Article
Chemistry, Medicinal
Hongrui Lei, Zhi Cao, Huinan Wu, Tong Li, Xinyu Wang, Yuxiang Chen, Enlong Ma, Lixin Sun, Xin Zhai
Summary: Pharmacological targeting of the ATX/LPA axis has shown promising disease management benefits. New indole-based carbamate derivatives were synthesized, with compound 4 identified as the most potent ATX inhibitor and compound 30 showing improved pharmacokinetic properties and anti-fibrosis effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Anze Meden, Damijan Knez, Xavier Brazzolotto, Fabrice Modeste, Andrej Perdih, Anja Pislar, Masa Zorman, Maja Zorovic, Milica Denic, Stane Pajk, Marko Zivin, Florian Nachon, Stanislav Gobec
Summary: This study investigates the covalent mechanism of reversible carbamate human butyrylcholinesterase inhibitors. The results reveal that steric constraints play a crucial role in determining the covalent binding behavior and duration of action of these inhibitors. Additionally, the introduction of a clickable terminal alkyne moiety enables fluorescent labeling of plasma human butyrylcholinesterase, providing a potential novel approach for studying the tissue localization and activity of cholinesterases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Taylor Merfeld, Shuxia Peng, Bradley M. Keegan, Vincent M. Crowley, Christopher M. Brackett, Andrew Gutierrez, Nathan R. McCann, Tyelor S. Reynolds, Matthew C. Rhodes, Katherine M. Byrd, Junpeng Deng, Robert L. Matts, Brian S. J. Blagg
Summary: Hsp90 isoform-selective inhibitors have specific cellular localization, function, and client proteins, making them a new paradigm for anti-cancer drugs. The mitochondrial isoform TRAP1, which is least understood, has been studied using novel TRAP1-selective inhibitors and co-crystal structures. Compound 36 was found to be a highly selective inhibitor of TRAP1 and exhibited various effects such as client protein degradation, disruption of mitochondrial function, and alteration of cellular metabolism.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Valentina Borlandelli, Zachary Armstrong, Alba Nin-Hill, Jeroen D. C. Codee, Lluis Raich, Marta Artola, Carme Rovira, Gideon J. J. Davies, Herman S. S. Overkleeft
Summary: A new class of anticancer drugs has been discovered that selectively inhibit the activity of a protein involved in tumor growth and metastasis, providing a potential target for cancer therapy.
Article
Chemistry, Medicinal
Tong Li, Hongrui Lei, Juanjuan Yang, Zhi Cao, Yu Yang, Zimeng Liu, Ruonan Sun, Xinlian Yang, Xin Zhai
Summary: Small-molecule inhibitors targeting the ATX/lysophosphatidic acid axis have shown disease management benefits. This study designed a series of imidazo[1,2-a]pyridine compounds as ATX inhibitors, with moderate to satisfying inhibitory potency. By modifying the linker to a urea moiety, the druglikeness profile was improved. A diethanolamine derivative showed amazing inhibitory activity, comparable to positive controls. It also demonstrated antifibrotic effects in an in vivo model.
ARCHIV DER PHARMAZIE
(2022)
Article
Chemistry, Medicinal
Shuyuan Wang, Yue Xu, Yan Zhao, Shun Zhang, Min Li, Xiaowei Li, Jinzhao He, Hong Zhou, Zemei Ge, Runtao Li, Baoxue Yang
Summary: By replacing the nitro group of 11a with an acetyl group, a new UT inhibitor, 25a, was developed with significantly improved inhibitory effects on UT-B and UT-A1 in rats and mice. The metabolic stability, drug-like properties, and bioavailability of 25a were substantially enhanced compared to 11a, leading to significant improvement in diuretic activities in animal models.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Reinad R. Abu Rabah, Anusha Sebastian, Srinivasulu Vunnam, Shaista Sultan, Hamadeh Tarazi, Hanan S. Anbar, Mahmoud K. Shehata, Seyed-Omar Zaraei, Sara M. Elgendy, Salma A. Al Shamma, Hany A. Omar, Taleb H. Al-Tel, Mohammed El-Gamal
Summary: The study reports on a new series of pyrazole derivatives with potential anticancer activity. Compound 1f showed the most potent anticancer activity against various cancer cell lines, even more potent than sorafenib and SP600125. Compounds 1b, 1c, and 1h demonstrated strong anti-proliferative activity against hepatocellular carcinoma cell lines. The study also discovered two potent JNK3 inhibitors, compounds 1c and 1f, with good inhibitory effects in whole-cell assays.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jing Mi, Ying He, Jing Yang, Yi Zhou, Gaofeng Zhu, Anguo Wu, Wenmin Liu, Zhipei Sang
