Pyrazole Based Furanone Hybrids as Novel Antimalarial: A Combined Experimental, Pharmacological and Computational Study.

Q3 Psychology

Central nervous system agents in medicinal chemistry Pub Date : 2022-03-01 DOI:10.2174/1871524922666220301121811

D. Choudhary, Isha Rani, Jyoti Monga, R. Goyal, A. Husain, P. Garg, S. Khokra

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引用次数: 5

Abstract

BACKGROUND Malaria parasite strains are resistant to therapeutic effect of prophylactics medicines presently available. This resistance now poses a significant challenge to researchers within the bid to beat malaria parasitic infections. Strategies such as investigation of newer hybrid chemical entities and specified drug targets may help us to spot new efficient derivatives that bind to the parasites in a more specific manner and inhibit their growth. OBJECTIVE To scientifically perform the experimental, pharmacological, and computational studies of pyrazole-based furanone hybrids as novel antimalarial agents. METHODS A series of new furanone based pyrazole derivatives were synthesized and investigated as potential antimalarial agents by performing in vitro antimalarial activity. To get further optimization, these synthesized derivatives were virtually screened based on ADME-T filters, and molecular docking studies were also accomplished on the crystal structures of Plasmodium falciparum lactate dehydrogenase (PfLDH). Furthermore,the in-silico prediction was supported by performing an LDH assay. RESULTS The docking data suggested that the designed hybrid of furanone-pyrazole may act as PfLDH inhibitors. It was found that the results of experimental in vitro antimalarial activity and in silico analysis correlate well to each other to a good extent. The compounds (7d), (7g), and (8e) were found to be the most potent derivatives with IC50 values of 1.968, 1.983, and 2.069 µg/ml, respectively. CONCLUSION From the results, it may be concluded that compounds that are active in low doses might be adopted as a lead compound for the development of more active antimalarial agents. The synthesized compounds (7d), (7g), and (8e) exhibited good antimalarial activity with PfLDH inhibition. The best compounds can be explored further in the future for designing the potent inhibitors of PfLDH as new potent antimalarial agents.

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吡唑基呋喃酮复合物作为新型抗疟药:实验、药理学和计算的结合研究。

背景疟疾寄生虫菌株对目前可用的预防药物的治疗效果具有耐药性。这种耐药性现在对战胜疟疾寄生虫感染的研究人员构成了重大挑战。研究新的混合化学实体和特定药物靶点等策略可能有助于我们发现新的高效衍生物，这些衍生物以更特异的方式与寄生虫结合并抑制其生长。目的对吡唑类呋喃酮杂合物作为新型抗疟药物进行科学的实验、药理学和计算研究。方法合成了一系列新的呋喃酮吡唑衍生物，并通过体外抗疟活性研究了其潜在的抗疟作用。为了进一步优化，基于ADME-T过滤器对这些合成的衍生物进行了虚拟筛选，并对恶性疟原虫乳酸脱氢酶（PfLDH）的晶体结构进行了分子对接研究。此外，通过进行LDH测定来支持计算机中的预测。结果对接数据表明，所设计的呋喃酮-吡唑杂化物可能作为PfLDH抑制剂。结果表明，体外抗疟实验结果与计算机分析结果具有良好的相关性。发现化合物（7d）、（7g）和（8e）是最有效的衍生物，IC50值分别为1.968、1.983和2.069µg/ml。结论从结果可以得出结论，低剂量活性化合物可能被用作开发更具活性的抗疟药物的先导化合物。合成的化合物（7d）、（7g）和（8e）表现出良好的抗疟活性，并具有PfLDH抑制作用。未来可以进一步探索最佳化合物，以设计PfLDH的强效抑制剂作为新的强效抗疟剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Central nervous system agents in medicinal chemistry Psychology-Neuropsychology and Physiological Psychology

CiteScore

2.10

自引率

0.00%

发文量

期刊介绍： Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.