Article
Chemistry, Organic
Dmitry I. Bugaenko, Alexey A. Volkov, Alexander V. Karchava
Summary: Most existing methods for alkyl arylthioether synthesis rely on using mercaptans as starting materials, which has practical limitations. A thiol-free method for the synthesis of these valuable compounds is proposed, utilizing reactions between diaryliodonium salts and xanthate salts, derived from corresponding alcohols and CS(2), under the developed conditions. The protocol showcases high functional group tolerance and can be used for late-stage C-H functionalization and introduction of a CD3S group.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Tugce G. Erbay, Daniel P. Dempe, Bhaskar Godugu, Peng Liu, Kay M. Brummond
Summary: This study demonstrates that alpha-methylene-gamma-lactams can serve as tunable surrogates for highly reactive alpha-methylene-gamma-lactones, with the reactivity of the alpha-methylene modulated by the N substituent. Density functional theory calculations using the M06-2X functional with the SMD solvation model and methyl thiolate as a model nucleophile reliably predict the relative reactivities of the alpha-methylene-gamma-lactams. Quasiharmonic approximations further improve the agreement between experimental results and computational predictions.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Agriculture, Multidisciplinary
Liang-Kun Zhong, Xin-Peng Sun, Liang Han, Cheng-Xia Tan, Jian-Quan Weng, Tian-Ming Xu, Jian-Jun Shi, Xing-Hai Liu
Summary: This study focused on the design and synthesis of a series of novel insecticides. One compound, IA-8, showed excellent insecticidal activity against M. separate, comparable to the positive control fluralaner. Molecular docking results demonstrated that IA-8 and fluralaner have a similar binding mode to the GABA active site. This work provides a promising starting point for further optimization of insecticides.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Anthony Marchand, Lucia Bonati, Sailan Shui, Leo Scheller, Pablo Gainza, Steiphane Rosset, Sandrine Georgeon, Li Tang, Bruno E. Correia
Summary: Protein-based therapeutics, such as monoclonal antibodies and cytokines, are important treatments for various diseases, but their wide application is often limited by toxicities and adverse effects. In this study, researchers have designed and applied small-molecule-controlled switchable protein therapeutics by utilizing an OFF-switch system. By optimizing the affinity between B-cell lymphoma 2 protein and a designed protein partner, the addition of a competing drug can efficiently disrupt the protein function in vitro and lead to fast clearance in vivo. This study provides a proof-of-concept for the controllable design of protein-based therapeutics by introducing a drug-induced OFF-switch.
ACS CHEMICAL BIOLOGY
(2023)
Review
Chemistry, Medicinal
Tiandi Ding, Ying Zhi, Weilin Xie, Qingqiang Yao, Bo Liu
Summary: Sphingosine kinases are lipid kinases that phosphorylate sphingosine to sphingosine-1-phosphate, playing a role in regulating biological processes; targeting their signaling pathway is a potential treatment strategy for various pathophysiological conditions.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Lori D. Digal, Emily K. Kirkeby, Maxwell J. Austin, Andrew G. Roberts
Summary: Progress has been made in the design and synthesis of ambiphilic aryl thiol-iminium-based small molecules for organo-catalyzed thioacyl aminolysis. A novel tetrahydroisoquinoline-derived scaffold with both thiol and iminium functionalities has been synthesized and shown to promote the necessary reactions for organocatalyzed thioacyl aminolysis. Model studies have demonstrated the ability of this designed organocatalyst to deliver critical intermediates for the proposed process. Future improvements and directions towards cysteine-independent organocatalyzed native chemical ligation are discussed.
