Article
Crystallography
Sang Loon Tan, Yee Seng Tan, Jia Hui Ng, Anton V. Dolzhenko, Edward R. T. Tiekink
Summary: Two monoclinic polymorphs of a bioactive pyrazolo[3,4-d]pyrimidine derivative, named α (from methanol) and β (from ethanol, n-propanol and iso-propanol), were isolated and characterized by X-ray crystallography and computational chemistry techniques. The different conformations observed in the crystals are due to the molecular packing, which is determined by geometry-optimization calculations. The β-form is found to be more stable by 11 kJ/mol based on lattice energy calculations.
Article
Chemistry, Medicinal
Jakob Bouton, Ludmila Ferreira de Almeida Fiuza, Camila Cardoso Santos, Maria Angela Mazzarella, Maria de Nazare Correia Soeiro, Louis Maes, Izet Karalic, Guy Caljon, Serge Van Calenbergh
Summary: Chagas disease and visceral leishmaniasis are neglected tropical diseases with insufficient current treatments, requiring the development of new drugs. This study reports the design and synthesis of pyrazolo[3,4-d]pyrimidine nucleosides as potential antiparasitic agents, with one compound showing activity in an acute Chagas disease mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Barbara Cacciari, Romeo Romagnoli, Arianna Romani, Alessandro Trentini, Stefania Hanau
Summary: The study aimed to identify new compounds for potential antiproliferative drug candidates, with the most effective compounds showing selectivity against cancer cells. The presence of a substituted pyrazolo[3,4-d]pyrimidine core and substituents at the thiol function in the 6-position were found to be essential for this antiproliferative activity.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yuancheng Mao, Eun Lee, Xiaohui Yang, Eun Ju Bae, Raok Jeon, Byung-Hyun Park
Summary: The study reveals the role of PAK4 in liver I/R injury, and identifies SPA7012 as a potential PAK4 inhibitor that attenuates I/R damage, stabilizes Nrf2, and reduces hepatocyte apoptosis and inflammation.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Ibrahim F. Nassar, Mohammed T. Abdel Aal, Wael A. El-Sayed, Mahmoud A. E. Shahin, Elsayed G. E. Elsakka, Mahmoud Mohamed Mokhtar, Maghawry Hegazy, Mohamed Hagras, Asmaa A. Mandour, Nasser S. M. Ismail
Summary: CDK2 inhibition is a promising target for cancer treatment, and a new set of small molecules have been designed and synthesized as potential CDK2 targeting compounds. These compounds showed superior cytotoxic activities against certain cancer cell lines and demonstrated significant inhibitory activity against CDK2.
Article
Cell Biology
Seok Choi, Hyunhyo Seo, Kyungmin Lee, Dong Hoon Shin, Mei Jin Wu, Wenhao Wu, Xingyou Huang, Jingwei Zhang, Chansik Hong, Jae Yeoul Jun
Summary: The study revealed the presence of HCN channels in colonic ICC and their involvement in generating pacemaking potentials, suggesting that HCN channels could be therapeutic targets for disturbed colonic motility disorders.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Gioele Capillo, Eugenia R. Lauriano, Jose M. Icardo, Prabhugouda Siriyappagouder, Michal Kuciel, Stelios Karapanagiotis, Giacomo Zaccone, Jorge M. O. Fernandes
Summary: HCN channels are proteins that regulate cardiac pacemaker activity and synaptic transmission. Research on the pacemaker system in the heart of wild Atlantic cod revealed the potential role of intracardiac neurons in modulating pacemaking.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Morihiro Shimizu, Xinya Mi, Futoshi Toyoda, Akiko Kojima, Wei-Guang Ding, Yutaka Fukushima, Mariko Omatsu-Kanbe, Hirotoshi Kitagawa, Hiroshi Matsuura
Summary: Propofol acts as an allosteric modulator of cAMP-dependent gating in HCN channels, affecting the amplitude and voltage dependence of the channel opening.
