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Biochemistry & Molecular Biology
Mehmet Abdullah Alagoz, Jong Min Oh, Yaren Nur Zenni, Zeynep Ozdemir, Mohamed A. Abdelgawad, Ibrahim A. Naguib, Mohammed M. Ghoneim, Nicola Gambacorta, Orazio Nicolotti, Hoon Kim, Bijo Mathew
Summary: The study synthesized and evaluated 16 compounds, finding that TR2 and TR16 showed potent and highly selective inhibition against MAO-B, making them promising for managing multiple neurodegenerative diseases.
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Chemistry, Medicinal
Badr Jismy, Abdelkarim El Qami, Anja Pislar, Rok Frlan, Janko Kos, Stanislav Gobec, Damijan Knez, Mohamed Abarbri
Summary: Heterotricyclic compounds exhibit potential as MAO inhibitors, particularly showing selective inhibition towards human MAO-B isoform. These derivatives are non-cytotoxic to neuroblastoma cells and have demonstrated protective effects against 6-hydroxydopamine-induced cell death.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ahmed Elkamhawy, Hyeon Jeong Kim, Mohamed H. Elsherbeny, Sora Paik, Jong-Hyun Park, Lizaveta Gotina, Magda H. Abdellattif, Noha A. Gouda, Jungsook Cho, Kyeong Lee, Ae Nim Pae, Ki Duk Park, Eun Joo Roh
Summary: This study reported the design and synthesis of twenty-six new indole derivatives as potential MAO-B inhibitors, with compound 5 showing high inhibitory activity against hMAO-B and good selectivity index. The compound also demonstrated low cytotoxicity, promising neuroprotective effect, and high CNS bioavailability, making it a potent candidate for PD treatment.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sheunopa C. Mzezewa, Sylvester I. Omoruyi, Luke S. Zondagh, Sarel F. Malan, Okobi E. Ekpo, Jacques Joubert
Summary: The study synthesized and evaluated a series of 3,7-substituted coumarin derivatives for enzyme inhibitory activity and neuroprotective ability, with the compounds showing potential MAO-B inhibition activity and neuroprotective effects.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Magdalena Kondeva-Burdina, Javor Mitkov, Iva Valkova, Lily Peikova, Maya Georgieva, Alexander Zlatkov
Summary: The neurotoxic, neuroprotective, and MAO-B inhibitory effects of a series of N'-substituted 3-(1,3,7-trimethyl-xanthin-8-ylthio)propanehydrazides were evaluated. Compounds N'-(2,3-dimethoxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6k) and N'-(2-hydroxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6l) were identified as the most promising. QSTR analysis revealed that reduced lipophilicity and smaller dipole moments of the molecules contribute to lower neurotoxicity. These findings provide initial information for the further design of (xanthinyl-8-ylthio)propanhydrazides with potential hMAOB inhibitory effect and pronounced neuroprotection.
Article
Biochemistry & Molecular Biology
Amina Moutayakine, Carolina Marques, Oscar Lopez, Donatella Bagetta, Luisa Leitzbach, Stefanie Hagenow, Elisabete P. Carreiro, Holger Stark, Stefano Alcaro, Jose G. Fernandez-Bolanos, Anthony J. Burke
Summary: A new gem-dimethylchroman-4-ol family of compounds was developed in this study, showing good inhibition of equine serum butyrylcholinesterase (eqBuChE), making them suitable as inhibitors for BuChE.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ahmed Elkamhawy, Sora Paik, Jong-Hyun Park, Hyeon Jeong Kim, Ahmed H. E. Hassan, Kyeong Lee, Ki Duk Park, Eun Joo Roh
Summary: A series of safinamide-derived new analogs were studied, with some compounds showing potent inhibitory activities against hMAO-B. Compound 4bf exhibited excellent activity and selectivity, showing significant protective effects in a mouse model of PD.
