Article
Chemistry, Organic
Gang Yang, Lin Yao, Guojiang Mao, Guo-Jun Deng, Fuhong Xiao
Summary: We have reported a metal-free protocol for the synthesis of indenoquinolinones and 2-substituted quinolines via [4 + 2] cycloaddition reaction using readily available 2-aminobenzaldehydes and ketones as starting materials. Different quinoline derivatives can be selectively synthesized by changing the type of ketones. O-2 and dimethyl sulfoxide (DMSO) as co-oxidants play an important role in the synthesis of indenoquinolinones. This condensation/oxidation strategy involves the formation of C-N, C-C, and C-O bonds, with the advantages of high yields and a broad substrate range.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Gang Yang, Lin Yao, Guojiang Mao, Guo-Jun Deng, Fuhong Xiao
Summary: A metal-free protocol for the synthesis of indenoquinolinones and 2-substituted quinolines using readily available 2-aminobenzaldehydes and ketones has been reported. Different quinoline derivatives can be selectively synthesized by altering the type of ketones.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Qiang Ma, Ming Li, Zhuo Chen, Shao-Fei Ni, James S. Wright, Li-Rong Wen, Lin-Bao Zhang
Summary: An electrochemical protocol was developed for the synthesis of 2,3-disubstituted quinolines. The method is simple, mild, and does not require noble catalysts or external oxidants. It shows excellent regioselectivity and can tolerate various functional groups. The scaled-up experiment and follow-up procedures demonstrated the practicality of electrochemical synthesis.
Article
Chemistry, Medicinal
C. B. Pradeep Kumar, M. S. Raghu, B. S. Prathibha, M. K. Prashanth, G. Kanthimathi, K. Yogesh Kumar, L. Parashuram, Fahad A. Alharthi
Summary: A Ta2O5-anchored-piperidine-4-carboxylic acid (PPCA) nanoparticle was synthesized and used as an effective nanocatalyst for the synthesis of quinolin-2(1H)-one derivatives through C-O bond functionalization. The catalyst showed reusability for up to five cycles with no significant reduction in product yields, and the approach exhibited healthy reaction profiles, wide substrate scope, and excellent yields.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Organic
Qiongwen Kang, Mengdan Wang, Zongkang Wang, Lu Cheng, Yilin Zhu, Chengyu Wang, Yanzhong Li
Summary: A base-promoted selective C2-N1 ring-expansion reaction of indolones toward substituted quinolines under mild conditions has been developed, achieving the cleavage of one C-N bond and three C-C bonds, and the formation of one C-N and three C-C bonds in one step. This is the first example of a transition-metal free ring-expansion reaction of indolones via the selective insertion of alkynoates into the C2-N1 bond.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Biochemistry & Molecular Biology
Saira Naseem, Muhammad Ashraf, Samra Khan, Muhammad Rafiq, Muhammad Kashif, Jameel Rahman, Muhammad Khawar Rauf, Sobia Ahsan Halim, Jalal Uddin, Ajmal Khan, Ahmed Al-Harrasi, Zahid Shafiq
Summary: The study synthesized new hybrid pharmacophore N-substituted hydrazine-carbothioamides as potential urease inhibitors, with most derivatives demonstrating strong inhibitory potential. Molecular docking studies established the mode of interaction with urease, suggesting promising prospects for future modification and optimization.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Chemistry, Multidisciplinary
Johannes Grosskopf, Alexandra A. Heidecker, Thorsten Bach
Summary: Racemic 3-substituted oxindoles can be converted into enantiomerically pure or enriched material through photochemical deracemization process. Light energy compensates for the loss of entropy and enables predictable editing of the stereogenic center. The obtained oxindoles are valuable intermediates for further transformations with complete retention at the stereogenic center.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
S. K. Motahar, Atanu Bera, Debasis Banerjee
Summary: In this study, a general and efficient Ni-catalyzed protocol for sequential double de-hydrogenative cyclization was reported, which can convert 2-amino(nitro)-benzyl alcohols with primary alcohols to C-3-substituted quinolines, releasing water and dihydrogen as byproducts. The late stage functionalization of cholesterol derivatives, including chemo-selective transformations of citronellol, fatty acid derived oleyl alcohol, and long chain C-4-C-14 alkyl alcohols, was highlighted. Initial mechanistic studies, including deuterium-labelling experiments, were conducted to establish the de-hydrogenative cyclization.