Article
Biochemistry & Molecular Biology
You-Guang Zheng, Xin Pei, De-Xin Xia, Yuan-Bo Wang, Ping Jiang, Lin An, Tong-Hui Huang, Yun-Sheng Xue
Summary: Novel 2H-imidazo [1, 2-c] pyrazolo [3, 4-e] pyrimidine derivative compound 9b exhibited high antiproliferative activities against K562 and U937 cells, suggesting it may be a potential anticancer agent that deserves further investigation.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Qinjie Shi, Yuanyuan Ji, Yanxia Shi, Zhenjiang Zhao, Weiping Zhu, Yufang Xu, Baoju Li, Xuhong Qian
Summary: Research on new plant activators, such as 1-methyl-4-amino-pyrazolo [3,4-d]pyrimidine, has shown potential in inducing the ISR immune system in plants. The introduction of fluorine atom greatly enhances the induction activity of pyrazolo [3,4-d]pyrimidine derivatives, leading to broad-spectrum induced resistance, although without direct antibacterial activity in vitro. This suggests a promising approach in developing new pesticides with enhanced resistance in both defending pathogens and insects.
Article
Biochemistry & Molecular Biology
Guanglong Li, Keya Xiao, Man Shi, Jing Shuai, Zhiping Xu, Zhong Li, Jiagao Cheng
Summary: A new series of 4-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesized based on the fipronil low energy conformation by scaffold hopping strategy. Physicochemical properties calculation, insecticidal assay and binding mode studies were performed. The target compounds displayed lower insecticidal activities than fipronil, possibly due to the differences in binding modes between these compounds and fipronil.
CHEMISTRY & BIODIVERSITY
(2022)
Article
Biochemistry & Molecular Biology
Enrico Rango, Fabio Pastorino, Chiara Brignole, Arianna Mancini, Federica Poggialini, Salvatore Di Maria, Claudio Zamperini, Giulia Iovenitti, Anna Lucia Fallacara, Samantha Sabetta, Letizia Clementi, Massimo Valoti, Silvia Schenone, Adriano Angelucci, Mirco Ponzoni, Elena Dreassi, Maurizio Botta
Summary: Si306, an anticancer agent, has shown favorable activity against neuroblastoma models. However, its sub-optimal aqueous solubility poses a limitation for its development. In this study, Si306 was encapsulated into liposomes and modified with an antibody specific for neuroblastoma cells. The modified liposomes demonstrated increased cellular targeting and cytotoxic activity. In animal experiments, Si306 encapsulated in targeted liposomes showed significantly higher tumor uptake and improved survival rates.
Article
Biology
Sofija Jovanovic Stojanov, Ana Kostic, Mila Ljujic, Ema Lupsic, Silvia Schenone, Milica Pesic, Jelena Dinic
Summary: Drug resistance is a major challenge in treating glioblastoma. Autophagy plays a crucial role in drug resistance, and the use of autophagy inhibitors can enhance the effectiveness of targeted therapy. This study shows that two Src tyrosine kinase inhibitors can induce autophagy in glioblastoma cells, and inhibiting autophagy can increase the anticancer effects of these inhibitors.
Article
Biochemistry & Molecular Biology
Eunkyung Jung, Ruben Soto-Acosta, Robert J. Geraghty, Liqiang Chen
Summary: In this study, an alternative substitution pattern centered on a 1H-pyrazolo[3,4-d]pyrimidine scaffold was discovered to exhibit low micromolar antiviral activity against Zika virus. Structure-activity relationship studies revealed that an electron-withdrawing group at the para position of ring A enhanced the antiviral activity. Compounds 6 and 13 were identified as potential anti-ZIKV agents with low micromolar antiviral activity and relatively low cytotoxicity.
Review
Biochemistry & Molecular Biology
Edwin Jarratt-Barnham, Limin Wang, Youzheng Ning, Julia M. Davies
Summary: Plant CNGCs are tetrameric cation channels activated by cNMPs like cAMP and cGMP. Arabidopsis thaliana encodes 20 CNGC subunits involved in development, stress response, and immunity. Recent findings show that CNGC subunits form heterotetrameric complexes with distinct behavior, affecting signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)