BIOORGANIC CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Ashwani Kumar, Meenakshi Bhatia, Archana Kapoor, Parvin Kumar, Sunil Kumar, Sunil Kumar
Summary: Monoamine oxidase enzyme plays an essential role in brain function regulation, with its inhibitors showing potential in the treatment of neurological disorders. Reversible MAO inhibitors, which have been recently studied, may serve as safer alternatives to old monoamine oxidase inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Milad Nouraliei, Hamedreza Javadian, Khourshid Mehdizadeh, Nazanin Sheibanian, Abdollatif Shafaei Douk, Fatemeh Mohammadzadeh, Noushin Osouleddini
Summary: This study used molecular docking technique to investigate the interactions between phenelzine and its derivatives with monoamine oxidase, and explored the feasibility of carbon nanostructures as drug carriers. The results showed that nanostructures could serve as carriers for phenelzine derivatives and potentially be used as new drugs to inhibit monoamine oxidase.
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
(2023)
Article
Plant Sciences
Emmanuel Ayodeji Ayeni, Chao Ma, Yikao Hu, Xiaolin Bai, Yongmei Zhang, Xun Liao
Summary: This study found that the seeds of Nigella glandulifera contain Tauroside E and thymoquinone, which can inhibit monoamine oxidase B (MAO-B) and have therapeutic effects on Parkinson's disease.
Article
Biochemistry & Molecular Biology
Sandeep Kumar, Senthil Raja Ayyannan
Summary: This study successfully identified two potential MAO-B inhibitors using computational methods, which is significant for the treatment of diseases like Alzheimer's and Parkinson's.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Cem Yamali, Halise Inci Gul, Mehtap Tugrak Sakarya, Begum Nurpelin Saglik, Abdulilah Ece, Goksun Demirel, Merve Nenni, Serkan Levent, Ahmet Cihat Oner
Summary: This study synthesized a series of 4-((2-(aryl)-4-oxoquinazolin-3(4H)-yl)amino) benzenesulfonamides and investigated their inhibition potentials against MAOs. The most potent compounds 7 and 8 showed high selectivity and reversibility towards MAO-A, suggesting their potential as therapeutic agents for neurodegenerative diseases.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Koichi Takao, Yuri Takemura, Junko Nagai, Hitoshi Kamauchi, Kaori Hoshi, Ryo Mabashi, Yoshihiro Uesawa, Yoshiaki Sugita
Summary: A series of 3-styrylchromone derivatives were synthesized and evaluated for their inhibitory activities against monoamine oxidase (MAO) A and B. Compound 19 exhibited strong inhibitory activity against MAO-B with high selectivity index. QSAR analysis of the derivatives was conducted using Molecular Operating Environment and Dragon, showing significant correlations between the descriptors and MAO-B inhibitory activities.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Valentin Karabelyov, Violina T. Angelova, Martin Sharkov, Rositsa Mihaylova, Georgi Popov, Tania Pencheva, Vasil Manov, Miroslav Dangalov, Nadezhda Todorova, Magdalena Kondeva-Burdina
Summary: A series of new 1,3,4-oxadiazole 3a-3k and hydrazone hybrids 5a-5m were synthesized and evaluated for their activity against hMAO-A and hMAO-B in vitro. The results showed that compounds 3a and 3d exhibited effective inhibition of hMAO-B, with compound 3a showing the strongest enzyme-inhibiting effect. The neuroprotective effect of compound 3a was found to be due to hMAO-B inhibition based on in vitro, in vivo, and in silico results.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Medicinal
Asaf Evrim Evren, Demokrat Nuha, Sam Dawbaa, Begum Nurpelin Saglik, Leyla Yurttas
Summary: In this study, a new series of 2-thiazolyl hydrazone derivatives were synthesized and evaluated for their inhibitory effects on monoamine oxidase enzymes. Significant results were obtained, with several compounds showing potent and selective inhibition. Molecular docking, molecular dynamics simulations, and QSAR studies were performed to explore the structure-activity relationship. This study represents the first investigation of dual inhibitors on both MAO and aromatase enzymes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(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)