Article
Biochemistry & Molecular Biology
Fernanda M. F. Roleira, Saul C. Costa, Ana R. Gomes, Carla L. Varela, Cristina Amaral, Tiago Augusto, Georgina Correia-da-Silva, Isabella Romeo, Giosue Costa, Stefano Alcaro, Natercia Teixeira, Elisiario J. Tavares-da-Silva
Summary: New steroidal aromatase inhibitors (AIs) were synthesized and tested. Carbonyl group at C-11 position and C-ring epoxides were found to be more effective in aromatase inhibition. Compound 7 exhibited the strongest AI activity with an IC50 of 0.011 μM, outperforming the clinically used AI Exemestane with an IC50 of 0.050 μM. A-ring epoxides were found to be less potent than A-ring olefins. 713-methyl substitution was shown to be more effective than 7 alpha-methyl substitution in aromatase inhibition.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Nicola Relitti, A. Prasanth Saraswati, Giulia Chemi, Margherita Brindisi, Simone Brogi, Daniel Herp, Karin Schmidtkunz, Fulvio Saccoccia, Giovina Ruberti, Cristina Ulivieri, Francesca Vanni, Federica Sarno, Lucia Altucci, Stefania Lamponi, Manfred Jung, Sandra Gemma, Stefania Butini, Giuseppe Campiani
Summary: This study describes the synthesis of potent and selective quinolone-based histone deacetylase 6 (HDAC6) inhibitors, which showed good to excellent anticancer activity in cellular studies by inducing tumor cell death through modulation of protein deacetylation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Michael S. Malamas, Spiro Pavlopoulos, Shakiru O. Alapafuja, Shrouq Farah, Alexander Zvonok, Khadijah A. Mohammad, Jay West, Nicholas Thomas Perry, Dimitrios N. Pelekoudas, Girija Rajarshi, Christina Shields, Honrao Chandrashekhar, Jodi Wood, Alexandros Makriyannis
Summary: N-Acylethanolamines, particularly the palmitoylethanolamide hydrolyzed by NAAA, have been studied for their role in inflammation, pain, and drug addiction. Through synthesis and structure-activity relationship studies, potent inhibitors for hNAAA have been developed with high selectivity against other enzymes. These inhibitors have been identified as pharmacological tools for investigating the role of NAAA in various physiological processes.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Mark E. Layton, Jeffrey C. Kern, Timothy J. Hartingh, William D. Shipe, Izzat Raheem, Monika Kandebo, Robert P. Hayes, Sarah Huszar, Donnie Eddins, Bennett Ma, Joy Fuerst, Gordon K. Wollenberg, Jing Li, Jeff Fritzen, Georgia B. McGaughey, Jason M. Uslaner, Sean M. Smith, Paul J. Coleman, Christopher D. Cox
Summary: PDE10A is an important regulator of striatal signaling. Inhibition of PDE10A may offer a new treatment option for schizophrenia. This study describes the discovery of an isomeric pyrimidine series that led to the development of compound 18 (MK-8189), which is currently in Phase 2b clinical development for schizophrenia.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Ruifang Jia, Jian Zhang, Chiara Bertagnin, Srinivasulu Cherukupalli, Wei Ai, Xiao Ding, Zhuo Li, Jiwei Zhang, Han Ju, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu
Summary: The structural modifications at the 150-cavity of influenza virus neuraminidases can result in more potent oseltamivir derivatives, with compound 5c showing the most promising activity. In vitro and in vivo studies demonstrated low cytotoxicity and no acute toxicity of 5c, indicating its potential as a drug candidate.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Haiyan Yao, Quanping Guo, Mengran Wang, Rui Wang, Zhaoqing Xu
Summary: A novel class of molecules with a basic structure of pyrazole N-aryl sulfonate was designed and synthesized using a new pyrazole sulfonate synthetic method. Several compounds within this class showed excellent anti-inflammatory and analgesic activities, as well as selective COX-2 inhibitory properties. The LD50 of two compounds in mice were found to be greater than 2000 mg/kg in acute oral toxicity assays conducted in vivo.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Xue Zhong, Huiwen Deng, Min Long, Honglu Yin, Qiu Zhong, Shilong Zheng, Tao Gong, Ling He, Guangdi Wang, Qiu Sun
Summary: Berberine was discovered as a potent p300/CBP HAT inhibitor and showed inhibition of tumor growth. Novel analog 5d, derived from berberine, demonstrated high selectivity towards p300/CBP HAT and effectively suppressed tumor growth in animal models. Furthermore, liposomes-encapsulated 5d showed increased inhibition of tumor growth with good absorption properties in vivo.