Article
Biochemistry & Molecular Biology
Yuting Guo, Xia Peng, Yinchun Ji, Yitong Zhang, Jian Ding, Zhengsheng Zhan, Jing Ai, Wenhu Duan
Summary: The synthesized compound 8 was found to have potent antitumor activity by forming two canonical hydrogen bonds and a pi-pi stacking interaction with the ATP binding site of c-Met kinase domain.
MOLECULAR DIVERSITY
(2021)
Article
Biochemistry & Molecular Biology
Abdelfattah Hassan, Fawzy A. F. Mubarak, Ihsan A. A. Shehadi, Ahmed M. M. Mosallam, Hussain Temairk, Mohamed Badr, Aboubakr H. H. Abdelmonsef
Summary: The study focuses on the development of 3-substituted quinazoline-2,4(1H,3H)-dione derivatives as dual c-Met/VEGFR-2 TK inhibitors to overcome therapeutic resistance. Compound 2c, 4b, and 4e demonstrated strong inhibition of both c-Met and VEGFR-2 TK. In silico prediction of pharmacokinetic and physicochemical parameters using SwissADME suggested further optimization is required for these derivatives.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Derek R. Boyd, Narain D. Sharma, Pui L. Loke, Jonathan G. Carroll, Paul J. Stevenson, Patrick Hoering, Christopher C. R. Allen
Summary: The molecular docking studies of quinoline and 2-chloroquinoline substrates at the active site of toluene dioxygenase provided insights into novel edge-to-face interactions and explained the stereoselective cis-dihydroxylation of carbocyclic rings. The findings also supported the postulated cis-dihydroxylation of electron-deficient pyridyl rings, leading to the formation of hydroxyquinolines. The chemoenzymatic synthesis of enantiopure arene oxide and arene dioxide derivatives from 2-chloroquinoline cis-dihydrodiol metabolites demonstrated the potential implications for mammalian metabolism and carcinogenicity of quinoline.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Plant Sciences
Zhikun Yang, Jiahui Xu, Yumeng Bai, Zhao Wang, Liusheng Duan, Weiming Tan
Summary: The study found that compound S8 exhibited excellent promotion effects on plant growth, positively impacting the growth and development of Arabidopsis thaliana and rice. Molecular docking analysis showed that S8 had a tighter binding with the GID1 receptor, and its bioactivity displayed a clear negative association with the docking score values.
JOURNAL OF PLANT GROWTH REGULATION
(2022)
Article
Chemistry, Physical
Douglas J. Fansher, Richard Granger, Satinderpal Kaur, David R. J. Palmer
Summary: The chemoenzymatic synthesis of quinaldic acids under mild conditions using an aldolase resulted in up to 93% isolated yield. This reaction differs from aldol condensation catalyzed by NahE in vivo, resembling the heterocycle formation catalyzed by its homologue instead.
Article
Chemistry, Organic
Jin Wang, Haitao Liu, Yaohui Liu, Wanting Hao, Yingqi Yang, Yanan Sun, Xianxiu Xu
Summary: An efficient and environmentally friendly aerobic radical cascade reaction has been developed for the synthesis of a diverse range of 2-thio-substituted quinolines using o-vinylphenylisocyanides and thiols, without the need for additional catalysts or oxidants. Mechanistic investigations revealed that the reaction is initiated by a thiyl radical generated under aerobic conditions, which then undergoes radical annulation with a vinyl substituent.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Biochemistry & Molecular Biology
Zahra Abdulkarim Homoud, Muhammad Taha, Fazal Rahim, Naveed Iqbal, Muhammad Nawaz, Rai Khalid Farooq, Abdul Wadood, Munther Alomari, Imadul Islam, Shatha Algheribe, Ashfaq Ur Rehman, Khalid Mohammed Khan, Nizam Uddin
Summary: Acetylcholinesterase and butyrylcholinesterase are both valid therapeutic targets for ameliorating the cholinergic deficit in Alzheimer's disease. This study describes the synthesis of indole-based sulfonamide derivatives and their inhibitory activity against the enzymes. Compound 9 showed strong potential as an inhibitor.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)