Suppr超能文献

传染病研究的农用化学品经验教训:新型抗耐药性抗真菌药物靶点……

Agrochemical Lessons for Infectious Disease Research: New Resistance Breaking Antifungal Hits against .

作者信息

Winter Christian, Siepe Isabella, Wise Andrew, Dorali Alain, Barrett Anthony G M, Witschel Matthias

机构信息

BASF-SE, D-67056 Ludwigshafen, Germany.

BASF-SE, D-67117 Limburgerhof, Germany.

出版信息

ACS Med Chem Lett. 2023 Jan 25;14(2):136-140. doi: 10.1021/acsmedchemlett.2c00497. eCollection 2023 Feb 9.

Abstract

Analysis of the history of the invention of the block-buster antifungal drug Fluconazole underscores the importance of agrochemical research on drug discovery and development. The multidrug resistant fungal pathogen is now responsible for serious morbidity and mortality among immuno-compromised and long-term resident hospital patients globally. New drugs against are urgently needed. A focused screening of 1487 fungicides from the BASF agrochemical collection gave several potent inhibitors of with yet noncommercialized modes of action. The hits showed only minor activity loss against the azole-resistant strain CDC 0385 and low to moderate cytotoxicity to human HepG2 cells. Aminopyrimidine showed high activity against resistant strains and selectivity in a HepG2 cells assay and is a potential hit candidate for further optimization.

摘要

对抗真菌重磅药物氟康唑发明历史的分析凸显了农用化学品研究在药物发现与开发中的重要性。多重耐药真菌病原体目前在全球免疫功能低下和长期住院患者中导致严重的发病和死亡。迫切需要针对该病原体的新药。对巴斯夫农用化学品库中的1487种杀菌剂进行的重点筛选得到了几种具有尚未商业化作用模式的强效该病原体抑制剂。这些命中化合物对唑类耐药菌株CDC 0385仅表现出轻微的活性损失,对人肝癌细胞HepG2的细胞毒性低至中等。氨基嘧啶在HepG2细胞试验中对耐药菌株表现出高活性和选择性,是进一步优化的潜在命中候选物。

相似文献

1
Agrochemical Lessons for Infectious Disease Research: New Resistance Breaking Antifungal Hits against .
ACS Med Chem Lett. 2023 Jan 25;14(2):136-140. doi: 10.1021/acsmedchemlett.2c00497. eCollection 2023 Feb 9.
2
Synergistic interactions of sulfamethoxazole and azole antifungal drugs against emerging multidrug-resistant Candida auris.
Int J Antimicrob Agents. 2018 Dec;52(6):754-761. doi: 10.1016/j.ijantimicag.2018.08.016. Epub 2018 Aug 24.
4
Genomic Diversity across Candida auris Clinical Isolates Shapes Rapid Development of Antifungal Resistance and .
mBio. 2022 Aug 30;13(4):e0084222. doi: 10.1128/mbio.00842-22. Epub 2022 Jul 5.
9
Candida auris on Apples: Diversity and Clinical Significance.
mBio. 2022 Apr 26;13(2):e0051822. doi: 10.1128/mbio.00518-22. Epub 2022 Mar 31.
10
Upc2-mediated mechanisms of azole resistance in .
Microbiol Spectr. 2024 Feb 6;12(2):e0352623. doi: 10.1128/spectrum.03526-23. Epub 2024 Jan 11.

本文引用的文献

1
Latest Research Trends in Agrochemical Fungicides: Any Learnings for Pharmaceutical Antifungals?
ACS Med Chem Lett. 2022 May 16;13(6):895-903. doi: 10.1021/acsmedchemlett.2c00113. eCollection 2022 Jun 9.
3
Assessment of the rules related to gaining activity against Gram-negative bacteria.
RSC Med Chem. 2021 Mar 3;12(4):593-601. doi: 10.1039/d0md00409j. eCollection 2021 Apr 28.
4
Cork-in-bottle mechanism of inhibitor binding to mammalian complex I.
Sci Adv. 2021 May 14;7(20). doi: 10.1126/sciadv.abg4000. Print 2021 May.
5
The ubiquinone synthesis pathway is a promising drug target for Chagas disease.
PLoS One. 2021 Feb 4;16(2):e0243855. doi: 10.1371/journal.pone.0243855. eCollection 2021.
7
Antitubercular 2-Pyrazolylpyrimidinones: Structure-Activity Relationship and Mode-of-Action Studies.
J Med Chem. 2021 Jan 14;64(1):719-740. doi: 10.1021/acs.jmedchem.0c01727. Epub 2021 Jan 4.
9
On the Emergence of Candida auris: Climate Change, Azoles, Swamps, and Birds.
mBio. 2019 Jul 23;10(4):e01397-19. doi: 10.1128/mBio.01397-19.
10
Identification of Off-Patent Compounds That Present Antifungal Activity Against the Emerging Fungal Pathogen .
Front Cell Infect Microbiol. 2019 Apr 2;9:83. doi: 10.3389/fcimb.2019.00083. eCollection 2019.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验