Article
Chemistry, Medicinal
Dawid Panek, Anna Pasieka, Gniewomir Latacz, Paula Zareba, Michal Szczech, Justyna Godyn, Fabien Chantegreil, Florian Nachon, Xavier Brazzolotto, Anna Skrzypczak-Wiercioch, Maria Walczak, Magdalena Smolik, Kinga Salat, Georg Hoefner, Klaus Wanner, Anna Wieckowska, Barbara Malawska
Summary: A highly selective hBuChE inhibitor (29) with potential benefits for treating Alzheimer's disease has been identified through extensive in vitro and in vivo evaluations.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Filip Pidany, Jana Kroustkova, Abdullah Al Mamun, Daniela Suchankova, Xavier Brazzolotto, Florian Nachon, Fabien Chantegreil, Rafael Dolezal, Lenka Pulkrabkova, Lubica Muckova, Martina Hrabinova, Vladimir Finger, Martin Kufa, Ondrej Soukup, Daniel Jun, Jaroslav Jenco, Jiri Kunes, Lucie Novakova, Jan Korabecny, Lucie Cahlikova
Summary: This study focuses on the design, synthesis, and in vitro evaluation of novel hBChE inhibitors for the treatment of late-stage AD. Compound 87 exhibits promising BChE inhibitory activity and low cytotoxicity, making it a potential lead compound for further development. Crystallographic and QSAR analyses provide insights into the binding mode and structure-activity relationship of these compounds.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Paptawan Suwanhom, Jirakrit Saetang, Pasarat Khongkow, Teerapat Nualnoi, Varomyalin Tipmanee, Luelak Lomlim
Summary: A quinoxaline scaffold showed various bioactivities in pharmacotherapeutic interests. In this study, twelve quinoxaline derivatives were synthesized and evaluated as new acetylcholinesterase inhibitors, showing potent inhibitory activities against AChE and BChE, preferring to bind with PAS site.
Article
Chemistry, Medicinal
Chaoming Wang, Jinman Zhang, Xianfeng Wei, Mengke Yang, Weiping Ma, Rilei Yu, Ming Liu, Tao Jiang
Summary: In this study, 19 Lissodendrins B analogues were designed and synthesized, and their reversal activity of ATP-Binding Cassette Subfamily B Member 1 (ABCB1)-mediated multidrug resistance (MDR) was tested. Among them, compound D-1 showed the strongest synergistic effect with doxorubicin (DOX) and effectively reversed ABCB1-mediated drug resistance. Mechanistic studies revealed that the synergy was mainly due to the inhibition of ABCB1 efflux function, leading to increased intracellular accumulation of DOX. These findings suggest that compound D-1 and its derivatives have potential as MDR reversal agents by acting as ABCB1 inhibitors in clinical therapeutics.
Article
Biochemistry & Molecular Biology
Abdullah Al Mamun, Filip Pidany, Daniela Hulcova, Jana Marikova, Tomas Kucera, Monika Schmidt, Maria Carmen Catapano, Martina Hrabinova, Daniel Jun, Lubica Muckova, Jiri Kunes, Jiri Janousek, Rudolf Andrys, Lucie Novakova, Rozalie Perinova, Negar Maafi, Ondrej Soukup, Jan Korabecny, Lucie Cahlikova
Summary: Alzheimer's disease is currently treated with cholinesterase inhibitors and memantine, but targeting butyrylcholinesterase (BuChE) has shown promise in advanced stages of the disease. A series of compounds were synthesized based on Amaryllidaceae alkaloids, showing strong inhibition of human BuChE with good selectivity over AChE. Further studies are needed to explore the potential of these compounds for Alzheimer's disease treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Diego A. S. Yamazaki, Andrew M. F. Rozada, Paula Barea, Elaine C. Reis, Ernani A. Basso, Maria Helena Sarragiotto, Flavio A. V. Seixas, Gisele F. Gauze
Summary: A novel series of arylcarbamate-N-acylhydrazones derivatives have been designed and synthesized as potential anti-cholinesterase agents, with compound 10c identified as a low-cost promising candidate for a drug prototype for AD treatment.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Chenghao Pan, Wenwen Nie, Jiao Wang, Jiamin Du, Zhichao Pan, Jian Gao, Yang Lu, Jinxin Che, Hong Zhu, Haibin Dai, Binhui Chen, Qiaojun He, Xiaowu Dong
