的抗微生物潜力,特别是针对金黄色葡萄球菌。还观察到化合物3e和3i(MIC=62.5μg/mL)对大肠杆菌显示出更大的效力,而化合物3a和3h(MIC=50μg/mL和62.5μg/mL)对铜绿假单胞菌表现出更好的活性,而化合物3i(MIC=62.5μg/mL)与标准药物氨苄西林(MIC=100μg/mL)相比对化脓性链球菌表现出更好的活性。化合物3e和3j显示出显著的抗真菌和驱虫活性。为了找出目标化合物与目标蛋白的结合相互作用和化合物的药代动力学参数,还进行了涉及分子对接研究和ADMET预测的计算机模拟研究.
    The present study describes an eco-friendly NBS-assisted regioselective synthesis of new 5-acylfunctionalized 5-acylfunctionalized 2-(1H-pyrazol-1-yl)thiazoles by condensation of 3,5-dimethyl-1H-pyrazole-1-carbothioamide with unsymmetrical 1,3-diketones under solvent-free conditions. The structural elucidation of the newly synthesized compounds was accomplished using various spectroscopic techniques viz. FTIR, NMR and mass spectrometry. All the newly synthesized compounds were examined for their in vitro antimicrobial potential against both pathogenic gram positive and gram negative bacterial and fungal species as well as anthelmintic activity against Pheretima posthuma earthworms. The results of antimicrobial activity revealed that all tested compounds 3 a-j showed excellent antimicrobial potential particularly against S. aureus. It was also observed that compounds 3 e and 3 i (MIC=62.5 μg/mL) showed greater potency against E. coli, whereas compounds 3 a and 3 h (MIC=50 μg/mL and 62.5 μg/mL) demonstrated better activity against P. aeruginosa and compound 3 i (MIC=62.5 μg/mL) exhibited superior activity against S. pyogenus when compared to standard drug Ampicillin (MIC=100μg/mL). Compound 3 e and 3 j revealed remarkable antifungal and anthelmintic activities. To find out binding interactions of target compounds with target proteins and pharmacokinetic parameters of the compounds, in silico investigations involving molecular docking studies and ADMET predictions were also performed.
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  • 文章类型: Journal Article
    尾囊病和囊虫病是由棘突引起的感染,牛带菌就是其中之一。在发展中国家,T.solium神经囊虫病占人类获得性癫痫的30%。进行这项研究是为了确定驱虫干预后Mbulu地区家猪的囊虫病患病率。该研究是在2020年3月至2021年9月期间在Mbulu区的三个农村社区中进行的,监测了社区干预。通过舌检查诊断活的猪是否存在猪囊尾蚴。并记录养猪的做法。进行Logistic回归以确定危险因素对猪感染结局的作用。我们方便地采样了510头猪;2020年采样了267头(52.4%),2021年采样了243头(47.6%)。所有的猪都通过舌法检查是否存在猪肉tape虫幼虫,43只(8.4%)猪被感染。受感染的猪中,雄性猪21头(48.8%),雌性猪22头(51.2%),2020年和2021年,tape虫幼虫的总体年患病率分别为9%和7.8%。与2020年的旱季相比,雨季发现猪感染的可能性增加了两倍(OR=2.27,95CI为1.16-7.22)。报道的养猪做法是自由放养,penned,并拴在一起,141(52.8%),64(24%),和62(23.2%),分别。在2020年访问的94个家庭中,有78个(83%)报告饮用水没有煮沸,59名(62.8%)家庭领导报告听说过头孢/囊虫病。在这项研究中,家猪的囊虫病患病率很高,季节性变化。尽管正在进行全国学校驱虫和社区驱虫计划,猪囊虫病的患病率连续两年没有显著变化.报道的猪感染意味着粪便-口腔传播与从受感染的人释放的人类tape虫卵。大多数家庭报告说,他们正在饮用可能被污染的未煮沸的饮用水。结合猪的疫苗接种和驱虫,建议进行健康教育,学校或社区驱虫,并改善养猪管理实践和一般社区用水卫生(WASH),以减轻研究社区猪肉tape虫的负担。
    Taeniosis and cysticercosis are infections caused by cestodes, Taenia solium is among them. T.solium neurocysticercosis accounts for 30% of acquired epilepsy in human in developing countries. This study was carried out to determine the prevalence of cysticercosis among domestic pigs in Mbulu district following deworming intervention. The study was conducted among three rural communities monitoring community intervention in Mbulu district between March 2020 and September 2021. Live pigs were diagnosed by lingual examination for the presence of T. solium cysticerci, and pig-rearing practices were recorded. Logistic regression was performed to determine the role of risk factors on pig infection outcome. We conveniently sampled 510 pigs; 267 (52.4%) were sampled in the year 2020 and 243 (47.6%) in 2021. All pigs were examined by lingual examination for the presence of pork tapeworm larvae, and 43 (8.4%) pigs were found to be infected. Twenty-one (48.8%) of the infected pigs