Summary: In this study, a series of naringenin-O-carbamate derivatives were synthesized and evaluated for the treatment of Alzheimer's disease (AD) using a multi-target-directed ligands (MTDLs) strategy. The results demonstrated that one of the compounds exhibited good antioxidant activity, enzyme inhibition, protein degradation, and anti-inflammatory effects, along with favorable drug-like property and blood-brain barrier penetration. These findings suggest that this compound has potential as a therapeutic agent for AD.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Multidisciplinary Sciences
Alessio Fragasso, Hendrik W. de Vries, John Andersson, Eli O. van der Sluis, Erik van der Giessen, Andreas Dahlin, Patrick R. Onck, Cees Dekker
Summary: This study successfully reconstituted the selective behavior of the NPC by introducing an artificial FG-Nup that mimics natural Nups, demonstrating that specific spacer sequences or spatial segregation of different FG-motif types are not needed to create selective NPCs.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Maximilian Barth, Stefan Rudolph, Jan Kampschulze, Imke Meyer zu Vilsendorf, Walburga Hanekamp, Dennis Mulac, Klaus Langer, Matthias Lehr
Summary: A series of hexafluoroisopropyl carbamates with indolylalkyl- and azaindolylalkyl-substituents were synthesized and tested for inhibition of the endocannabinoid degrading enzymes FAAH and MAGL. The compounds with alkyl chains incorporated into a piperidine ring showed selective MAGL inhibition, while an extension of the alkyl spacer resulted in dual FAAH/MAGL inhibition. The reactive hexafluoroisopropyl carbamate group was found to be mainly responsible for the inhibitory effect. Some derivatives showed slightly higher MAGL inhibition and improved physicochemical and biochemical properties compared to the known MAGL inhibitor ABX-1431.
Article
Chemistry, Organic
Amardeep Singh, Monika Diwaker, Akshata Thakur, Khemchand Surana, Manjeet Chopra, Hemant Kumar, Satyasheel Sharma
Summary: O-Carbamate assisted Palladium (II) catalyzed regioselective C-H acylation of coumarins at C-6 position with arylglyoxylic acids was achieved. The synthesized molecules showed anti-inflammatory activity, with compound 3ia being the most active in inhibiting NF-kB expression. Further studies demonstrated that carbamate-based C-6 acylated coumarin derivatives inhibited the nuclear translocation of p65, mitigating the activation of the inflammatory cascade.
Article
Neurosciences
Cuiying Peng, Yilin Wang, Zhiping Hu, Chunli Chen
Summary: The inhibition of HDAC6 has a protective effect on BBB disruption after intracerebral hemorrhage (ICH) by upregulating acetylated a-tubulin and reducing stress fiber formation, which suggests that HDAC6 could be a potential target for ICH treatment.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Chemistry, Medicinal
Nicole McNamara, Eleanor Saunders, Swapna Varghese, Rebecca Zheng, Kaylene Simpson, Devika M. Varma, Monica M. Johnson, M. Shamim Hasan Zahid, Eric M. Bachelder, Kristy M. Ainslie, Joo Hwan No, Dahae Koh, David Shum, Nirmal Das, Binita Patra, Jayasree Roy, Arindam Talukdar, Dipyman Ganguly, Malcolm McConville, Jonathan Baell
Summary: In this study, the structure-activity relationship of a novel hit compound was explored. The compound showed improved potency with low cytotoxicity against human cells, indicating its potential as a treatment for visceral leishmaniasis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yang Tian, Songhui Qin, Fang Zhang, Jing Luo, Xi He, Yi Sun, Tao Yang
Summary: The JAK2(V617F) mutation leads to the activation of JAK2 and downstream pathways, causing myelo-proliferative neoplasms (MPNs). This study presents a series of N-(4-(aminomethyl)-phenyl)-pyrimidin-2-aminederivatives as selective JAK2 inhibitors. Compound A8 showed excellent potency on JAK2 kinase and selective inhibition of JAK1, JAK3, and TYK2. It also demonstrated improved metabolic stability and bioavailability compared to the lead compound. These findings suggest that A8 is a promising JAK2 inhibitor for treating MPNs.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Moataz Shaldam, Wagdy M. Eldehna, Alessio Nocentini, Zainab M. Elsayed, Tamer M. Ibrahim, Rofaida Salem, Ramadan A. El-Domany, Clemente Capasso, Hatem A. Abdel-Aziz, Claudiu T. Supuran