Summary: This study developed a series of quinazoline derivatives based on the FGFR4 inhibitor BLU9931, with compound 35a showing improved stability in liver microsomes and induced apoptosis via FGFR4 signaling pathway blockage. Computational simulation provided insights into the binding mode of compound 35a to FGFR4 protein, explaining its high potency and metabolic stability.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Subhabrata Chaudhury, Penchala Narasimharao Meka, Monimoy Banerjee, Caitlin N. Kent, Brian S. J. Blagg
Summary: Hsp90 is responsible for folding and trafficking proteins associated with cancer progression. Existing inhibitors have undesired effects, leading to the development of isoform-selective inhibitors. Research shows that Hsp90 beta-selective inhibitors can overcome the detriments of pan-inhibition of Hsp90.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Medicinal
Rui Zhang, Heng Li, Xianglei Zhang, Jian Li, Haixia Su, Qiukai Lu, Guangyu Dong, Huixia Dou, Chen Fan, Zhanni Gu, Qianwen Mu, Wei Tang, Yechun Xu, Hong Liu
Summary: A series of novel tetrahydroisoquinoline derivatives were developed and compound 36 exhibited significant inhibitory effects against PDE4D enzymatic activity and TNF-α release, showing more significant efficacy in improving psoriasis-like skin inflammation compared to calcipotriol.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sumei Ren, Minmin Zhang, Yujie Wang, Jia Guo, Junfei Wang, Yingxia Li, Ning Ding
Summary: Novel cabazitaxel analogues with potent cytotoxicity against various cell lines were synthesized and evaluated. In vivo assessment on SCID mice showed two analogues had similar antitumor activity to cabazitaxel, with one potentially serving as a strong drug candidate based on preliminary studies.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Carmen Lammi, Enrico M. A. Fassi, Marco Manenti, Marta Brambilla, Maria Conti, Jianqiang Li, Gabriella Roda, Marina Camera, Alessandra Silvani, Giovanni Grazioso
Summary: Proprotein convertase subtilisin/kexin 9 (PCSK9) is a key target for the treatment of hypercholesterolemia and cardiovascular diseases. In this study, we discovered Rim13, a polyimidazole derivative that inhibits the interaction between PCSK9 and LDLR. Through computational design, we optimized the shape of PCSK9/ligand complementarity and identified potent diimidazole derivatives. Compound Dim16 showed improved PCSK9 inhibitory activity and some compounds in this series also showed hypocholesterolemic activity by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Mizushi Yanagihara, Kenichi Murai, Naoki Kishimoto, Towa Abe, Shogo Misumi, Mitsuhiro Arisawa
Summary: The total synthesis and biological evaluation of the marine sesterterpenoid ansellone A, along with its analogues, were successfully carried out. The key to the success of the synthetic route was the Prins cyclization reaction enabled by the strategic use of the TfO group to stabilize the acid-labile tertiary allylic alcohol. The structure-activity relationship study indicated that the alcohol analogue exhibited more potent activity than compound 1.
Article
Chemistry, Medicinal
Tuan Xu, Shuaizhang Li, Andrew J. Li, Jinghua Zhao, Srilatha Sakamuru, Wenwei Huang, Menghang Xia, Ruili Huang
Summary: In this study, machine learning models were developed to predict novel AChE and BChE inhibitors. The models showed good performance in virtual screening and increased the hit rate of assay. A total of 88 novel AChE and 126 novel BChE inhibitors were identified, with significant inhibitory effects. Structure-activity relationship analysis revealed scaffolds for chemistry design and optimization.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Plant Sciences
Shi-Xing Miao, Lin-Xi Wan, Zhen-Xiang He, Xian-Li Zhou, Xiaohuan Li, Feng Gao
Summary: The first systematic direct diversification of a complex natural product by metal-catalyzed N-H functionalization was conducted, resulting in the synthesis of a new series of N-aryl-huperzine A analogues with good AChE inhibitory activity. Compound 30 showed the most potent AChE inhibition activity and could be a promising lead compound for Alzheimer's disease drug development.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Chemistry, Medicinal