were males and 22 (51.2%) were females, and the overall annual prevalence of tapeworm larvae was 9% and 7.8% for 2020 and 2021, respectively. The pigs were twice more likely to be found infected during the rainy season compared to the dry season in 2020 (OR = 2.27, 95%CI of 1.16-7.22). The reported pig-rearing practices were free-range, penned, and tethered, 141 (52.8%), 64 (24%), and 62 (23.2%), respectively. Of the 94 visited households in 2020, 78 (83%) reported drinking water without boiling, and 59 (62.8%) household leaders reported having heard about taeniosis/cysticercosis. The prevalence of cysticercosis among domestic pigs in this study was high, with seasonal variations. Despite the ongoing national school deworming and community deworming program, there was no significant change in the prevalence of cysticercosis over two consecutive years. The reported pig infections imply fecal-oral transmission with humans tapeworm eggs released from infected humans. Most households reported consuming unboiled drinking water that might be contaminated. Integrating pig vaccination and deworming, health education and school or community deworming along with improved pig management practice and general community water sanitation hygiene (WASH) are recommended to reduce the burden of pork tapeworm in the study communities.
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  • 文章类型: Journal Article
    由于对合成驱虫药的普遍抗性,药用植物作为对抗寄生虫的手段正变得越来越流行。山羊通常对驱虫治疗的反应较差,这可能会增加它们对线虫的抵抗力。为此,槲寄生天花的驱虫作用(P.槲皮素)提取物在针对山羊胃肠道寄生虫的体内研究中进行了测试。将40只自然感染混合胃肠线虫的山羊分为四组:第一组用阿苯达唑(7.5mg/kg)治疗,第二组接受单剂量的closantel(7.5mg/kg),第三组接受植物提取物(7.5mg/kg),第四组作为未处理的对照组。在第14天以及第0天(其在第一处理剂量之前)进行粪便卵计数(FEC)。根据结果,在P.quercetorum治疗组中观察到FEC百分比的最大降低(63.41%).此外,线虫寄生虫对合成药物反应不佳,尽管阿苯达唑和氯桑泰尔治疗组的FEC下降了4.72%和45.54%,分别。尽管在治疗组之间没有发现显着差异,在处理后,槲寄生疟原虫处理组显示粪便卵数显著减少。根据调查结果,一种基于quercetoum的驱虫药可能是一种可持续的替代方法,可以对抗寄生虫的侵扰。因此,需要进一步的研究来确定有效控制山羊胃肠道寄生虫所需的最佳剂量率和剂量频率。
    The use of medicinal plants as a means of combating parasites is becoming increasingly popular due to general resistance to synthetic anthelmintics. Goats typically respond less well to anthelminthic treatments, which may increase their resistance to nematodes. For this purpose, the anthelmintic effect of Pelargonium quercetorum Agnew (P. quercetorum) extract was tested in an in vivo study against gastrointestinal parasites of goats. A total of 40 goats naturally infected with mixed gastrointestinal nematode species were divided into four groups: the first group was treated with albendazole (7.5 mg/kg), the second group received a single dose of closantel (7.5 mg/kg), the third group received plant extract (7.5 mg/kg), and the fourth group served as an untreated control. Fecal egg counts (FEC) were carried out on day 14, as well as day 0, which was prior to the first treatment dose. According to the results, maximum reduction in FEC percentage was observed in P. quercetorum treated group (63.41%). Furthermore, nematode parasites responded poorly to synthetic drugs, although there was a 4.72% and 45.54% decrease in FEC in the albendazole and closantel-treated groups, respectively. Although no significant difference was found between the treatment groups, the P. quercetorum treated group showed a significant reduction in fecal egg count after treatment. Based on findings, a P. quercetorum based anthelmintic could be a sustainable alternative to combat parasite infestation. Therefore, further studies are needed to determine the optimal dose rate and frequency of doses required for effective control of gastrointestinal parasites in goats.
