吡咯[1,2-a]喹啉衍生物的抗阿尔茨海默病和抗真菌活性

IF 0.2
Pramod N Patil, Vijayakumar Uppar, Basavaraj Padmashali, Rangappa Keri
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引用次数: 0

摘要

精神科医生描述了大脑中的蛋白质沉积会导致各种疾病,如大脑、功能、生理功能障碍和神经退行性疾病。虽然阿尔茨海默病是可以检测到的,但它的治疗仍然无法实现。每年有超过460万的新患者被记录在案,他们受到阿尔茨海默病的影响,目前只有少数药物用于治疗副作用。因此,临床需要新药的设计和开发。另一方面,尽管抗真菌疗法在过去三十年中有所发展,但抗真菌耐药性仍然是主要原因。经常使用不适当的抗菌素已成为21世纪全球的一个主要卫生保健问题,并被称为“现代医学面临的无声海啸”。据估计,每年有超过800万人死于真菌感染,这为开发新型抗真菌药物提供了前景。在本研究中,我们对合成的二甲基-1-(4-取代苯甲酰)-5-甲基吡咯[1,2-a]喹啉-2,3-二羧酸酯1a-c和乙基-1-(4-取代苯甲酰)5-甲基吡咯[1,2-a]喹啉-3-羧酸酯1d-f进行了体外抗真菌和抗阿尔茨海默病活性的评价。以K2CO3和DMF为溶剂,分别用二甲基乙炔二羧酸酯和丙酸乙酯对季盐进行1,3-偶极环加成反应,得到了衍生物1a-f。其中,化合物1a、1d和1e的IC50值分别为0.28、0.32和0.30 μM,抑菌能力最强。另一方面,衍生物也被筛选为具有中等活性的抗真菌活性,而1a和1f衍生物表现出良好的活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anti-Alzheimer’s and Anti-Fungal Activities of Pyrrolo[1,2-a] Quinoline Derivatives
Psychiatrists have described the protein deposits in the brain that causes various diseases such as cerebral, functional,physiological dysfunction, and neurodegenerative diseases. Although Alzheimer's disease is detectable, its treatment remainsunattainable. More than 4.6 million new patients are recorded yearly, who are affected by Alzheimer's disease and only a fewdrugs are currently in use for treatment with side effects. Hence, there is a clinical need for new drugs, design, and development.On the other hand, despite the development of antifungal therapeutics over the last three decades, antifungal resistance is still amajor cause. Regularly using inappropriate antimicrobials has become a major healthcare problem globally in the 21st century andhas been titled a "silent tsunami facing modern medicine." It has been estimated that over 8,000,000 die yearly, which providesscope for developing novel antifungal drugs. In this research paper, we describe the synthesized dimethyl-1-(4-substitutedbenzoyl)-5-methylpyrrolo[1,2-a] quinoline-2,3-dicarboxylate 1a-c and ethyl-1-(4-substituted benzoyl) 5-methylpyrrolo[1,2-a]quinoline-3-carboxylate 1d-f were evaluated for in vitro antifungal and anti-Alzheimer’s activities. The derivatives1a-f wereobtained by 1,3-dipolar cycloaddition reaction by treating quaternary salt with dimethyl acetylene dicarboxylate and ethylpropiolate respectively, in the presence of K2CO3 and DMF as a solvent. Among all compounds, 1a, 1d, and 1e showed thehighest inhibitory capacity with IC50 values of 0.28, 0.32, and 0.30 μM, respectively. On the other hand, derivatives were alsoscreened for antifungal activity that displayed moderate activity, whereas 1a and 1f derivatives showed good activity.
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