Phytochemical Studies on Medicinally Important Plants

药用植物的植物化学研究

• 批准号: RGPIN-2015-04743
• 负责人: Ata, Athar
• 金额: $ 2.04万
• 依托单位: University of Winnipeg
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630204
• 关键词: Phytochemical; Studies; Medicinally; Important; Plants

Natural product (NP) chemistry is one of the major contributors of lead compounds to the drug discovery process due to its enormous chemical diversity. One aspect of this process is the identification of NPs with enzyme-inhibiting activities. Enzymes, essential to human life, perform biochemical processes including metabolism, cellular signal transduction, cell cycling, and development. Malfunction in these biochemical systems often leads to disease that can be caused by the dysfunction/overexpression/hyperactivation of the enzymes involved. An understanding of diseases at the molecular level has provided several enzyme inhibitors in clinics. For instance, lovastatin, a cholesterol-lowering agent, works by inhibiting the activity of enzyme (3S)-hydroxymethylglutaryl- coenzyme A reductase, involved in its biosynthesis. The purpose of this research is to chemically investigate ethnomedicinal plants, a source of a wide array of valuable NPs, to identify bioactive NPs that make them active. We have collected several plants from the Prairie Provinces of Canada and South Africa based on their ethnomedical uses by traditional healers to treat various ailments and their crude extracts exhibited various enzyme inhibitory activities including anti-acetylcholinesterase (AChE), anti-glutathione S-transferase (GST), anti-alpha-glucosidase, anti-Plasmodium falciparum Enoyl-ACP reductase (PfENR), anti-Mycobacterium tuberculosis Enoyl-ACP reductase (MtENR) and anti-renin activities. All of these enzymes (AChE, alpha-glucosidase, GST, PfENR, MtENR and renin) are reported to be involved in the pathogenesis of Alzheimer's disease/Parkinson's disease, diabetes, improving anti-cancer chemotherapy, malaria, TB and hypertension, respectively. The proposed NP research will validate their ethnomedicinal use and help to identify novel NPs that inhibit the enzymes, involved in the pathogenesis of aforementioned diseases, as their molecular target. The major objectives of the proposed research are to identify: (i) lead bioactive NPs from aforementioned plants using a combination of bioactivity and metabolomics profiling approach; (ii) endophytic fungi as an alternative source of these NPs; (iii) and to study their structure-activity relationships. This interdisciplinary research integrates advanced chemical instrumentation methods (HPLC, NMR spectroscopic and LC-MS techniques for the purification and identification of NPs), microbial reactions, synthetic organic chemistry, computational chemistry, biochemistry and microbiology. In carrying out this research, students will be trained as future scientists for many Canadian institutions including biotechnological, food, chemical or pharmaceutical industries. The successful completion of this discovery grant will provide new NPs with therapeutic activities that will be of benefit to Canadian's health.

天然产物（NP）化学因其巨大的化学多样性而成为药物发现过程中先导化合物的主要贡献者之一。这一过程的一个方面是鉴定具有酶抑制活性的纳米粒子。酶对人类生命至关重要，执行包括新陈代谢、细胞信号转导、细胞循环和发育在内的生化过程。这些生化系统的故障通常会导致疾病，这些疾病可能是由所涉及的酶的功能障碍/过度表达/过度激活引起的。对分子水平疾病的了解为临床提供了多种酶抑制剂。例如，洛伐他汀是一种降胆固醇剂，通过抑制参与其生物合成的 (3S)-羟甲基戊二酰辅酶 A 还原酶的活性来发挥作用。本研究的目的是对民族药用植物（多种有价值的纳米颗粒的来源）进行化学研究，以确定使其具有活性的生物活性纳米颗粒。我们根据传统治疗师治疗各种疾病的民族医学用途，从加拿大和南非的草原省收集了几种植物，其粗提物表现出多种酶抑制活性，包括抗乙酰胆碱酯酶 (AChE)、抗谷胱甘肽 S-转移酶 ( GST)、抗α-葡萄糖苷酶、抗恶性疟原虫烯酰-ACP 还原酶 (PfENR)、抗分枝杆菌结核烯酰 ACP 还原酶 (MtENR) 和抗肾素活性。据报道，所有这些酶（AChE、α-葡萄糖苷酶、GST、PfENR、MtENR 和肾素）分别与阿尔茨海默病/帕金森病、糖尿病、改善抗癌化疗、疟疾、结核病和高血压的发病机制有关。拟议的纳米颗粒研究将验证它们的民族医学用途，并帮助识别抑制参与上述疾病发病机制的酶的新型纳米颗粒作为其分子靶点。拟议研究的主要目标是确定：（i）结合生物活性和代谢组学分析方法，从上述植物中提取具有生物活性的纳米粒子； (ii) 内生真菌作为这些纳米颗粒的替代来源； (iii) 并研究它们的结构-活性关系。这项跨学科研究整合了先进的化学仪器方法（用于纯化和鉴定纳米颗粒的高效液相色谱、核磁共振波谱和LC-MS技术）、微生物反应、有机合成化学、计算化学、生物化学和微生物学。在进行这项研究时，学生将接受培训，成为许多加拿大机构的未来科学家，包括生物技术、食品、化学或制药行业。这项发现资助的成功完成将为新的纳米粒子提供治疗活性，这将有益于加拿大的健康。