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  • 文章类型: Journal Article
    蠕虫病,影响全球数十亿人,构成了重大的健康问题,特别是在卫生条件不足的贫困地区。蠕虫复杂的解剖复杂性需要专门的治疗方法。目前没有针对蠕虫感染的有效疫苗。驱虫药,对于对抗这些感染至关重要,在不伤害宿主的情况下,针对寄生虫的神经肌肉功能。然而,对现有驱虫药的抗性的出现,特别是苯并咪唑,提出了日益增长的全球挑战。这篇综述深入研究了先前合成的核心驱虫支架-苯并咪唑的结构-活性关系,香豆素,吡唑啉,三唑,和其他人-阐明他们有希望的驱虫活动。了解这些新型苯并咪唑衍生物的结构-活性关系,香豆素衍生物,其他人对设计有效的驱虫药至关重要,克服阻力,并优化疗效以对抗不断升级的全球蠕虫感染负担。在本次审查中,我们涵盖了最近研究的化合物(从2019年到目前为止),这些化合物具有有希望的驱虫活性。这篇综述将有助于药理学和药物化学研究人员在该领域使用各种支架,如氨基苯并噻唑,苯并咪唑,苯并噻唑,香豆素,色烯,螺缩酮,吡唑啉,三唑,等。设计新型有效的驱虫化合物。
    Helminthiasis, affecting billions globally, poses a significant health concern, especially in impoverished regions with inadequate sanitation. The intricate anatomical complexity of helminths requires specialized treatment approaches. There is currently no effective vaccine against helminth infections. Anthelmintics, crucial for combating these infections, target neuromuscular functions in parasites without harming the host. However, the emergence of resistance to existing anthelmintics, notably benzimidazoles, presents a growing global challenge. This review delves into the structure-activity relationship of previously synthesized core anthelmintic scaffolds-Benzimidazole, coumarin, pyrazoline, triazole, and others-to elucidate their promising anthelmintic activities. Understanding the structure-activity relationship of these novel benzimidazole derivatives, Coumarin derivatives, and others is crucial in designing potent anthelmintics, overcoming resistance, and optimizing efficacy to combat the escalating global burden of helminth infections. In the present review, we cover recently studied compounds (from the year 2019 to till date) which have promising anthelmintic activity. This review will be useful for the pharmacology and medicinal chemistry researchers working in the area anthelmintics with various scaffolds like aminobenzothiazole, benzimidazole, benzothiazole, coumarin, chromene, spiroketal, pyrazoline, triazole, etc. to design novel potent anthelmintic compound.
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  • 文章类型: Journal Article
    千马华立木科思。,通常被称为针木树(Theaceae家族),在传统的Mizo药物中用于治疗人类蠕虫病,并可作为动物体外寄生虫的香脂。尽管已经通过实验研究了药用特性,它作为传统驱虫药的使用仍未被探索。本研究旨在分析华木的化学成分和抗寄生虫活性。
    使用石油醚对S.wallichi树皮提取物进行了化学分析,重点研究了次级代谢产物,氯仿,和甲醇。气相色谱-质谱(GC-MS)用于鉴定特定化合物。对四角雷利替纳进行了驱虫敏感性试验,鸡的肠道寄生虫。
    甲醇提取物产生的生物碱浓度最高,碳水化合物,糖苷,固醇,皂苷,和所有提取物中的单宁。甾醇是所有提取物中最丰富的化合物,没有黄酮类化合物。石油醚和氯仿提取物中基本上不存在次生代谢产物。GC-MS数据确定了胆盐-22-烯-21-醇是主要的类固醇成分。植物提取物以浓度依赖的方式抑制了c虫寄生虫。植物提取物的驱虫活性通过对寄生虫的外部结构的可观察到的损害而明显。
    水木树皮中的植物甾醇是其驱虫特性的原因。驱虫分子的机制和药物特性需要进一步探索。
    UNASSIGNED: Schima wallichii Korth., commonly known as the needlewood tree (family Theaceae) has therapeutic uses in traditional Mizo medicine for human helminthiasis and serves as a balm against ectoparasites in animals. Although the medicinal properties have been studied experimentally, its use as a traditional anthelmintic remains unexplored. This study aimed to analyze the chemical components and antiparasitic activity of S. wallichii.