BIOORGANIC CHEMISTRY
(2023)
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
Haoyu Zhang, Ping Xu, Ting Wang, Shiyu Wang, Weixia Li, Jianping Mao, Jian Wang, Fengjiao Zhang, Maosheng Cheng
Summary: In this study, a highly potent and selective CYP1B1 inhibitor C9 was obtained by structural modification, with an inhibitory activity of 2.7 nM against CYP1B1, and more than 37037 and 7407 fold selectivity over CYP1A1 and 1A2, respectively. Furthermore, C9 effectively restored the sensitivity of Taxol to A549/Taxol cells and inhibited cell migration. Molecular docking and molecular dynamics simulations showed that C9 formed necessary interactions in binding to CYP1B1 and could remain relatively stable.
NEW JOURNAL OF CHEMISTRY
(2023)
Editorial Material
Microbiology
Tom Boissavy, Dante Rotili, Thomas Mouveaux, Emmanuel Roger, El Moukthar Aliouat, Christine Pierrot, Sergio Valente, Antonello Mai, Mathieu Gissot
Summary: Toxoplasmosis is a significant health issue for immune-deficient individuals and newborns of infected mothers. New compounds with potent anti-parasitic activity have been discovered, which can serve as therapeutic targets for the treatment of toxoplasmosis.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Chemistry, Medicinal
Xian-Sen Huo, Xie-Er Jian, Jie Ou-Yang, Lin Chen, Fang Yang, Dong-Xin Lv, Wen-Wei You, Jin-Jun Rao, Pei-Liang Zhao
Summary: The novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives showed great potential as tubulin polymerization inhibitors, with high antiproliferative activity and selectivity against cancer cells. These compounds inhibit tumor cell growth by affecting the cell cycle, inducing apoptosis, and inhibiting tubulin polymerization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Jinyun Dong, Guang Huang, Qing Cui, Qingqing Meng, Shaoshun Li, Jiahua Cui
Summary: A series of 6,7,10-trimethoxy-alpha-naphthoflavone derivatives with variations in B ring were synthesized and screened, leading to the identification of fluorine-containing compound 15i as the most potent and selective CYP1B1 inhibitor. Amino-substituted derivative 13h showed potent inhibitory effect on CYP1B1 and increased water solubility compared to the lead molecule ANF.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Liqiang Fu, Jing Zhang, Bin Shen, Linglong Kong, Yingtao Liu, Wangyang Tu, Wenqian Wang, Xin Cai, Xiaotao Wang, Na Cheng, Mingxuan Xia, Tianyuan Zhou, Qian Liu, Yanping Xu, Jennifer Yang, Paul Gavine, Ulrike Philippar, Ricardo Attar, James P. Edwards, Jennifer D. Venable, Xuedong Dai
Summary: The study discusses the potent anti-proliferative effects of IRAK1 degraders on ABC DLBCL cells with MyD88 mutation, as well as their inhibitory effects on IRAK1 downstream signaling pathways, indicating the potential of these IRAK1 degraders for treating cancers dependent on IRAK1 scaffolding function.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Martina De Pascale, Lukas Bissegger, Chiara Tarantelli, Florent Beaufils, Alessandro Prescimone, Hayget Mohamed Seid Hedad, Omar Kayali, Clara Orbegozo, Luka Raguz, Thorsten Schaefer, Paul Hebeisen, Francesco Bertoni, Matthias P. Wymann, Chiara Borsari
Summary: The study identifies DHP and THP as isosteres of the morpholine moiety that can be used to generate novel TORKi drugs. Compound 11b is selected as a potent and selective mTOR kinase inhibitor with good metabolic stability and oral bioavailability. In cell experiments, compound 11b demonstrates dose-dependent anti-proliferative activity in splenic marginal zone lymphoma cell lines and synergistic effects with venetoclax.
