Review
Biochemistry & Molecular Biology
Martin Alexander Schick, Nicolas Schlegel
Summary: Phosphodiesterase 4 inhibitors play an important role in regulating physiological functions and treating diseases, but they also carry significant risks of serious side effects. This review aims to provide a comprehensive overview of the approaches and effects of phosphodiesterase 4 inhibition in different therapeutic applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Food Science & Technology
Zhiyun Peng, Guangcheng Wang, Qiao-Hui Zeng, Yufeng Li, Haiquan Liu, Jing Jing Wang, Yong Zhao
Summary: Tyrosinase is a copper-containing oxidation enzyme responsible for melanin production and plays a key role in browning, antibiotic resistance, pigment formation, etc. Synthetic tyrosinase inhibitors have great potential applications and have been widely reported in recent years.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2022)
Article
Chemistry, Medicinal
Mark E. Layton, Jeffrey C. Kern, Timothy J. Hartingh, William D. Shipe, Izzat Raheem, Monika Kandebo, Robert P. Hayes, Sarah Huszar, Donnie Eddins, Bennett Ma, Joy Fuerst, Gordon K. Wollenberg, Jing Li, Jeff Fritzen, Georgia B. McGaughey, Jason M. Uslaner, Sean M. Smith, Paul J. Coleman, Christopher D. Cox
Summary: PDE10A is an important regulator of striatal signaling. Inhibition of PDE10A may offer a new treatment option for schizophrenia. This study describes the discovery of an isomeric pyrimidine series that led to the development of compound 18 (MK-8189), which is currently in Phase 2b clinical development for schizophrenia.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Hoang Oanh Nguyen, Tiziana Schioppa, Laura Tiberio, Fabrizio Facchinetti, Gino Villetti, Maurizio Civelli, Annalisa Del Prete, Francesca Sozio, Carolina Gaudenzi, Mauro Passari, Ilaria Barbazza, Silvano Sozzani, Valentina Salvi, Daniela Bosisio
Summary: This article reports the research results of an oral PDE4 inhibitor called Tanimilast, which can modulate the pro-inflammatory potential and Th1-polarizing potential of SCV2-RNA-induced DCs. Tanimilast did not affect the expression of maturation markers and lymph node homing receptor in DCs, but skewed towards Th2 phenotype. Both Tanimilast and the reference drug β-methasone blocked the increase of MHC-I molecules in activated DCs and restrained the proliferation and activation of cytotoxic CD8(+) T cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Medicinal
Jing Zhang, Yang Yang, Xing-Kai Qian, Pei-Fang Song, Yi-Shu Zhao, Xiao-Qing Guan, Li-Wei Zou, Xiaoze Bao, Hong Wang
Summary: In this study, a novel compound P32 was designed and synthesized as a potent mixed-competitive inhibitor of pancreatic lipase (PL), displaying some selectivity over other known serine hydrolases. Molecular docking study revealed that the inhibitory activity of P32 towards PL could be attributed to specific interactions with the active site of PL.
Article
Biochemistry & Molecular Biology
Mengdie Gong, Mingyan Tu, Hongxia Sun, Lu Li, Lili Zhu, Honglin Li, Zhenjiang Zhao, Shiliang Li
Summary: This study presents three series of compounds designed and synthesized based on the structure of skepinone-L, a known MAPK14 inhibitor. Among the synthesized compounds, 13a and 13b displayed the best inhibitory activities against MAPK11. The structure-activity relationship (SAR) discussed in detail is constructive in optimizing MAPK11 inhibitors.
