ACS Medicinal Chemistry Letters最新文献_第5页

In This Issue, Volume 15, Issue 11 本期，第 15 卷第 11 期

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2024-11-14 DOI: 10.1021/acsmedchemlett.4c0052710.1021/acsmedchemlett.4c00527

Mark P. Farrell,

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4-Oxo-β-lactams as Covalent Inhibitors of the Mitochondrial Intramembrane Protease PARL.

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2024-11-14 eCollection Date: 2024-12-12 DOI: 10.1021/acsmedchemlett.4c00384

Shanping Ji, Kathrin Bach, Vijay Madhav Miriyala, Jan Dohnálek, Miguel Riopedre-Fernandez, Martin Lepšík, Merel van de Plassche, Roeland Vanhoutte, Marta Barniol-Xicota, Rui Moreira, Kvido Strisovsky, Steven H L Verhelst

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4-Oxo-β-lactams as Covalent Inhibitors of the Mitochondrial Intramembrane Protease PARL

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2024-11-14 DOI: 10.1021/acsmedchemlett.4c0038410.1021/acsmedchemlett.4c00384

Shanping Ji, Kathrin Bach, Vijay Madhav Miriyala, Jan Dohnálek, Miguel Riopedre-Fernandez, Martin Lepšík, Merel van de Plassche, Roeland Vanhoutte, Marta Barniol-Xicota, Rui Moreira, Kvido Strisovsky* and Steven H. L. Verhelst*,

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Chemical Synthesis and Antifibrotic Properties of (±)-Cochlearol T, (±)-Ganocochlearin A, and (±)-Cochlearol Y.

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2024-11-12 eCollection Date: 2024-12-12 DOI: 10.1021/acsmedchemlett.4c00497

Badrinath N Kakde, Sung Wan An, Yaashmin Shiny Jebaraj, Sudha Neelam, Matthias T F Wolf, Uttam K Tambar

{"title":"Chemical Synthesis and Antifibrotic Properties of (±)-Cochlearol T, (±)-Ganocochlearin A, and (±)-Cochlearol Y.","authors":"Badrinath N Kakde, Sung Wan An, Yaashmin Shiny Jebaraj, Sudha Neelam, Matthias T F Wolf, Uttam K Tambar","doi":"10.1021/acsmedchemlett.4c00497","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00497","url":null,"abstract":"The cochlearols and ganocochlearins are natural products with unique antifibrotic and renoprotective activities in models of kidney disease. They represent compelling lead compounds for pharmacological intervention against kidney disease, often characterized by renal fibrosis. We report a four-step synthesis of (±)-cochlearol T (1) and the first reported syntheses of (±)-ganocochlearin A (2) and (±)-cochlearol Y (3) through a strategy that includes a Robinson annulation and unexpected oxidative aromatization. We also access tricyclic intermediate 12 that represents a formal synthesis of ganocins A-C and ganocochlearins C-D. We investigated the activity of these synthesized compounds in vitro by inducing fibrosis in a human kidney cell line with TGF-β1. The effect on fibrosis was assessed by qPCR and Western blot studies. We detected significantly lower mRNA gene and protein expression of fibrosis markers for all three natural products.","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2220-2224"},"PeriodicalIF":3.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemical Synthesis and Antifibrotic Properties of (±)-Cochlearol T, (±)-Ganocochlearin A, and (±)-Cochlearol Y

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2024-11-12 DOI: 10.1021/acsmedchemlett.4c0049710.1021/acsmedchemlett.4c00497

Badrinath N. Kakde, Sung Wan An, Yaashmin Shiny Jebaraj, Sudha Neelam, Matthias T. F. Wolf* and Uttam K. Tambar*,

{"title":"Chemical Synthesis and Antifibrotic Properties of (±)-Cochlearol T, (±)-Ganocochlearin A, and (±)-Cochlearol Y","authors":"Badrinath N. Kakde, Sung Wan An, Yaashmin Shiny Jebaraj, Sudha Neelam, Matthias T. F. Wolf* and Uttam K. Tambar*, ","doi":"10.1021/acsmedchemlett.4c0049710.1021/acsmedchemlett.4c00497","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00497https://doi.org/10.1021/acsmedchemlett.4c00497","url":null,"abstract":"The cochlearols and ganocochlearins are natural products with unique antifibrotic and renoprotective activities in models of kidney disease. They represent compelling lead compounds for pharmacological intervention against kidney disease, often characterized by renal fibrosis. We report a four-step synthesis of (±)-cochlearol T (1) and the first reported syntheses of (±)-ganocochlearin A (2) and (±)-cochlearol Y (3) through a strategy that includes a Robinson annulation and unexpected oxidative aromatization. We also access tricyclic intermediate 12 that represents a formal synthesis of ganocins A–C and ganocochlearins C–D. We investigated the activity of these synthesized compounds in vitro by inducing fibrosis in a human kidney cell line with TGF-β1. The effect on fibrosis was assessed by qPCR and Western blot studies. We detected significantly lower mRNA gene and protein expression of fibrosis markers for all three natural products.","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2220–2224 2220–2224"},"PeriodicalIF":3.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142850164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The Antiepileptic Drug Levetiracetam Inhibits Carbonic Anhydrase: In Vitro and In Silico Studies on Catalytically Active Human Isoforms.

