Article
Biochemistry & Molecular Biology
Qingfei Meng, Xue Ren, Rui Wang, Yu Han, Xiufen Li, Qin Zhang, Zhenpeng Li, Yuexing Wang, Longjiang Huang, Haibo Yu
Summary: A series of 3(1,2,3,6-tetrahydropyridine)-7-azaindole derivatives were synthesized and evaluated for their anticonvulsant activities and neurotoxicity. Compounds 4i, 4p, and 5k showed significant anticonvulsant activities in the PTZ-induced epilepsy model, but not in the MES model. These compounds also exhibited lower neurotoxicity. The presence of a N-atom at the 7-position of the 7-azaindole and a double-bond in the 1,2,3,6-tetrahydropyridine skeleton were found to be essential for the antiepileptic activities.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
M. S. Raghu, H. A. Swarup, B. S. Prathibha, K. Yogesh Kumar, C. B. Pradeep Kumar, Fahad A. Alharti, M. K. Prashanth, Byong-Hun Jeon
Summary: A series of 5,6-difluoro-1H-benzo[d]imidazole derivatives were designed and synthesized. These compounds showed promising anticonvulsant activity in mice, with compound 4d and 4e demonstrating 100% protection. In addition, these compounds were found to influence the GABA system by increasing GABA concentration in rat brains and exhibited high affinity for the GABAA receptor.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Plant Sciences
Reza Zadali, Mohsen Baghery, Mehdi Abbasi, Niksa Yavari, Mansour Miran, Samad Nejad Ebrahimi
Summary: This review examined the anticonvulsant activity of Iranian medicinal plants and used computational medicinal chemistry approaches to evaluate them. The results showed that the family Apiaceae was the most abundant in terms of antiepileptic application. Through a combination of experimental data, molecular docking, and physicochemical properties analysis, several plant compounds were identified to have anticonvulsant activity.
SOUTH AFRICAN JOURNAL OF BOTANY
(2022)
Review
Chemistry, Medicinal
Monika Stefaniak, Beata Olszewska
Summary: Benzoxazepines are a diverse group of organic compounds widely discussed in the literature, known for their various biological and pharmacological properties. Among them, 1,5-benzoxazepine derivatives play a significant role in organic synthesis and exhibit interesting characteristics in biological and pharmacological aspects.
ARCHIV DER PHARMAZIE
(2021)
Article
Chemistry, Multidisciplinary
Esraa M. Othman, Eman A. Fayed, Ebtehal M. Husseiny, Hamada S. Abulkhair
Summary: A new set of 1,2,3-triazoles was designed and synthesized to evaluate their potential as anticancer drugs. Three compounds showed mild to moderate growth inhibition activity against lung, renal, and prostate cancerous cells.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Organic
Yujia Sun, Ziwei Wang, Yan Wang, Tongxiu Xu, Keqing Tian, Ping Zhang
Summary: Four kinds of 1,5-benzothiazepines with triazole moiety were designed and synthesized, with isomerization of triazole occurring during the conversion to target compounds. Two new compounds were isolated, showing potential for development of antifungal drugs due to their inhibitory effects on fungi, including C. neoformans.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Gniewomir Latacz, Kinga Salat, Anna Furgala-Wojas, Adrian Martyniak, Agnieszka Olejarz-Maciej, Ewelina Honkisz-Orzechowska, Ewa Szymanska
Summary: Compound 1 showed significant antioxidant and neuroprotective activities, and demonstrated anticonvulsant potential in vivo. It may be a potential candidate for drug development.