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)
Review
Biochemistry & Molecular Biology
Angela Rampa, Silvia Gobbi, Federica Belluti, Alessandra Bisi
Summary: The unmet need for effective drugs for Alzheimer's disease is a major challenge in drug discovery. Drug repurposing has become an attractive approach to obtain new medications and reduce time and economic burden. Different classes of drugs show promising effects on neurodegenerative diseases, with structural modifications resulting in multifunctional compounds.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Jessica Caciolla, Giovanna Picone, Giovanna Farruggia, Dario Valenti, Angela Rampa, Emil Malucelli, Federica Belluti, Alfonso Trezza, Ottavia Spiga, Stefano Iotti, Silvia Gobbi, Concettina Cappadone, Alessandra Bisi
Summary: In this study, a new library of derivatives with a polycyclic scaffold was designed and synthesized as potential MDR reverting agents and antitumor agents. The research focused on the role of the spacer connecting the polycyclic core with nitrogen-containing groups, leading to the discovery of compounds with significant reverting potency. Additionally, these compounds exhibited multifaceted anticancer properties and dual in vitro activity, showing both revertant and antitumor effects.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Maria Galvez-Llompart, Riccardo Ocello, Laura Rullo, Serena Stamatakos, Irene Alessandrini, Riccardo Zanni, Inaki Tunon, Andrea Cavalli, Sanzio Candeletti, Matteo Masetti, Patrizia Romualdi, Maurizio Recanatini
Summary: The study explores inhibiting the JAK-STAT signaling pathway as a potential strategy for treating autoimmune and inflammatory disorders. Through computational molecular topology, docking, and molecular dynamics simulations, novel JAK inhibitors were identified, with two hit compounds showing promising results compared to the reference drug Tofacitinib.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Review
Biochemistry & Molecular Biology
Silvia Gobbi, Federica Belluti, Angela Rampa, Alessandra Bisi
Summary: Naturally occurring flavonoids are bioactive compounds found in plants, used for treating various pathologies. They are considered valuable sources for lead compounds and synthetic compounds development. There has been a renewed interest in flavonoid-based structures, particularly in anticancer research.
Article
Biochemistry & Molecular Biology
Serena Montanari, Marco Allara, Laura Scalvini, Magdalena Kostrzewa, Federica Belluti, Silvia Gobbi, Marina Naldi, Silvia Rivara, Manuela Bartolini, Alessia Ligresti, Alessandra Bisi, Angela Rampa
Summary: Recent studies have revealed the connection between the endocannabinoid system (eCS) and neuroprotection, suggesting its involvement in regulating cognitive processes and the pathophysiology of Alzheimer's disease. Designed and synthesized coumarin-based compounds showed promising potential as multitarget agents for combating complex diseases like AD.
Article
Biochemistry & Molecular Biology
Martina Rossi, Concettina Cappadone, Giovanna Picone, Alessandra Bisi, Giovanna Farruggia, Federica Belluti, Paolo Blasi, Silvia Gobbi, Emil Malucelli
Summary: This study reports a series of new compounds with anti-osteosarcoma activity. The antitumor activity, cell cycle progression, and apoptosis induction of these compounds were evaluated using innovative techniques and methods. Among the tested compounds, 1e, 1q, and 1r showed the most promising antitumor properties.
Article
Chemistry, Medicinal
Jessica Caciolla, Silvia Martini, Angelo Spinello, Federica Belluti, Alessandra Bisi, Nadia Zaffaroni, Alessandra Magistrato, Silvia Gobbi
Summary: This study developed a new generation of dualsteric non-steroidal aromatase inhibitors (AIs) and conducted extensive structural characterization at the molecular level. The most active inhibitor was found to effectively lock onto the enzyme's active site, overcoming resistance issues encountered in treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Francesca Seghetti, Federica Belluti, Angela Rampa, Silvia Gobbi, Jenny Legac, Silvia Parapini, Nicoletta Basilico, Alessandra Bisi
Summary: The study focused on designing a series of hybrid molecules to combat malaria, with compounds 1b and 1c showing the highest in vitro activity, particularly against resistant strains of Plasmodium falciparum.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Silvia Gobbi, Silvia Martini, Riccardo Rozza, Angelo Spinello, Jessica Caciolla, Angela Rampa, Federica Belluti, Nadia Zaffaroni, Alessandra Magistrato, Alessandra Bisi
Summary: In this study, novel compounds with dual AR and ER activity were designed by modifying flavonoid-related compounds. Compounds 3b and 4a showed promising submicromolar activity against both targets. Computational studies confirmed the feasibility of using multi-target approaches for ER+ BC treatment. The homoisoflavone core emerged as a valuable scaffold for the design of multifunctional compounds.
Article
Medicine, Research & Experimental
Maurizio Recanatini, Luca Menestrina
Summary: Diseases can be considered as emergent properties of living systems stemming from their complexity, and the use of network models has been introduced to describe drug-disease systems and make predictions about them. This article reviews recent examples of network science tools and predictive models in addressing drug-disease systems.
WIRES MECHANISMS OF DISEASE
(2023)