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2024-11-11 eCollection Date: 2024-12-12 DOI: 10.1021/acsmedchemlett.4c00380

Luigi Cutarella, Mattia Mori, Claudiu T Supuran

{"title":"The Antiepileptic Drug Levetiracetam Inhibits Carbonic Anhydrase: In Vitro and In Silico Studies on Catalytically Active Human Isoforms.","authors":"Luigi Cutarella, Mattia Mori, Claudiu T Supuran","doi":"10.1021/acsmedchemlett.4c00380","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00380","url":null,"abstract":"Several antiepileptic drugs (AEDs) have been found to inhibit human carbonic anhydrases (hCAs), paving the way for repurposing AEDs for the treatment of various diseases, including cancer. Here, the hCAs inhibitory effects of levetiracetam, a highly prescribed AED that does not bear a common zinc-binding group, were investigated in vitro and in silico. Levetiracetam inhibited all tested hCAs, although with a specific profile compared to the reference acetazolamide, with remarkable efficacy against tumor-associated hCA IX and XII. Molecular docking and dynamics (MD) simulations emphasized H-bonding to the Zn(II)-coordinated water as a major anchor point for hCAs, as well as a persistent interaction within the catalytic site of hCA isoforms IX and XII compared to II, which correlates with experimental data. Our results may explain why levetiracetam is also clinically effective as an antitumor agent in patients developing epilepsy as a consequence of brain tumors.","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2133-2139"},"PeriodicalIF":3.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advanced Delivery Systems and Novel Psilocin Derivatives for Enhanced Therapeutic Applications

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2024-11-11 DOI: 10.1021/acsmedchemlett.4c0052110.1021/acsmedchemlett.4c00521

Robert B. Kargbo*,

引用次数: 0

Innovative Cancer Therapies: Targeting Oncogenic Pathways through Placental Immunology, PROTAC Technology, and Kinase Degradation.

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2024-11-11 eCollection Date: 2024-12-12 DOI: 10.1021/acsmedchemlett.4c00520

Robert B Kargbo

引用次数: 0

Targeting Cancer: A New Era in Cancer Therapy through Immune Fitness Modulation and KRAS Degradation

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2024-11-11 DOI: 10.1021/acsmedchemlett.4c0051810.1021/acsmedchemlett.4c00518

Robert B. Kargbo*,

引用次数: 0

Asymmetric Synthesis and Biological Evaluation of Both Enantiomers of 5- and 6-Boronotryptophan as Potential Boron Delivery Agents for Boron Neutron Capture Therapy

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2024-11-11 DOI: 10.1021/acsmedchemlett.4c0024110.1021/acsmedchemlett.4c00241

Michele Retini, Juulia Järvinen, Katayun Bahrami, Janne Tampio, Francesca Bartoccini, Petri Riihelä, Henna Pehkonen, Arina Värä, Tuomo Laitinen, Kristiina M. Huttunen, Jarkko Rautio, Giovanni Piersanti and Juri M. Timonen*,

{"title":"Asymmetric Synthesis and Biological Evaluation of Both Enantiomers of 5- and 6-Boronotryptophan as Potential Boron Delivery Agents for Boron Neutron Capture Therapy","authors":"Michele Retini, Juulia Järvinen, Katayun Bahrami, Janne Tampio, Francesca Bartoccini, Petri Riihelä, Henna Pehkonen, Arina Värä, Tuomo Laitinen, Kristiina M. Huttunen, Jarkko Rautio, Giovanni Piersanti and Juri M. Timonen*, ","doi":"10.1021/acsmedchemlett.4c0024110.1021/acsmedchemlett.4c00241","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00241https://doi.org/10.1021/acsmedchemlett.4c00241","url":null,"abstract":"This research investigates boronated tryptophans as potential boron delivery agents for boron neutron capture therapy (BNCT) of cancer. We synthesized both enantiomers of 5- and 6-boronotryptophans (1a and 1b) using simple and inexpensive methods. Their uptake was assessed in two human cancer cell lines, CAL27 (head and neck cancer) and U87-MG (brain cancer), and compared to l-p-boronophenylalanine (l-BPA) as a reference. To determine whether these tryptophan derivatives are substrates for large amino acid transporter 1, we performed molecular dynamics simulations to explore their transport mechanism. Our findings reveal differences in boron compound accumulation between the cancer cell lines, indicating that tryptophan derivatives could serve as effective boron carriers when the clinically used boron carrier, BPA, is ineffective.","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"15 12","pages":"2121–2128 2121–2128"},"PeriodicalIF":3.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmedchemlett.4c00241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142843110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0