Article
Neurosciences
Nilton Akio Muto, Moises Hamoy, Chryslen Brenda da Silva Ferreira, Akira Otake Hamoy, David Cristian Rodrigues Lucas, Vanessa Joia de Mello, Herve Rogez
Summary: This study demonstrated the anticonvulsant protective properties of Euterpe oleracea stone extract (EEOS) through EEG profiling in induced convulsing rats. The mechanism of action of EEOS is similar to diazepam (DZP) and involves the benzodiazepine (BDZ) subunit of the GABAA receptor.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Neurosciences
Eman A. A. Alraddadi, Abdulrahman M. M. Khojah, Faisal F. F. Alamri, Husun K. K. Kecheck, Wid F. F. Altaf, Yousef Khouqeer
Summary: Epilepsy is a common neurological disorder with a significant social and public health burden. Current therapies are ineffective for many patients, highlighting the need for novel treatment targets. Impaired brain energy metabolism and mitochondrial dysfunction are emerging as important factors in epilepsy development. Creatine, an organic compound involved in energy metabolism, shows promise as a potential treatment for neurological disorders with mitochondrial dysfunction.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Jun Wu, Zhipeng Hou, Yan Wang, Liping Chen, Chengxi Lian, Qingfei Meng, Chaoying Zhang, Xiufen Li, Longjiang Huang, Haibo Yu
Summary: A series of 7-alkoxy -[1,2,4] triazolo [1, 5-a] pyrimidine derivatives were synthesized and found to exhibit significant anti-seizure effects. The compounds mainly exerted their anticonvulsant activity by allosteric potentiation of GABA(A) receptors. Compound 10c, with potent activity, showed sensitivity to different subunit configurations of GABA(A) receptors and acted on distinct sites from benzodiazepines and barbiturates. These structural compounds may serve as a foundation for designing novel antiepileptic molecules.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ahmed A. A. Al Otaibi, Sinad L. L. Alshammari, Abdulmohsen Khalaf Dhahi Alsukaibi, Azfar Jamal, Saravanan Rajendrasozhan, Khalaf M. M. Alenezi, Afzal Hussain, Imran Khan, Md. Mushtaque, Ashanul Haque
Summary: Four new hybrid compounds (H1-H4) containing pyrazole (S1 and S2) and chalcone (P1 and P2) fragments were synthesized and characterized. The compounds were tested for their ability to inhibit the proliferation of human lung (A549) and colon (Caco-2) cancer cell lines, as well as their toxicity against normal cells. In silico studies were conducted to predict the binding modes, protein stability, drug-likeness, and toxicity of the compounds. The results showed dose-dependent cell-specific cytotoxicity and favorable binding affinity, drug-likeness properties, and low toxicity profiles.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
C. B. Pradeep Kumar, M. S. Raghu, K. N. N. Prasad, S. Chandrasekhar, B. K. Jayanna, Fahad A. Alharthi, M. K. Prashanth, K. Yogesh Kumar
Summary: Compounds 3g and 3h exhibited strong anti-tuberculosis activity with good affinity towards the target protein, making them potential lead compounds for the treatment of multi-drug resistant tuberculosis. Studies also indicated enhanced DNA binding properties of compound 3g compared to 3h, with promising K-b values. Density functional theory was utilized to obtain ground state geometries and energy calculations for further insight into the compounds' mechanism of action.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Sara Meirinho, Marcio Rodrigues, Adriana O. Santos, Amilcar Falcao, Gilberto Alves
Summary: The intranasal administration of Perampanel (PER) through the olfactory pathway showed improved brain distribution and demonstrated anticonvulsant and anxiolytic effects in mice, indicating a potential alternative to oral treatment for epilepsy and anxiety. However, it also caused some neuromotor impairment, which was improved with repeated administrations. The study supports the design of clinical trials to evaluate the efficacy of intranasal PER delivery in treating neurological-related conditions.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Biology
Rian W. Manville, Derk Hogenkamp, Geoffrey W. W. Abbott
Summary: Chemical and electrophysiological studies have identified carnosic acid, a constituent of rosemary extract, as a highly effective activator of neuronal KCNQ channels with unique selectivity for heteromers. Rosemary extract has been used medicinally for neurological disorders for thousands of years. Carnosic acid specifically activates KCNQ3/5 channels and has minimal effects on KCNQ2/3 or other KCNQ subunits. The molecular basis of carnosic acid's efficacy and selectivity lies in its interaction with an arginine residue in the S4-5 linker of KCNQ3.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biology
Jose Melesio Cristobal-Luna, Maria Angelica Mojica-Villegas, Sergio Enrique Meza-Toledo, Yuliana Garcia-Martinez, Angelica Perez-Juarez, German Chamorro-Cevallos
Summary: The study found that antiepileptic drugs have severe effects on embryonic development during pregnancy, causing various abnormalities. DL-4-hydroxy-4-phenylhexanamide (DL-HEPB), a phenyl alcohol amide compound with different structure from known anticonvulsants, showed good anticonvulsant effects in previous studies. The experiment demonstrated that DL-HEPB has lower developmental toxicity and could be a potential starting point for the design of new highly effective anticonvulsant drugs.
Review
Pharmacology & Pharmacy
G. G. Laxman Prabhu, Hiren Prajapati, Alok Chaturvedi, Nilanj Dave, Amit B. Jain
DRUGS & THERAPY PERSPECTIVES
(2019)
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)