    UNASSIGNED: The chemical analysis of S. wallichi bark extracts was conducted focusing on the secondary metabolites using petroleum ether, chloroform, and methanol. Gas chromatography-mass spectrometry (GC-MS) was used to identify the specific compounds. An anthelmintic susceptibility test was carried out against Raillietina tetragona, intestinal cestode parasite of fowl.
    UNASSIGNED: The methanol extract yielded the highest concentrations of alkaloids, carbohydrates, glycosides, sterols, saponins, and tannins among all the extracts. Sterols were the most abundant compounds in all extracts, with flavonoids being absent. Secondary metabolites were largely absent in the petroleum ether and chloroform extracts. The GC-MS data identified cholest-22-ene-21-ol as the major steroid component. The cestode parasite was inhibited in a concentration-dependent manner by the plant extract. The plant extract\'s anthelmintic activity was evident through observable damage to the parasite\'s outer structure.
    UNASSIGNED: Phytosterols in S. wallichii bark are responsible for its anthelmintic properties. The mechanism and pharmaceutical properties of the anthelmintic molecule require further exploration.
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  • 文章类型: Journal Article
    驱虫药的持续使用导致了全球性的耐药性问题。解决此问题的一个突破是利用源自农业工业废物中活性化合物的生物驱虫药。这项体内研究调查了Podang芒果(MangiferaindicaL.)果皮废物提取物用于驱虫目的的有效性,使用浓度高达5%。
    这项研究包括28只17个月大的Etawa杂交山羊。山羊被随机分为四组:阴性对照,水果皮提取物(AFPE)组,2.5%,另一组AFPE为5%,和接受伊维菌素的阳性对照。选择的山羊在暴露于扭曲的Haemonchus之前,每克的鸡蛋(EPG)数量超过1000。在为期9周的研究中的7天,给予了波当芒果的AFPE。第七天,阳性对照组给予伊维菌素。AFPE剂量取决于每公斤动物体重的平均皱胃液。喂养方案包括浓缩和狼尾草。Mott是为牲畜的营养需求而定制的。饲料消费数据,消化率,平均每日收益,粪便卵数减少百分比,身体状况评分,在整个研究过程中收集临床参数。
    在较高的治疗水平(AFPE)下,EPG和粪便卵数均有较大减少.维持消耗和消化率的预期和正常范围。虽然体重增加,FAMACHA参数显示下降。与阴性对照组相比,血红蛋白存在实质性差异(p<0.05),红细胞,阳性对照组和治疗组的血细胞比容。血尿素氮和肌酐,指示肝脏和肾脏健康,在正常范围内。
    在浓度高达5%时,Podang芒果废物提取物(AFPE)可以替代山羊的传统蠕虫药物或生物驱虫药,提高他们的生产。
    UNASSIGNED: The continuous use of anthelmintic drugs has led to global issues of resistance. One breakthrough to address this problem is the utilization of bio-anthelmintics derived from active compounds in agro-industrial waste. This in vivo study investigated the effectiveness of Podang mango (Mangifera indica L.) fruit peel waste extract for anthelmintic purposes, using concentrations up to 5%.
    UNASSIGNED: This study included 28 Etawa crossbred goats aged 17 months. Goats were randomly assigned to four groups: A negative control, an aqueous fruit peel extract (AFPE) group at 2.5%, another AFPE group at 5%, and a positive control receiving ivermectin. Goats chosen had egg per gram (EPG) counts surpassing 1000 before exposure to Haemonchus contortus. For 7 days within a 9-week study, AFPE from Podang mangoes was given. On the 7th day, the positive control group was administered ivermectin. AFPE dosage relied on the average abomasum fluid per kilogram of animal weight. The feeding regimen consisted of concentrate and Pennisetum purpureum cv. Mott is customized for the nutritional needs of livestock. Data on feed consumption, digestibility, average daily gain, percentage reduction in fecal egg count, body condition score, and clinical parameters were collected throughout the study.
