Bioorganic & Medicinal Chemistry Letters最新文献

Discovery of a selective and potent inhibitor of c-Jun N-terminal kinase 1 with anti-pulmonary fibrosis effect

IF 2.5 4区医学

Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-11-26 DOI: 10.1016/j.bmcl.2024.130044

Shuhua Ren , Fengling Liu , Man Chi , Jinfeng Liu , Yi Huang , Weiwei Huang , Wenjing Gu , Yaxia Yuan , Shurong Hou , Xiabin Chen , Lei Ma

引用次数: 0

Brominated chalcones as promising antileishmanial agents

IF 2.5 4区医学

Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-11-26 DOI: 10.1016/j.bmcl.2024.130042

Tayssa S.A. Barreto , Tamiris A.C. Santos , Audrey R.S.T. Silva , Emmanoel V. Costa , Liciane A. Pinheiro , Roberta P.M. Fernandes , Ricardo Scher , Péricles B. Alves

{"title":"Brominated chalcones as promising antileishmanial agents","authors":"Tayssa S.A. Barreto , Tamiris A.C. Santos , Audrey R.S.T. Silva , Emmanoel V. Costa , Liciane A. Pinheiro , Roberta P.M. Fernandes , Ricardo Scher , Péricles B. Alves","doi":"10.1016/j.bmcl.2024.130042","DOIUrl":"10.1016/j.bmcl.2024.130042","url":null,"abstract":"<div><div>Leishmaniasis is a group of diseases caused by protozoa of the genus <em>Leishmania</em>. They are considered neglected diseases and are endemic to tropical and subtropical regions, affecting thousands of people annually. Leishmaniasis has a wide global distribution, present on four continents. Various drugs have been used to control leishmaniasis; however, obstacles such as high toxicity to patients and the occurrence of resistance have led to the search for alternatives. Chalcones are α, β-unsaturated ketones that can occur in the secondary metabolism of plants or can be obtained through organic synthesis. In this study, 21 chalcones brominated were synthesized via the Claisen-Schmidt condensation synthesis and characterized by UHRMS and NMR. The biological activity was evaluated for antiprotozoal potential against <em>Leishmania amazonensis</em> and cytotoxicity against L929 fibroblasts. Eighteen chalcones showed viability inhibition rates above 80 % at a concentration of 50 µM. Six chalcones demonstrated IC50 values ranging from 6.33 ± 0.70 µM to 23.95 ± 2.94 µM and maintained 70 % viability in L929 fibroblasts at 50 µM. The (<em>E</em>)-1-(4-bromophenyl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one, with a trimethoxylation at positions 2, 4, and 5 of ring B and a bromine substituent at position 4 of ring A, exhibited the lowest IC50 value (6.33 µM). These results indicate that these brominated chalcones have potential for studies aiming at the development of new drugs for leishmaniasis control.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"116 ","pages":"Article 130042"},"PeriodicalIF":2.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

(E)-3-(3-([1,1'-Biphenyl]-4-yl)-1-phenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-ones inducing reactive oxygen species generation through glutathione depletion.

IF 2.5 4区医学

Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-11-26 DOI: 10.1016/j.bmcl.2024.130043

Youngshim Lee, Seunghyun Ahn, Euitaek Jung, Yoongho Lim, Dongsoo Koh, Dong-Ho Bae, Soon Young Shin

{"title":"(E)-3-(3-([1,1'-Biphenyl]-4-yl)-1-phenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-ones inducing reactive oxygen species generation through glutathione depletion.","authors":"Youngshim Lee, Seunghyun Ahn, Euitaek Jung, Yoongho Lim, Dongsoo Koh, Dong-Ho Bae, Soon Young Shin","doi":"10.1016/j.bmcl.2024.130043","DOIUrl":"https://doi.org/10.1016/j.bmcl.2024.130043","url":null,"abstract":"<p><p>The accumulation of reactive oxygen species (ROS) disrupts reduction-oxidation homeostasis, which can result in damage to cancer cells. To identify the compounds generating ROS, compounds containing Michael acceptors were designed because they are suggested to be critical for ROS elevation via glutathione depletion. Twelve (E)-3-(3-([1,1'-biphenyl]-4-yl)-1-phenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-ones were synthesized and identified using nuclear magnetic resonance spectroscopy and mass spectrometry. Intracellular ROS levels induced by treatment with the compounds were determined using fluorescence microscopy with the oxidant-sensing fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate. We selected compound 9, which showed the highest activity, and performed further biological experiments, including glutathione depletion and apoptosis assays, using MIA PaCa-2 pancreatic cancer cells. Additionally, the reason why the intracellular ROS level by compound 9 was lower than that of menadione used as a control was explained through in silico docking experiments. Our findings suggest that compound 9 has the potential to act as an anticancer agent by inducing ROS generation through the depletion of intracellular glutathione.</p>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":" ","pages":"130043"},"PeriodicalIF":2.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis, X-ray studies and antiproliferative activity of novel lasalocid amides. 新型 lasalocid 酰胺的合成、X 射线研究和抗增殖活性。

IF 2.5 4区医学

Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-11-25 DOI: 10.1016/j.bmcl.2024.130041

Michał Sulik, Zbigniew Kubis, Dagmara Kłopotowska, Jan Janczak, Joanna Wietrzyk, Adam Huczyński

