Phytochemical Studies on Medicinally Important Plants

药用植物的植物化学研究

基本信息

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

项目摘要

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）化学是由于其巨大的化学多样性而导致药物发现过程的铅化合物的主要贡献者之一。该过程的一个方面是鉴定具有抑制酶的活性的NP。对人类生命必不可少的酶进行生化过程，包括代谢，细胞信号转导，细胞循环和发育。这些生化系统中的故障通常会导致疾病，这可能是由于所涉及的酶的功能障碍/过表达/过度激活引起的。对分子水平的疾病的理解为诊所提供了多种酶抑制剂。例如，降低胆固醇的洛瓦替汀通过抑制酶（3S） - 羟基甲基戊二酰辅酶A还原酶的活性来起作用，它参与其生物合成。这项研究的目的是化学研究民族医学植物，这是各种各样有价值的NP的来源，以识别使其活跃的生物活性NP。 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还原酶（PFENR），抗肌细菌结核病Enoyl-ACP还原酶（MTENR）和抗肾素活性。据报道，所有这些酶（ACHE，ACHE，ALPHA-葡萄糖苷酶，GST，PFENR，MTENR和RENIN）均参与阿尔茨海默氏病/帕金森氏病的发病机理，糖尿病，糖尿病，改善了抗癌化疗，抗癌化疗，疟疾，TB和高血压。拟议的NP研究将验证其民族医学的使用，并有助于鉴定出抑制与上述疾病发病机理的新型NP，作为其分子靶标。拟议的研究的主要目标是确定：（i）使用生物活性和代谢组学分析方法的结合使用上述植物中的生物活性NP；（ii）内生真菌作为这些NP的替代来源；（iii）并研究其结构活性关系。这项跨学科研究集成了晚期化学仪器方法（HPLC，NMR光谱和LC-MS技术，用于NP的纯化和鉴定），微生物反应，合成有机化学，计算化学，生化化学和微生物学。在进行这项研究时，将对许多加拿大机构（包括生物技术，食品，化学或制药行业）的科学家进行培训。这项发现补助金的成功完成将为新的NP提供治疗活动，这对加拿大的健康有益。