Sequential release of interacting proteins and Ub-modifying enzymes by disulfide heterotypic ubiquitin reagents
In this study, we employed the bifunctional molecule-assisted (CAET) strategy to develop a type of disulfide bond-activated heterotypic Ub reagents, which allowed to enrich heterotypic Ub-interacting proteins and modifying enzymes simultaneously. The sequential release of readers which are non-covalently bound and writers or erasers which are covalently conjugated by using urea and reductant, respectively, combined with label-free quantitative (LFQ) MS indicated that these heterotypic Ub reagents would facilitate future investigations into functional roles played by heterotypic Ub chains.PMID:38387394 | DOI:10.1016/j.bioor...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Hongyi Cai Xiangwei Wu Junxiong Mao Zebin Tong Dingfei Yan Yicheng Weng Qingyun Zheng Source Type: research
Anti-diabetic and anti-inflammatory indole diterpenes from the marine-derived fungus Penicillium sp. ZYX-Z-143
Bioorg Chem. 2024 Feb 16;145:107205. doi: 10.1016/j.bioorg.2024.107205. Online ahead of print.ABSTRACTSeven new indole-diterpenoids, penpaxilloids A-E (1-5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8-27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by ...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Lu-Ting Dai Li Yang Jiao-Cen Guo Qing-Yun Ma Qing-Yi Xie Li Jiang Zhi-Fang Yu Hao-Fu Dai You-Xing Zhao Source Type: research
3-Amide- β-carbolines block the cell cycle by targeting CDK2 and DNA in tumor cells potentially as anti-mitotic agents
Bioorg Chem. 2024 Feb 16;145:107216. doi: 10.1016/j.bioorg.2024.107216. Online ahead of print.ABSTRACTβ-Carboline alkaloids are natural and synthetic products with outstanding antitumor activity. C3 substituted and dimerized β-carbolines exert excellent antitumor activity. In the present research, 37 β-carboline derivatives were synthesized and characterized. Their cytotoxicity, cell cycle, apoptosis, and CDK2- and DNA-binding affinity were evaluated. β-Carboline monomer M3 and dimer D4 showed selective activity and higher cytotoxicity in tumor cells than in normal cells. Structure-activity relationships (SAR) indicate...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Dongming Zhi Zhiyuan An Lishan Li Chaojia Zheng Xiaorong Yuan Yu Lan Jinghan Zhang Yujie Xu Huiya Ma Na Li Junru Wang Source Type: research
Astraoleanosides E-P, oleanane-type triterpenoid saponins from the aerial parts of Astragalus membranaceus Bunge and their β-glucuronidase inhibitory activity
In this study, a phytochemical characterization of the aerial parts of A. membranaceusled to the isolation of 29 oleanane-type triterpenoid saponins, including 11 new compounds named astraoleanosides E-P (6-9, 13, 14, 18-22), as well as 18 known ones. The structures of these compounds were elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. Among them, astraoleanoside H (9) and cloversaponin III (15) demonstrated the most potent β-glucuronidase inhibitory activities, with IC50 values of 21.20 ± 0.75 and 9.05 ± 0.47 µM, respectively, compared to the positive control d-sa...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Manh Khoa Nguyen Viet Phong Nguyen Seo Young Yang Byung Sun Min Jeong Ah Kim Source Type: research
Novel spiroindoline derivatives targeting aldose reductase against diabetic complications: Bioactivity, cytotoxicity, and molecular modeling studies
Bioorg Chem. 2024 Feb 19;145:107221. doi: 10.1016/j.bioorg.2024.107221. Online ahead of print.ABSTRACTDespite significant developments in therapeutic strategies, Diabetes Mellitus remains an increasing concern, leading to various complications, e.g., cataracts, neuropathy, retinopathy, nephropathy, and several cardiovascular diseases. The polyol pathway, which involves Aldose reductase (AR) as a critical enzyme, has been focused on by many researchers as a target for intervention. On the other hand, spiroindoline-based compounds possess remarkable biological properties. This guided us to synthesize novel spiroindoline oxad...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Özcan Güleç C üneyt Türkeş Mustafa Arslan Yeliz Demir Busra Dincer Abdulilah Ece Ömer İrfan Küfrevioğlu Şükrü Beydemir Source Type: research
Multi-target rational design and synthesis of novel diphenyl-tethered pyrazolopyrimidines targeting EGFR and topoisomerase II with potential DNA intercalation and apoptosis induction