{"title":"Synthesis, X-ray studies and antiproliferative activity of novel lasalocid amides.","authors":"Michał Sulik, Zbigniew Kubis, Dagmara Kłopotowska, Jan Janczak, Joanna Wietrzyk, Adam Huczyński","doi":"10.1016/j.bmcl.2024.130041","DOIUrl":"https://doi.org/10.1016/j.bmcl.2024.130041","url":null,"abstract":"<p><p>Seeking new drug candidates among compounds of natural origin is an effective and widely used method of fighting various diseases, especially cancer. Lasalocid acid is one of the naturally occurring polyether ionophore antibiotics, which also exhibits interesting anticancer activity. Therefore, to expand the knowledge about the anticancer properties of lasalocid derivatives, a series of its new amides were synthesized and their antiproliferative activity against cancer cell lines was studied. Amides 7-9 with an aromatic substituent, displayed potent antiproliferative activity (IC<sub>50</sub>: 0.84-5.18 μM) and demonstrated a good selectivity index (SI: 1.4-15.3). Furthermore, almost all of lasalocid amides overcame the drug resistance of the doxorubicin-resistant cancer cell line (LoVo/DX). Because the biological activity of ionophores is strictly connected with their ability to transport the Na<sup>+</sup> cation through lipid bilayers, the crystal structure of the complex of compound 8 with the Na<sup>+</sup> cation was resolved. Lasalocid amides exhibit a pseudocyclic structure and are able to coordinate the Na<sup>+</sup> cation.</p>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":" ","pages":"130041"},"PeriodicalIF":2.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of drimanyl indole fragments of drimentine alkaloids and their antibacterial activities drimanyl indole fragments of drimentine alkaloids and their antibacterial activities.

IF 2.5 4区医学

Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-11-24 DOI: 10.1016/j.bmcl.2024.130040

Jili Feng , Nini Qu , Summia Kalsoom , Zunjun Zhou , Shiyi Zhang , Zhe Cui , Chongmin Zhong , Miaofeng Ma

引用次数: 0

Design, synthesis and biological evaluation of alginate oligosaccharide derivatives 海藻酸寡糖衍生物的设计、合成和生物学评价。

IF 2.5 4区医学

Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-11-23 DOI: 10.1016/j.bmcl.2024.130039

Wenkang Guo , Manchun Chen , Changjie Zou , Weizhi Liu , Weidong Wang , Heyong Gao

引用次数: 0

Recent advances of selenized tubulin inhibitors in cancer therapy 硒化微管蛋白抑制剂在癌症治疗中的最新进展。

IF 2.5 4区医学

Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-11-22 DOI: 10.1016/j.bmcl.2024.130037

Yong-Chang Zhao , Liang-Qing Yan , Yuan Xu

引用次数: 0

Discovery of novel cyclopentane carboxylic acids as potent and selective inhibitors of NaV1.7 发现新型环戊烷羧酸作为 NaV1.7 的强效选择性抑制剂。

IF 2.5 4区医学

Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-11-22 DOI: 10.1016/j.bmcl.2024.130033

Shaoyi Sun , Sultan Chowdhury , Ivan Hemeon , Abid Hasan , Michael S. Wilson , Phillipe Bergeron , Qi Jia , Alla Y. Zenova , Mike E. Grimwood , Wei Gong , Shannon M. Decker , Paul Bichler , Jean-Christophe Andrez , Thilo Focken , Theresa Ngyuen , Jiuxiang Zhu , Andrew D. White , Girish Bankar , Sarah Howard , Elaine Chang , Christoph M. Dehnhardt

{"title":"Discovery of novel cyclopentane carboxylic acids as potent and selective inhibitors of NaV1.7","authors":"Shaoyi Sun , Sultan Chowdhury , Ivan Hemeon , Abid Hasan , Michael S. Wilson , Phillipe Bergeron , Qi Jia , Alla Y. Zenova , Mike E. Grimwood , Wei Gong , Shannon M. Decker , Paul Bichler , Jean-Christophe Andrez , Thilo Focken , Theresa Ngyuen , Jiuxiang Zhu , Andrew D. White , Girish Bankar , Sarah Howard , Elaine Chang , Christoph M. Dehnhardt","doi":"10.1016/j.bmcl.2024.130033","DOIUrl":"10.1016/j.bmcl.2024.130033","url":null,"abstract":"<div><div>Discovery efforts leading to the identification of cyclopentane carboxylic acid <strong>31</strong>, a potent inhibitor of Na<sub>V</sub>1.7 that showed high selectivity over Na<sub>V</sub>1.5 and exhibited robust analgesic effects in an inherited erythromelalgia (IEM) transgenic mouse assay, are described herein. Key design elements that culminated in the discovery of <strong>31</strong> include exploration of proline substituents, replacement of the proline warhead with cyclopentane carboxylic acid, that led to significantly boosted Na<sub>V</sub>1.7 potency, and replacement of the metabolically labile adamantane motif with the 2,6-dichlorobenzyl substituted piperidine system, that addressed metabolic instability and led to a significant improvement in PK.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"116 ","pages":"Article 130033"},"PeriodicalIF":2.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design, synthesis and bioactivity evaluation of cinnamic acid derivatives as potential anti-inflammatory agents against LPS-induced acute lung injury 肉桂酸衍生物的设计、合成和生物活性评估，作为抗 LPS 诱导的急性肺损伤的潜在抗炎剂。

IF 2.5 4区医学

Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-11-22 DOI: 10.1016/j.bmcl.2024.130036

Pengqin Chen , Pan Chen , Xiemin Wang

引用次数: 0

Synthesis and evaluation of anti-Giardia activity of oseltamivir analogs 奥司他韦类似物的合成和抗贾第虫活性评估。

IF 2.5 4区医学

Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-11-21 DOI: 10.1016/j.bmcl.2024.130035

Harrison W. VanKoten , Breanna C. Pence , James R. Klinkenberg , Siddhartha Das , Steven E. Patterson

引用次数: 0