Article
Chemistry, Medicinal
Ying-Jie Cui, Yi Zhou, Xi-wu Zhang, Bao-kai Dou, Chen-Chen Ma, Jing Zhang
Summary: By modifying the structure of indazole derivatives, a highly potent compound 8l with anticancer activity was obtained. This compound inhibits cell growth and migration by affecting cell cycle progression and apoptosis, and shows significant inhibition of tumor growth in vivo.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ling Luo, Yuqin Ou, Qi Zhang, Xiuhai Gan
Summary: Plant-parasitic nematodes pose a serious threat to crops, causing significant financial losses due to control difficulties. Tioxazafen, a novel nematicide, shows good prevention effects against various nematodes. In this study, 48 derivatives of 1,2,4-oxadiazole were synthesized and evaluated for their nematocidal activities. Most of the derivatives exhibited remarkable nematocidal activities against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus dipsaci. Compound A1 showed excellent nematocidal activity against B. xylophilus, outperforming other commercial nematicides. Transcriptome and enzyme activity analyses suggested that the nematocidal activity of compound A1 was mainly attributed to its effect on the acetylcholine receptor of B. xylophilus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Vishal Unadkat, Shishir Rohit, Paranjay Parikh, Vinod Sanna, Sanjay Singh
Summary: A molecular dynamics-based sampling of EGFR-TK was conducted for molecular docking of 1,2,4-oxadiazole derivatives, resulting in identification of compounds with better binding to EGFR in silico. Physicochemical properties analysis showed favorable characteristics and cytotoxicity against overexpressing EGFR cell lines, with 6a and 6b displaying the best IC50 values, indicating potential for further drug development.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Daniel L. Priebbenow, Mitch Mathiew, Da-Hua Shi, Jitendra R. Harjani, Julia G. Beveridge, Marina Chavchich, Michael D. Edstein, Sandra Duffy, Vicky M. Avery, Robert T. Jacobs, Stephen Brand, David M. Shackleford, Wen Wang, Longjin Zhong, Given Lee, Erin Tay, Helena Barker, Elly Crighton, Karen L. White, Susan A. Charman, Amanda De Paoli, Darren J. Creek, Jonathan B. Baell
Summary: A series of novel 3,3'-disubstituted-5,5'-bi(1,2,4-triazine) compounds with potent in vitro activity against Plasmodium falciparum parasites were recently discovered. The new structure-activity relationship investigation led to the identification of second-generation highly potent antimalarial bis-triazines, with improved in vitro metabolic stability and a fast-killing profile. This new class of orally available antimalarial compounds is of considerable interest.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Agnieszka Dreas, Katarzyna Kucwaj-Brysz, Karolina Pyziak, Urszula Kulesza, Ewelina Wincza, Charles-Henry Fabritius, Kinga Michalik, Ewelina Gabor-Worwa, Aniela Golas, Mariusz Milik, Magdalena Masiejczyk, Eliza Majewska, Kazimiera Pysniak, Urszula Wojcik-Trechcinska, Zuzanna Sandowska-Markiewicz, Krzysztof Brzozka, Jerzy Ostrowski, Tomasz Rzymski, Michal Mikula
Summary: The study suggests that inhibition of the MNKs/eIF4E pathway can potentially treat cancer and inflammatory diseases. Compounds 24 and 26, selective and metabolically stable MNK1/2 inhibitors, effectively reduce the phosphorylation levels of eIF4E in pathological conditions, leading to improved survival rates and reduced proinflammatory cytokine levels in mice models.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Mariia Yu. Rybak, Anatoliy O. Balanda, Anna P. Yatsyshyna, Igor. M. Kotey, Sergiy A. Starosyla, Volodymyr G. Bdzhola, Lubov L. Lukash, Sergiy M. Yarmoluk, Michael A. Tukalo, Galyna P. Volynets
Summary: This study identified potential antibacterial compounds targeting resistant strains of M. tuberculosis, although further optimization is needed to develop non-toxic antituberculosis agents with a novel mechanism of action.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Amal Kamal Abdel-Aziz, Eman M. E. Dokla, Khaled A. M. Abouzid, Saverio Minucci