Article
Chemistry, Medicinal
Jiayuan Liu, Xianglei Zhang, Guofeng Chen, Qiang Shao, Yi Zou, Zhewen Li, Haixia Su, Minjun Li, Yechun Xu
Summary: This study discovered novel drug-like PDE4 inhibitors through high-throughput drug repurposing screening and elucidated their molecular mechanisms of action through crystal structure analysis. It also revealed that CVT-313 is a potent PDE5 inhibitor and led to the discovery of a new inhibitor with improved activity and selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Monika A. Lewandowska-Goch, Anna Kwiatkowska, Kevin Ly, Pauline Navals, Hugo Gagnon, Yves L. Dory, Adam Prahl, Robert Day, Teresa Lepek
Summary: The study aimed to improve the affinity of CF1 by altering its PS position. Results showed that substituting the PS position with small hydrophobic residues or a basic residue can enhance the activity of CF1.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Microbiology
Maria G. Nava, Felix Calderon, Elena Fernandez, Lluis Ballell, Paul Bamborough, Sumiti Vinayak
Summary: The intestinal parasite Cryptosporidium parvum is a major cause of diarrhea-associated morbidity and mortality in children, immunocompromised people, and young ruminant animals. With no effective drug available to treat cryptosporidiosis in humans and animals, there is an urgent need to identify anti-parasitic compounds and new targets for drug development.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Yue Zhang, Jiankun Song, Yuanzhang Zhou, Huijun Jia, Tianyu Zhou, Yingbo Sun, Qiong Gao, Yue Zhao, Yujie Pan, Zhaolin Sun, Peng Chu
Summary: Ubiquitin-specific protease 22 (USP22) plays a prominent role in tumor development and immune reprogramming, and has been proposed as a potential therapeutic target for cancer. Rottlerin and Morusin were discovered as selective and potent USP22 inhibitors, which can increase histone ubiquitination levels and reduce the expression of Sirt1 and PD-L1 proteins. These findings suggest that Rottlerin and Morusin may have potential as drugs for anticancer therapy.
BIOORGANIC CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Aleen Khoury, Jennette A. Sakoff, Jayne Gilbert, Kieran F. Scott, Shawan Karan, Christopher P. Gordon, Janice R. Aldrich-Wright
Summary: Platinum(IV) prodrugs showed outstanding activity against various cancer cell lines, with nanomolar activities observed. Cellular accumulation of the complexes was correlated with increased cytotoxicity. COX inhibition or lipophilicity did not solely determine the cytotoxicity of these prodrugs.
Article
Chemistry, Medicinal
Renjie Chen, Ramin Hassankhani, Yi Long, Sunita K. C. Basnet, Theodosia Teo, Yuchao Yang, Laychiluh Mekonnen, Mingfeng Yu, Shudong Wang
Summary: In this study, a series of N-pyridinylpyrimidin-2-amines were designed, synthesized, and evaluated, among which one compound was found to be the most potent inhibitor of CDKs 7 and 9 and the most effective anti-proliferative agent against multiple human cancer cell lines.
Article
Chemistry, Medicinal
Biao Xu, Zhi-Peng Wang, Qingwang Liu, Xiaohong Yang, Xuemin Li, Ding Huang, Yanfei Qiu, Kin Yip Tam, Shao-Lin Zhang, Yun He
Summary: This study reported a series of novel dichloroacetophenones as potent PDKs inhibitors, with compound 6u showing significant anti-proliferative effects on various cancer cells. In mouse models, 6u demonstrated potent antitumor activity without negative impact on body weight. The compound was also found to induce cancer cell apoptosis, arrest cell cycle progression, inhibit cell migration, and alter glucose metabolic pathways in cancer cells, showing potential as a modulator for reprogramming glycolysis in cancer cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Md Ashraf-Uz-Zaman, Xin Li, Yuan Yao, Chandra Bhushan Mishra, Bala Krishna Moku, Yongcheng Song
Summary: Dengue (DENV) and Zika (ZIKV) viruses are significant human pathogens, causing about 100 million symptomatic infections annually. These infections lead to a higher incidence of serious neurological diseases, such as microcephaly and Guillain-Barre syndrome. A study identified 2,3,6-trisubstituted quinazolinone compounds as novel inhibitors of ZIKV replication. Several analogues were synthesized and tested, and compounds 22, 27, and 47 showed potent activities against ZIKV and DENV with low cytotoxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Tanya Prasad, Aastha Mahapatra, Tripti Sharma, Chita R. Sahoo, Rabindra Nath Padhy
Summary: Cancer is a serious disease without a sustainable solution. The search for better cancer treatments has led to the development and study of new scaffolds, such as Dihydropyrimidinones (DHPMs), which are known for their versatile range of biological activities. This review summarizes the structure-activity relationship of DHPMs as potential anticancer agents, including their synthesis, mechanism of action, and the interlinked mechanisms leading to their anticancer activity.
ARCHIV DER PHARMAZIE
(2023)