    UNASSIGNED: At higher treatment levels (AFPE), there was a greater reduction in both EPG and fecal egg counts. The expected and normal ranges were maintained for consumption and digestibility. While body weight increased, FAMACHA parameters showed a decrease. Compared to the negative control group, substantial disparities (p < 0.05) existed for hemoglobin, red blood cells, and hematocrit in both the positive control and the treatment groups. Blood urea nitrogen and creatinine, indicative of liver and kidney health, were within normal ranges.
    UNASSIGNED: At a concentration of up to 5%, Podang mango waste extract (AFPE) can function as a substitute for traditional helminth medicines or bio-anthelmintics in goats, enhancing their production.
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  • 文章类型: Journal Article
    对细菌进行生物测定指导的化学研究,链霉菌sp.CMB-MRB032,从巴瑟斯特附近收集的绵羊粪便中分离出来,维多利亚,澳大利亚,产生了已知的聚酮抗生霉素A4a(1)和A2a(2)作为有效的Dirofilariaimmitis(心丝虫)微丝菌(mf)运动性(EC500.0013-0.0021µg/mL)的抑制剂,以及八肽苏鲁酰胺A(3)和新的N-甲基化类似物苏鲁酰胺K(4)。生物学数据表明,surugamides也可能表现出对抗D.immitis的活性,对来自地理上不同的澳大利亚生态系统的微生物库的GNPS分子网络分析确定了另外五个在分类学和化学上不同的苏鲁酰胺生产者。扩大一个这样的生产者的种植规模,链霉菌sp.CMB-M0112从Shorncliff收集的海洋沉积物中分离出来,昆士兰州,澳大利亚,得到3以及新的酰基-surugyidesA1-A4(5-8)。固相肽合成提供了额外的合成类似物,surugamidesS1-S3(9-11),而3的衍生化返回了半合成的surugamideS4(12)和酰基-surugyidesAS1-AS3(13-15)。天然酰基-苏鲁酰胺A3(7)和半合成酰基-苏鲁酰胺AS3(15)显示出选择性抑制D.immitismf运动(EC503.3-3.4µg/mL),然而,与抗真菌霉素1和2不同,它们对胃肠道线虫扭曲血脑L1-L3幼虫无活性(EC50>25µg/mL),对哺乳动物细胞无细胞毒性(人类结直肠癌SW620,IC50>30µg/mL).对surugamides3-15的结构-活性关系(SAR)研究表明,Lys3-ε-NH2的选择性酰化与驱虫活性相关。
    A bioassay-guided chemical investigation of a bacterium, Streptomyces sp. CMB-MRB032, isolated from sheep feces collected near Bathurst, Victoria, Australia, yielded the known polyketide antimycins A4a (1) and A2a (2) as potent inhibitors of Dirofilaria immitis (heartworm) microfilaria (mf) motility (EC50 0.0013-0.0021 µg/mL), along with the octapeptide surugamide A (3) and the new N-methylated analog surugamide K (4). With biological data suggesting surugamides may also exhibit activity against D. immitis, a GNPS molecular network analysis of a library of microbes sourced from geographically diverse Australian ecosystems identified a further five taxonomically and chemically distinct surugamide producers. Scaled-up cultivation of one such producer, Streptomyces sp. CMB-M0112 isolated from a marine sediment collected at Shorncliff, Qld, Australia, yielded 3 along with the new acyl-surugamides A1-A4 (5-8). Solid-phase peptide synthesis provided additional synthetic analogs, surugamides S1-S3 (9-11), while derivatization of 3 returned the semi-synthetic surugamide S4 (12) and acyl-surugamides AS1-AS3 (13-15). The natural acyl-surugamide A3 (7) and semi-synthetic acyl-surugamide AS3 (15) were shown to selectively inhibit D. immitis mf motility (EC50 3.3-3.4 µg/mL), however, unlike antimycins 1 and 2, were inactive against the gastrointestinal nematode Haemonchus contortus L1-L3 larvae (EC50 > 25 µg/mL) and were not cytotoxic to mammalian cells (human colorectal carcinoma SW620, IC50 > 30 µg/mL). A structure-activity relationship (SAR) study on the surugamides 3-15 revealed that selective acylation of the Lys3-ε-NH2 correlates with anthelmintic activity.
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