Guang-Jing Feng, Yang-Fan Guo, Yuming Tang, Min Li, Yufei Jia, Zhimeng Li, Shuangshuang Wang, Hongmei Liu, Yuzhou Wu, Hai Dong
Summary: The potential of thioglucoside analogues as antidiabetic drugs was investigated in this study. The analogues showed good stability, low toxicity, and high inhibitory activity, making them promising candidates for new gliflozin drugs. Additionally, the synthesis of these analogues is simple, efficient, and cost-effective.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
J. Benjamn Garcia-Vazquez, Daphne E. Gonzalez-Juarez, Martha S. Morales-Rios, Oscar R. Suarez-Castillo, Yolanda Mora-Perez
MAGNETIC RESONANCE IN CHEMISTRY
(2015)
Article
Chemistry, Inorganic & Nuclear
Reyna E. Cordero-Rivera, Myriam Melendez-Rodriguez, Oscar R. Suarez-Castillo, Claudia I. Bautista-Hernandez, Nayely Trejo-Carbajal, Julian Cruz-Borbolla, Luis E. Castelan-Duarte, Martha S. Morales-Rios, Pedro Joseph-Nathan
TETRAHEDRON-ASYMMETRY
(2015)
Article
Chemistry, Inorganic & Nuclear
Claudia I. Bautista-Hernandez, Reyna E. Cordero-Rivera, Erick A. Zuniga-Estrada, Nayely Trejo-Carbajal, Myriam Melendez-Rodriguez, Oscar R. Suarez-Castillo, Maricruz Sanchez-Zavala, Martha S. Morales-Rios, Pedro Joseph-Nathan
TETRAHEDRON-ASYMMETRY
(2016)
Article
Chemistry, Physical
J. Benjamin Garcia-Vazquez, Angel E. Banuelos-Hernandez, Joel J. Trujillo-Serrato, Oscar R. Suarez-Castillo, Armando Ariza-Castolo, Martha S. Morales-Rios
JOURNAL OF MOLECULAR STRUCTURE
(2017)
Article
Chemistry, Physical
Humberto Mendoza-Figueroa, Gelacio Martinez-Gudino, Jorge E. Villanueva-Luna, Joel J. Trujillo-Serrato, Martha S. Morales-Rios
JOURNAL OF MOLECULAR STRUCTURE
(2017)
Article
Chemistry, Inorganic & Nuclear
Claudia I. Bautista-Hernandez, Nayely Trejo-Carbajal, Erick A. Zuniga-Estrada, Alberto Aristeo-Dominguez, Myriam Melendez-Rodriguez, Oscar R. Suarez-Castillo, Maricruz Sanchez-Zavala, Julian Cruz-Borbolla, Martha S. Morales-Rios, Pedro Joseph-Nathan
TETRAHEDRON-ASYMMETRY
(2017)
Article
Chemistry, Medicinal
Humberto L. Mendoza-Figueroa, Maria Trinidad Serrano-Alva, Gerardo Aparicio-Ozores, Gelacio Martinez-Gudino, Oscar R. Suarez-Castillo, Nadia A. Perez-Rojas, Martha S. Morales-Rios
MEDICINAL CHEMISTRY RESEARCH
(2018)
Article
Chemistry, Organic
Alberto Aristeo-Dominguez, Myriam Melendez-Rodriguez, Oscar R. Suarez Castillo, Yaneth M. A. Contreras-Martinez, Lizbeth Suarez-Ramirez, Nayely Trejo-Carbajal, Martha S. Morales-Rios, Pedro Joseph-Nathan
Article
Chemistry, Multidisciplinary
Nury Perez-Hernandez, Celina Alvarez-Cisneros, Carlos M. Cerda-Garcia-Rojas, Martha S. Morales-Rios, Pedro Joseph-Nathan
MAGNETIC RESONANCE IN CHEMISTRY
(2013)
Article
Chemistry, Multidisciplinary
Jose J. Cordero-Perez, Sandra L. de Ita-Gutierrez, Nayely Trejo-Carbajal, Myriam Melendez-Rodriguez, Maricruz Sanchez-Zavala, Nury Perez-Hernandez, Martha S. Morales-Rios, Pedro Joseph-Nathan, Oscar R. Suarez-Castillo
MAGNETIC RESONANCE IN CHEMISTRY
(2014)
Article
Chemistry, Multidisciplinary
Celina Alvarez-Cisneros, Marcelo A. Munoz, Oscar R. Suarez-Castillo, Nury Perez-Hernandez, Carlos M. Cerda-Garcia-Rojas, Martha S. Morales-Rios, Pedro Joseph-Nathan
MAGNETIC RESONANCE IN CHEMISTRY
(2014)
Article
Chemistry, Organic
Daphne E. Gonzalez-Juarez, J. Benjamin Garcia-Vazquez, Violeta Zuniga-Garcia, Joel J. Trujillo-Serrato, Oscar R. Suarez-Castillo, Pedro Joseph-Nathan, Martha S. Morales-Rios
Article
Chemistry, Physical
Gelacio Martinez-Gudino, Nadia A. Perez-Rojas, Joel J. Trujillo-Serrato, Yolanda Mora-Perez, Oscar R. Suarez-Castillo, Martha S. Morales-Rios
JOURNAL OF MOLECULAR STRUCTURE
(2019)
Article
Chemistry, Physical
Martha S. Morales-Rios, Daphne E. Gonzalez-Juarez, Gelacio Martinez-Gudino, Nury Perez-Hernandez, Luz Maria Del Razo, Humberto L. Mendoza-Figueroa, J. Benjamin Garcia-Vazquez
JOURNAL OF MOLECULAR STRUCTURE
(2020)
Article
Chemistry, Medicinal
Martha S. Morales-Rios, Ernesto Rivera-Becerril, Perla Y. Lopez-Camacho, Nadia A. Perez-Rojas, Oscar R. Suarez-Castillo
NATURAL PRODUCT COMMUNICATIONS
(2012)