Summary: This study describes the design of benzofuran-based derivatives as potential carbonic anhydrase inhibitors, with modifications in tail and spacer structures to enhance inhibitory activities against tumor-related CA isoforms. The synthesized compounds showed efficient inhibition of CA IX isoform and promising anticancer and pro-apoptotic activities towards cancer cell lines.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Mijoon Lee, Zhenzhou Chen, Brittany N. Tomlinson, Major Gooyit, Dusan Hesek, Maria Raquel Juarez, Rasheeq Nizam, Bill Boggess, Elena Lastochkin, Valerie A. Schroeder, William R. Wolter, Mark A. Suckow, Jiancun Cui, Shahriar Mobashery, Zezong Gu, Mayland Chang
ACS CHEMICAL NEUROSCIENCE
(2015)
Article
Biochemical Research Methods
Kasey J. Clear, Kara M. Harmatys, Douglas R. Rice, William R. Wolter, Mark A. Suckow, Yuzhen Wang, Mary Rusckowski, Bradley D. Smith
BIOCONJUGATE CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Edward Spink, Derong Ding, Zhihong Peng, Marc A. Boudreau, Erika Leemans, Elena Lastochkin, Wei Song, Katerina Lichtenwalter, Peter I. O'Daniel, Sebastian A. Testero, Hualiang Pi, Valerie A. Schroeder, William R. Wolter, Nuno T. Antunes, Mark A. Suckow, Sergei Vakulenko, Mayland Chang, Shahriar Mobashery
JOURNAL OF MEDICINAL CHEMISTRY
(2015)
Article
Chemistry, Multidisciplinary
Renee Bouley, Malika Kumarasiri, Zhihong Peng, Lisandro H. Otero, Wei Song, Mark A. Suckow, Valerie A. Schroeder, William R. Wolter, Elena Lastochkin, Nuno T. Antunes, Hualiang Pi, Sergei Vakulenko, Juan A. Hermoso, Mayland Chang, Shahriar Mobashery
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2015)
Article
Biochemistry & Molecular Biology
Patrick R. Gonzales, Mitchell W. Pesesky, Renee Bouley, Anna Ballard, Brent A. Biddy, Mark A. Suckow, William R. Wolter, Valerie A. Schroeder, Carey-Ann D. Burnham, Shahriar Mobashery, Mayland Chang, Gautam Dantas
NATURE CHEMICAL BIOLOGY
(2015)
Article
Multidisciplinary Sciences
Ming Gao, Trung T. Nguyen, Mark A. Suckow, William R. Wolter, Major Gooyit, Shahriar Mobashery, Mayland Chang
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Article
Microbiology
Joon Lee, Woo Yang, Andrew Hostetler, Nathan Schultz, Mark A. Suckow, Kay L. Stewart, Daniel D. Kim, Hyung Soo Kim
Article
Chemistry, Medicinal
Renee Bouley, Derong Ding, Zhihong Peng, Maria Bastian, Elena Lastochkin, Wei Song, Mark A. Suckow, Valerie A. Schroeder, William R. Wolter, Shahriar Mobashery, Mayland Chang
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Oncology
Jonathan D. Ashley, Charissa J. Quinlan, Valerie A. Schroeder, Mark A. Suckow, Vincenzo J. Pizzuti, Tanyel Kiziltepe, Basar Bilgicer
MOLECULAR CANCER THERAPEUTICS
(2016)
Article
Biochemistry & Molecular Biology
Major Gooyit, Zhihong Peng, William R. Wolter, Hualiang Pi, Derong Ding, Dusan Hesek, Mijoon Lee, Bill Boggess, Matthew M. Champion, Mark A. Suckow, Shahriar Mobashery, Mayland Chang
ACS CHEMICAL BIOLOGY
(2014)
Article
Biochemical Research Methods
Adam J. Plaunt, Kara M. Harmatys, William R. Wolter, Mark A. Suckow, Bradley D. Smith
BIOCONJUGATE CHEMISTRY
(2014)
Article
Chemistry, Multidisciplinary
Jonathan D. Ashley, Jared F. Stefanick, Valerie A. Schroeder, Mark A. Suckow, Nathan J. Alves, Rikio Suzuki, Shohei Kikuchi, Teru Hideshima, Kenneth C. Anderson, Tanyel Kiziltepe, Basar Bilgicer
JOURNAL OF CONTROLLED RELEASE
(2014)
Article
Chemistry, Medicinal
Jonathan D. Ashley, Jared F. Stefanick, Valerie A. Schroeder, Mark A. Suckow, Tanyel Kiziltepe, Basar Bilgicer
JOURNAL OF MEDICINAL CHEMISTRY
(2014)
Article
Multidisciplinary Sciences
Bridgette D. Semple, Linda J. Noble-Haeusslein, Major Gooyit, Kayleen G. Tercovich, Zhihong Peng, Trung T. Nguyen, Valerie A. Schroeder, Mark A. Suckow, Mayland Chang, Jacob Raber, Alpa Trivedi
Article
Veterinary Sciences
Kay L. Stewart, Mark A. Suckow
JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
(2016)