Article
Chemistry, Organic
Xinchang Li, Huiru Yang, Zheyao Hu, Xin Jin, Wenyi Zhang, Xunxiang Guo
Summary: An environmentally benign protocol of visible-light-induced reaction has been developed for the effective synthesis of 4(3H)-quinazolinones from 2-benzylaminobenzamides. The reaction proceeds well under metal-free, photocatalyst-free and mediator-free conditions, providing the corresponding quinazolinones in good to high yields. Mechanism studies suggest that a radical pathway might be involved in the reaction.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ahmet Sevki Taskiran, Mustafa Ergul
Summary: Thiamine has a preventative effect on PTZ-induced seizures in rats and PTZ-induced neurotoxicity in SH-SY5Y neuroblastoma cells, reducing oxidative stress and apoptosis.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Review
Chemistry, Medicinal
Fabiana Plescia, Benedetta Maggio, Giuseppe Daidone, Demetrio Raffa
Summary: The quinazolinone nucleus is an important scaffold for obtaining biologically active molecules. Fused heterocycles from natural or synthetic sources are associated with a wide range of biological activities. This review focuses on 4-(3H)-quinazolinones N-3 substituted with a five-membered heterocycle containing nitrogen, sulfur, and oxygen atoms in various combinations.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Gamze Bayrak, Ismet Burcu Turkyilmaz, Refiye Yanardag
Summary: The study aimed to investigate the protective role of Vit U against PTZ-induced brain damage. The results showed that Vit U can alleviate oxidative stress caused by PTZ and protect brain tissue.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2022)
Article
Environmental Sciences
Canan Akunal Turel, Oruc Yunusoglu
Summary: The aim of this study was to investigate the protective effects of triterpene oleanolic acid on mice brain tissue with PTZ-induced epileptic seizures. PTZ injection caused significant seizures, but oleanolic acid treatment prolonged seizure onset latency and duration, and decreased seizure scores. Oleanolic acid also increased antioxidant enzyme activity and levels in the brain. These findings suggest that oleanolic acid may have anticonvulsant potential and protect against oxidative stress and cognitive disturbances in PTZ-induced seizures.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Marcia Perez-Fehrmann, Victor Kesternich, Arturo Puelles, Victor Quezada, Fernanda Salazar, Philippe Christen, Jonathan Castillo, Juan Guillermo Carcamo, Alejandro Castro-Alvarez, Ronald Nelson
Summary: A novel series of 6-iodo-2-methylquinazolin-4-(3H)-one derivatives were synthesized and evaluated for their cytotoxic activity. Several compounds exhibited remarkable cytotoxic activity against various cancer cell lines. Molecular docking and 3D-QSAR analysis correlated the activity with the interaction between the compounds and dihydrofolate reductase (DHFR).
Article
Endocrinology & Metabolism
Fatemeh Sadat Heydari, Mahmoud Gorji Valokola, Soghra Mehri, Khalil Abnous, Ali Roohbakhsh
Summary: This study investigated the role of TRPA1 in the treatment of epilepsy and found that the TRPA1 antagonist HC030031 can reduce the severity of seizures and prevent the upregulation of TRPA1 levels after seizure induction.
METABOLIC BRAIN DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Mateusz Pierog, Katarzyna Socala, Elzbieta Wyska, Ewa Poleszak, Piotr Wlaz
Summary: Ellagic acid, a natural dietary polyphenol, has beneficial effects including anti-inflammatory and antioxidant properties. Studies suggest that it may modulate seizure activity and increase seizure threshold in animal models, showing promising potential for anticonvulsant activity.
Article
Clinical Neurology
Hatice Aygun, Ali Tugrul Akin, Nildem Kizilaslan, Orhan Sumbul, Derya Karabulut
Summary: Probiotic supplementation may alleviate seizure severity and exert neuroprotective effects by reducing neuroinflammation and oxidative stress and altering the expression of neurotrophins in epileptogenic brains.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Arife Erdogan, Mumin Alper Erdogan, Ozum Atasoy, Oytun Erbas
Summary: The study found that Otilonium bromide significantly reduced seizure activity in rats, possibly through blocking T-type calcium channels. Further investigation into the clinical role of OB and other TTCC inhibitors as potential anti-seizure drugs is warranted.
NEUROCHEMICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Arife Erdogan, Mumin Alper Erdogan, Serkan Gurgul, Oytun Erbas
Summary: Epilepsy is a common disease that does not respond to currently available medications for many patients. Studies have shown that oxidative stress and inflammation may contribute to the development and progression of epilepsy. This research aimed to evaluate the effects of the nonsteroidal anti-inflammatory drug diclofenac sodium on seizure activity and oxidative stress and inflammatory biomarkers in a rat model of epilepsy. The results showed that diclofenac sodium effectively reduced seizure activity and levels of oxidative stress and inflammatory markers.
NEUROCHEMICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Sina Jourian, Mohammad Rahimi, Mohammad Amin Manavi, Mohammad-Taha Pahlevan-Fallahy, Razieh Mohammad Jafari, Ali Amini, Ahmad Reza Dehpour
Summary: This study found that ivermectin has an anticonvulsant effect on clonic seizure threshold. Furthermore, the anticonvulsant effect of ivermectin may be mediated through the interaction of the opioidergic system and the nitric oxide pathway.
NEUROCHEMICAL RESEARCH
(2023)
Article
Chemistry, Organic
Zhi Jiang, Dan-Dan Zhao, Yu-Tao Hu, Yong Rao, Shi-Yao Guo, Yao-Hao Xu, Qingjiang Li, Zhi-Shu Huang
Summary: A palladium-mediated amination method was developed for the direct modification of indolyl-4(3H)-quinazolinones, allowing the synthesis of derivatives with amino groups at all positions with good functional group tolerance. The antitumor activity of these products was also evaluated.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Behavioral Sciences
Julia Canzian, Francini Franscescon, Talise E. Mueller, Flavia Stefanello, Thiele P. Souza, Luiz Rosa, Denis B. Rosemberg
Summary: This study investigated the impact of stress on epileptic seizures in zebrafish, finding that previous exposure to intense acute stressors can increase seizure intensity and susceptibility. Additionally, heightened anxiety was found to make fish more prone to seizures.
EPILEPSY & BEHAVIOR
(2021)
Article
Chemistry, Multidisciplinary
Harrison M. Snodgrass, Dibyendu Mondal, Jared C. Lewis
Summary: In this study, a variant of the flavin-dependent halogenase RebH was engineered to catalyze site- and atroposelective halogenation reactions of 3-aryl-4(3H)-quinazolinones. The directed evolution process used a combination of mutagenesis, substrate walking, and screening methods to improve the conversion and selectivity of the enzyme. The resulting variant showed high activity and selectivity on multiple substrates, and computational modeling was used to understand the effects of key mutations on substrate binding. This study demonstrates the potential of flavin-dependent halogenases for atroposelective catalysis and highlights the versatility of RebH in accepting structurally diverse substrates for enantioselective synthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
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)