Bioorg Chem. 2024 Feb 17;145:107223. doi: 10.1016/j.bioorg.2024.107223. Online ahead of print.ABSTRACTHerein, we envisioned the design and synthesis of novel pyrazolopyrimidines (confirmed by elemental analysis, 1H and 13C NMR, and mass spectra) as multitarget-directed drug candidates acting as EGFR/TOPO II inhibitors, DNA intercalators, and apoptosis inducers. The target diphenyl-tethered pyrazolopyrimidines were synthesized starting from the reaction of phenyl hydrazine and ethoxymethylenemalononitrile to give aminopyrazole-carbonitrile 2. The latter hydrolysis with NaOH and subsequent reaction with 4-chlorobenzaldhyde a...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Ahmed A Gaber Ayman Abo Elmaaty Marwa Sharaky Aliaa A Mosa Abdullah Yahya Abdullah Alzahrani Saad Shaaban Wagdy M Eldehna Ahmed A Al-Karmalawy Source Type: research
The antimicrobial potential of adarotene derivatives against Staphylococcus aureus strains
Bioorg Chem. 2024 Feb 18;145:107227. doi: 10.1016/j.bioorg.2024.107227. Online ahead of print.ABSTRACTMultidrug-resistant (MDR) pathogens are severely impacting our ability to successfully treat common infections. Here we report the synthesis of a panel of adarotene-related retinoids showing potent antimicrobial activity on Staphylococcus aureus strains (including multidrug-resistant ones). Fluorescence and molecular dynamic studies confirmed that the adarotene analogues were able to induce conformational changes and disfunctions to the cell membrane, perturbing the permeability of the phospholipid bilayer. Since the major...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Salvatore Princiotto Bruno Casciaro Alvaro G Temprano Loana Musso Francesca Sacchi Maria Rosa Loffredo Floriana Cappiello Federica Sacco Giammarco Raponi Virginia Perez Fernandez Teresa Iucci Maria Luisa Mangoni Mattia Mori Sabrina Dallavalle Claudio Pisa Source Type: research
Effect of N-o-nitrobenzylation on conformation and membrane permeability of linear peptides
In this study, we explored the potential of the photoremovable o-nitrobenzyl (oNB) group as a tool to manipulate the membrane permeability and regulate the conformation of linear peptides by means of experimental and computational studies. We found that the introduction of one or more oNB groups markedly increased the permeability and altered the conformation, as compared to the corresponding unmodified peptides. We thoroughly investigated the impact of peptide length, number of oNB group, oNB insertion position, and introduction of N- and C-terminal protecting groups on the passive membrane permeability by means of parall...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Zhihan Huang Mayumi Ishii Eri Watanabe Kayoko Kanamitsu Kempei Tai Hiroyuki Kusuhara Tomohiko Ohwada Yuko Otani Source Type: research
Monoamine oxidase B activatable red fluorescence probe for bioimaging in cells and zebrafish
Bioorg Chem. 2024 Jan 30;145:107156. doi: 10.1016/j.bioorg.2024.107156. Online ahead of print.ABSTRACTA real-time and specific for the detection of Monoamine Oxidase B (MAO-B) to investigate the MAO-B-relevant disease development and treatment process is urgently desirable. Here, we utilized MAO-B to catalyze the conversion of propylamino groups to aldehyde groups, which was then quickly followed by a β-elimination process to produce fluorescent probes (FNJP) that may be used to detect MAO-B in vitro and in vivo. The FNJP probe possesses unique properties, including favorable reactivity (Km = 10.8 μM), high cell permeabi...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Zhengmin Yang Tiantian Zhong Qingyuan Mo Jiman He Jia Chong Xianyun Hu Shulin Zhao Jiangke Qin Source Type: research
Sequential release of interacting proteins and Ub-modifying enzymes by disulfide heterotypic ubiquitin reagents
In this study, we employed the bifunctional molecule-assisted (CAET) strategy to develop a type of disulfide bond-activated heterotypic Ub reagents, which allowed to enrich heterotypic Ub-interacting proteins and modifying enzymes simultaneously. The sequential release of readers which are non-covalently bound and writers or erasers which are covalently conjugated by using urea and reductant, respectively, combined with label-free quantitative (LFQ) MS indicated that these heterotypic Ub reagents would facilitate future investigations into functional roles played by heterotypic Ub chains.PMID:38387394 | DOI:10.1016/j.bioor...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Hongyi Cai Xiangwei Wu Junxiong Mao Zebin Tong Dingfei Yan Yicheng Weng Qingyun Zheng Source Type: research