Summary: This study discovered a novel endoplasmic reticulum (ER) inducer, EMD37, which exhibited potent anticancer activity against NCI-60 cancer cell lines. Genome-wide transcriptome profiling and drug signature mining revealed that EMD37 promoted ER stress and unfolded protein response (UPR) mechanisms. Additionally, EMD37 inhibited mTOR signaling and induced G2/M cell cycle arrest and apoptosis in human cancer cells.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Zhiyuan Cheng, Yijie Wang, Yao Zhang, Chan Zhang, Mengru Wang, Wei Wang, Jiacheng He, Yang Wang, Hankun Zhang, Qiansen Zhang, Chunyong Ding, Deyan Wu, Linlin Yang, Mingyao Liu, Weiqiang Lu
Summary: In recent years, small-molecule drugs have become essential in tumor immunotherapy. The study identified compound 1 as an EP4 antagonist hit, which showed promising antitumor immune response by blocking PGE2/EP4 signaling. Further exploration led to the discovery of compound 14, which displayed high EP4 antagonistic activity, selectivity, and favorable drug-like profiles. When administered orally, compound 14 significantly inhibited tumor growth by enhancing cytotoxic CD8+ T cell-mediated antitumor immunity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Kan Yang, Keyi Nong, Fei Xu, Yu Chen, Jinying Yu, Lizhi Lin, Xiao Hu, Youzhi Wang, Ting Li, Jibin Dong, Jinxin Wang
Summary: In this study, a series of benzene-heterocyclic-based ASM inhibitors were designed, synthesized, and screened, and some compounds showed favorable inhibitory activity against recombinant human ASM. Compound 4i exhibited good pharmacokinetic properties and in vivo inhibitory activity against ASM, reducing the level of ceramide in mice plasma and liver. Moreover, 4i was found to decrease lipid plaques, plasma ceramide concentration, and Ox-LDL levels, and to regulate cell inflammation induced by LPS and Ox-LDL by modulating the levels of ceramide and sphingomyelin. Overall, this study demonstrates the potential of ASM as an effective target for treating atherosclerosis.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Agricultural Engineering
Yuge Hu, Yanqing Gao, Yujia Wang, Wenguang Zhang, Hanru Liu, Xingjia Zhang, Zhiqing Ma, Xili Liu, Peng Lei
Summary: In this study, a series of compounds were designed and synthesized, showing satisfactory fungicidal activity. The structure-activity relationship analysis revealed that the tetrahydro(iso)quinoline substitution was crucial for enhancing the activity. The biochemistry and physiology response of the target compounds on the phytopathogen were investigated, leading to profound effects on the fungus. Theoretical calculations were also performed to assess the molecular descriptors of representative compounds.
INDUSTRIAL CROPS AND PRODUCTS
(2022)
Article
Plant Sciences
Enjing Cui, Shihu Qian, Jiaming Li, Xueyang Jiang, Hongwei Wang, Shuaishuai Du, Le Du
Summary: In this study, 26 derivatives of Coixol were designed and synthesized to discover new anti-inflammatory agents. The derivatives containing furan or nitrofuran moieties exhibited stronger anti-inflammatory activity than Coixol and celecoxib, as evidenced by the reduced expression of iNOS, TNF-α, IL-6, and IL-1β. Mechanistic investigations revealed that the inhibition of the NF-κB signaling pathway contributed to the anti-inflammatory effects of 9c and 9j. In vivo studies confirmed their anti-inflammatory activity in a xylene-induced mice auricles edema model.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Organic
Jesse Lingam, Bijaya Ketan Sahoo, Bala Divya Mallavarapu, Reddymasu Sreenivasulu
Summary: A series of new compounds were designed and synthesized, and their anticancer activity was evaluated. One of the compounds showed significant activity and molecular docking studies suggested its potential binding to tubulin. These results provide important information for the development of anticancer therapies.