Article
Chemistry, Organic
Daniel P. Dempe, Chong-Lei Ji, Peng Liu, Kay M. Brummond
Summary: This study synthesized a series of N-aryl-substituted alpha-methylene-gamma-lactams within the framework of a bioactive guaianolide analog. The effects of the guaianolide structure on the electrophilic reactivity were investigated by reacting these compounds with glutathione and measuring rate constants. The trans-annulated compounds showed approximately a 10-fold increase in reactivity compared to the cis annulated compounds and the corresponding N-arylated 3-methylene-2-pyrrolidinones.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jianqing Zhang, Pengqin Chen, Yongli Duan, Hehua Xiong, Hongmin Li, Yao Zeng, Guang Liang, Qidong Tang, Di Wu
Summary: A series of novel compounds were synthesized and tested for their moderate to excellent activity against cancer cell lines in vitro. One of the compounds showed promising potential to be a candidate for the development of anti-tumor drugs, with better activity and apoptosis effect than the positive control. Further research on this compound included c-Met kinase activity and selectivity, concentration dependence, and molecular docking.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Thomas F. Durand-Reville, Alita A. Miller, John P. O'Donnell, Xiaoyun Wu, Mark A. Sylvester, Satenig Guler, Ramkumar Iyer, Adam B. Shapiro, Nicole M. Carter, Camilo Velez-Vega, Samir H. Moussa, Sarah M. McLeod, April Chen, Angela M. Tanudra, Jing Zhang, Janelle Comita-Prevoir, Jan A. Romero, Hoan Huynh, Andrew D. Ferguson, Peter S. Horanyi, Stephen J. Mayclin, Henry S. Heine, George L. Drusano, Jason E. Cummings, Richard A. Slayden, Ruben A. Tommasi
Summary: The study presents a rational design strategy for developing new antibiotics to combat infections caused by drug-resistant Gram-negative pathogens. The inhibitors are able to overcome multiple mechanisms of resistance and show potential clinical efficacy against superbugs.
Article
Chemistry, Physical
Haoyu S. Yu, Kalyan Modugula, Osamu Ichihara, Kimberly Kramschuster, Simon Keng, Robert Abel, Lingle Wang
Summary: Fragment linking is an important technique in optimizing the binding potency of fragment hits in drug discovery, but successful strategies are rare due to various confounding factors. The change in relative configurational entropy of the fragments in the protein binding pocket is found to be the dominant reason for the lack of expected gains in binding potency. This study provides insights that should facilitate the formulation of more successful fragment linking strategies in the future.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Biochemistry & Molecular Biology
Eslam M. H. Ali, Mohammed S. Abdel-Maksoud, Usama M. Ammar, Karim Mersal, Kyung Ho Yoo, Park Jooryeong, Chang-Hyun Oh
Summary: The study developed and synthesized a series of compounds with anticancer potential, demonstrating promising activity in various cancer types. Two compounds showed notable anti-cancer effects on Melanoma cancer cell lines.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
El Sayed H. El Ashry, Mohamed M. K. Farahat, Laila F. Awad, Mahmoud Balbaa, Hoda Yusef, Mohamed E. Badawy, Mohamed N. Abd Al Moaty
Summary: A series of 1,2,4-triazole Schiff's bases and their corresponding acyclo thioglycoside derivatives were synthesized and evaluated as inhibitors of alpha-glucosidase and alpha-amylase. The synthesized compounds exhibited excellent inhibitory activity against both enzymes, surpassing the standard drug acarbose. The most promising derivatives contained specific phenyl groups. Kinetic and molecular docking studies provided further insights into the inhibitory mechanism and binding interactions.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Agronomy
Li-Xia Zhao, Zhi-Xin Wang, Jian-Feng Peng, Yue-Li Zou, Yong-Zhuo Hui, Yong-Zheng Chen, Shuang Gao, Ying Fu, Fei Ye
Summary: The study focused on designing and synthesizing novel PPO inhibitor herbicides by linking a diphenylether pyridine bioisostere structure to substituted coumarins. A total of 21 compounds were synthesized and characterized, with compound IV-6 showing better herbicidal activity in greenhouse and field experiments compared to the commercial herbicide oxyfluorfen.
PEST MANAGEMENT SCIENCE
(2021)
Article
Polymer Science
Jinghua Tan, Junyi Shen, Jie Huang, Fengyun Xie, Xueyuan Liu, Chunbo Zhao, Huipeng Li, Yiwu Liu
Summary: A soluble intrinsically black polyimide with exceptional electrical and mechanical performances was designed and prepared. The introduction of a new chromophore into the polyimide molecular chain allowed absorption of the entire visible light spectrum. The resulting polyimide exhibited highly opaque and black color, with excellent solubility, mechanical and electrical performance.
Article
Multidisciplinary Sciences
Kohei Umedera, Atsushi Yoshimori, Juergen Bajorath, Hiroyuki Nakamura
Summary: New inhibitors of matrix metalloproteinase 1 (MMP-1) were predicted using the structure-activity relationship (SAR) transfer method based on analogues of kinesin-like protein 11 (KIF11) inhibitors. Synthesized compounds 5-7 showed high potency against MMP-1, with compound 6 having about 3.5 times higher inhibitory activity than compound 4. This increased activity may be attributed to a halogen bond interaction between the Cl substituent of compound 6 and residue ARG214 of MMP-1.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)