Anti-diabetic and anti-inflammatory indole diterpenes from the marine-derived fungus Penicillium sp. ZYX-Z-143
Bioorg Chem. 2024 Feb 16;145:107205. doi: 10.1016/j.bioorg.2024.107205. Online ahead of print.ABSTRACTSeven new indole-diterpenoids, penpaxilloids A-E (1-5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8-27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by ...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Lu-Ting Dai Li Yang Jiao-Cen Guo Qing-Yun Ma Qing-Yi Xie Li Jiang Zhi-Fang Yu Hao-Fu Dai You-Xing Zhao Source Type: research
3-Amide- β-carbolines block the cell cycle by targeting CDK2 and DNA in tumor cells potentially as anti-mitotic agents
Bioorg Chem. 2024 Feb 16;145:107216. doi: 10.1016/j.bioorg.2024.107216. Online ahead of print.ABSTRACTβ-Carboline alkaloids are natural and synthetic products with outstanding antitumor activity. C3 substituted and dimerized β-carbolines exert excellent antitumor activity. In the present research, 37 β-carboline derivatives were synthesized and characterized. Their cytotoxicity, cell cycle, apoptosis, and CDK2- and DNA-binding affinity were evaluated. β-Carboline monomer M3 and dimer D4 showed selective activity and higher cytotoxicity in tumor cells than in normal cells. Structure-activity relationships (SAR) indicate...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Dongming Zhi Zhiyuan An Lishan Li Chaojia Zheng Xiaorong Yuan Yu Lan Jinghan Zhang Yujie Xu Huiya Ma Na Li Junru Wang Source Type: research
Astraoleanosides E-P, oleanane-type triterpenoid saponins from the aerial parts of Astragalus membranaceus Bunge and their β-glucuronidase inhibitory activity
In this study, a phytochemical characterization of the aerial parts of A. membranaceusled to the isolation of 29 oleanane-type triterpenoid saponins, including 11 new compounds named astraoleanosides E-P (6-9, 13, 14, 18-22), as well as 18 known ones. The structures of these compounds were elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. Among them, astraoleanoside H (9) and cloversaponin III (15) demonstrated the most potent β-glucuronidase inhibitory activities, with IC50 values of 21.20 ± 0.75 and 9.05 ± 0.47 µM, respectively, compared to the positive control d-sa...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Manh Khoa Nguyen Viet Phong Nguyen Seo Young Yang Byung Sun Min Jeong Ah Kim Source Type: research
Novel spiroindoline derivatives targeting aldose reductase against diabetic complications: Bioactivity, cytotoxicity, and molecular modeling studies
Bioorg Chem. 2024 Feb 19;145:107221. doi: 10.1016/j.bioorg.2024.107221. Online ahead of print.ABSTRACTDespite significant developments in therapeutic strategies, Diabetes Mellitus remains an increasing concern, leading to various complications, e.g., cataracts, neuropathy, retinopathy, nephropathy, and several cardiovascular diseases. The polyol pathway, which involves Aldose reductase (AR) as a critical enzyme, has been focused on by many researchers as a target for intervention. On the other hand, spiroindoline-based compounds possess remarkable biological properties. This guided us to synthesize novel spiroindoline oxad...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Özcan Güleç C üneyt Türkeş Mustafa Arslan Yeliz Demir Busra Dincer Abdulilah Ece Ömer İrfan Küfrevioğlu Şükrü Beydemir Source Type: research
Multi-target rational design and synthesis of novel diphenyl-tethered pyrazolopyrimidines targeting EGFR and topoisomerase II with potential DNA intercalation and apoptosis induction
Bioorg Chem. 2024 Feb 17;145:107223. doi: 10.1016/j.bioorg.2024.107223. Online ahead of print.ABSTRACTHerein, we envisioned the design and synthesis of novel pyrazolopyrimidines (confirmed by elemental analysis, 1H and 13C NMR, and mass spectra) as multitarget-directed drug candidates acting as EGFR/TOPO II inhibitors, DNA intercalators, and apoptosis inducers. The target diphenyl-tethered pyrazolopyrimidines were synthesized starting from the reaction of phenyl hydrazine and ethoxymethylenemalononitrile to give aminopyrazole-carbonitrile 2. The latter hydrolysis with NaOH and subsequent reaction with 4-chlorobenzaldhyde a...
Source: Bioorganic Chemistry - February 22, 2024 Category: Chemistry Authors: Ahmed A Gaber Ayman Abo Elmaaty Marwa Sharaky Aliaa A Mosa Abdullah Yahya Abdullah Alzahrani Saad Shaaban Wagdy M Eldehna Ahmed A Al-Karmalawy Source Type: research