SYNTHETIC COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Bongki Ko, Yongsoo Jang, Min Ha Kim, Thai Thi Lam, Hye Kyung Seo, Pyeonghwa Jeong, Munkyung Choi, Keon Wook Kang, So-Deok Lee, Jin-Hee Park, Myungjin Kim, Sun-Young Han, Yong-Chul Kim
Summary: This study developed novel inhibitors targeting mutant FLT3 kinases through chemical moieties optimization. The optimized compound 22f exhibited potent inhibitory activities against FLT3 and FLT3/D835Y, as well as strong antiproliferative activity against AML cell line MV4-11 cells. It also showed single-digit nanomolar inhibitory values in mutant FLT kinase expressed cell lines.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Na Li, Qi Guan, Yilang Hong, Bowen Zhang, Mi Li, Xuewen Li, Bo Li, Weige Zhang, Lan Wu
Summary: Tubulin/colchicine-binding site inhibitors co-crystal structures are important for finding new small molecules for cancer therapy. A series of 6-aryl-2-(3,4,5-trimethoxyphenyl)thiazole[3,2-b][1,2,4]triazoles were designed as tubulin polymerization inhibitors targeting the colchicine domain. Compound 7w showed significant potency against SGC-7901 cancer cells (IC50 = 0.21 mu M) and lower cytotoxicity than colchicine in normal cells (HUVEC). Mechanistic studies revealed that 7w induced cancer cell apoptosis by inhibiting tubulin polymerization and triggering G2/M arrest. In a 4T1 xenograft mice model, 7w effectively inhibited tumor growth without causing weight loss, indicating promising potential for further development with its unique binding mode at the colchicine-binding site.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Tao Pan, Yanrong Dan, Dafeng Guo, Junhao Jiang, Dongzhi Ran, Lin Zhang, Binghua Tian, Jianyong Yuan, Yu Yu, Zongjie Gan
Summary: The newly designed compound 10f showed potent inhibitory activity against both ALK and HDAC, effective against resistant mutants and exhibiting significant anti-proliferative effects on cancer cells at low concentrations.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Maria R. Abbattista, Stephen M. F. Jamieson, Yongchuan Gu, Jennifer E. Nickel, Susan M. Pullen, Adam V. Patterson, William R. Wilson, Christopher P. Guise
CANCER BIOLOGY & THERAPY
(2015)
Article
Oncology
Francis W. Hunter, Richard J. Young, Zvi Shalev, Ravi N. Vellanki, Jingli Wang, Yongchuan Gu, Naveen Joshi, Sreevalsan Sreebhavan, Ilan Weinreb, David P. Goldstein, Jason Moffat, Troy Ketela, Kevin R. Brown, Marianne Koritzinsky, Benjamin Solomon, Danny Rischin, William R. Wilson, Bradly G. Wouters
Article
Oncology
Ji Cao, Yijie Wang, Rong Dong, Guanyu Lin, Ning Zhang, Jing Wang, Nengming Lin, Yongchuan Gu, Ling Ding, Meidan Ying, Qiaojun He, Bo Yang
Article
Hematology
Marina Konopleva, Peter F. Thall, Cecilia Arana Yi, Gautam Borthakur, Andrew Coveler, Carlos Bueso-Ramos, Juliana Benito, Sergej Konoplev, Yongchuan Gu, Farhad Ravandi, Elias Jabbour, Stefan Faderl, Deborah Thomas, Jorge Cortes, Tapan Kadia, Steven Kornblau, Naval Daver, Naveen Pemmaraju, Hoang Q. Nguyen, Jennie Feliu, Hongbo Lu, Caimiao Wei, William R. Wilson, Teresa J. Melink, John C. Gutheil, Michael Andreeff, Elihu H. Estey, Hagop Kantarjian
Article
Hematology
Marina Konopleva, Peter F. Thall, Cecilia Arana Yi, Gautam Borthakur, Andrew Coveler, Carlos Bueso-Ramos, Juliana Benito, Sergej Konoplev, Yongchuan Gu, Farhad Ravandi, Elias Jabbour, Stefan Faderl, Deborah Thomas, Jorge Cortes, Tapan Kadia, Steven Kornblau, Naval Daver, Naveen Pemmaraju, Hoang Q. Nguyen, Jennie Feliu, Hongbo Lu, Caimiao Wei, William R. Wilson, Teresa J. Melink, John C. Gutheil, Michael Andreeff, Elihu H. Estey, Hagop Kantarjian
Article
Pharmacology & Pharmacy
Yongchuan Gu, Tony T. -A. Chang, Jingli Wang, Jagdish K. Jaiswal, David Edwards, Noel J. Downes, H. D. Sarath Liyanage, Courtney R. H. Lynch, Frederik B. Pruijn, Anthony J. R. Hickey, Michael P. Hay, William R. Wilson, Kevin O. Hicks
FRONTIERS IN PHARMACOLOGY
(2017)
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Pharmacology & Pharmacy
Francis W. Hunter, Jagdish K. Jaiswal, Daniel G. Hurley, H. D. Sarath Liyanage, Sarah P. McManaway, Yongchuan Gu, Susan Richter, Jingli Wang, Moana Tercel, Cristin G. Print, William R. Wilson, Frederik B. Pruijn
BIOCHEMICAL PHARMACOLOGY
(2014)
Article
Pharmacology & Pharmacy
Stephen M. F. Jamieson, Yongchuan Gu, Donya Moradi Manesh, Jad El-Hoss, Duohui Jing, Karen L. MacKenzie, Christopher P. Guise, Annika Foehrenbacher, Susan M. Pullen, Juliana Benito, Jeffrey B. Smaill, Adam V. Patterson, Medhanie A. Mulaw, Marina Konopleva, Stefan K. Bohlander, Richard B. Lock, William R. Wilson
BIOCHEMICAL PHARMACOLOGY
(2014)
Article
Biochemistry & Molecular Biology
Muriel Bonnet, Cho Rong Hong, Yongchuan Gu, Robert F. Anderson, William R. Wilson, Frederik B. Pruijn, Jingli Wang, Kevin O. Hicks, Michael P. Hay
BIOORGANIC & MEDICINAL CHEMISTRY
(2014)
Article
Oncology
Mark J. McKeage, Michael B. Jameson, Ramesh K. Ramanathan, Joseph Rajendran, Yongchuan Gu, William R. Wilson, Teresa J. Melink, N. Simon Tchekmedyian
Article
Pharmacology & Pharmacy
Guanyu Lin, Renhua Gai, Zibo Chen, Yijie Wang, Sida Liao, Rong Dong, Hong Zhu, Yongchuan Gu, Qiaojun He, Bo Yang
EUROPEAN JOURNAL OF PHARMACOLOGY
(2014)
Article
Biochemistry & Molecular Biology
Jiechuang Su, Yongchuan Gu, Frederik B. Pruijn, Jeff B. Smaill, Adam V. Patterson, Christopher P. Guise, William R. Wilson
JOURNAL OF BIOLOGICAL CHEMISTRY
(2013)
Article
Chemistry, Medicinal
Yongchuan Gu, Jagdish K. Jaiswal, Jingli Wang, Kevin O. Hicks, Michael P. Hay, William R. Wilson
JOURNAL OF PHARMACEUTICAL SCIENCES
(2014)
Article
Pharmacology & Pharmacy
Way Wua Wong, Rosanna K. Jackson, Lydia P. Liew, Benjamin D. Dickson, Gary J. Cheng, Barbara Lipert, Yongchuan Gu, Francis W. Hunter, William R. Wilson, Michael P. Hay
BIOCHEMICAL PHARMACOLOGY
(2019)