Bibenzyl and naphthalene derivatives from Dendrobium chrysanthum and their anti-hepatic-steatosis activities
In this study, 16 new compounds, six bibenzyls (1-6) and 10 naphthalenes (7-13), including three pairs of naphthalene enantiomers and three known compounds (14-16), were isolated from Dendrobium chrysanthum. Structurally, compounds 1-5 are previously undescribed dimeric bibenzyls, uniquely linked by unusual carbon bonds. The structures of the compounds were determined using spectroscopy and X-ray crystallography. The screening results indicated that 1, 2, and 5 showed remarkable lipid-lowering activities in FFA-induced HepG2 cells, with EC50 values ranging from 3.13 to 6.57 μM. Moreover, 1, 2, and 5 significantly decrease...
Source: Bioorganic Chemistry - February 25, 2024 Category: Chemistry Authors: Zi-Mo Zhang Jin-Ming Chen Xiao-Xia Wang Ling-Yun Wang Shuai Liu Jing Wang Ya-Nan Wang Peng-Yu Zhuang Lu-Lu Wang Hang Liu Source Type: research
Green synthesis of zinc oxide nanoparticles using ethanolic extract of Gliricidia sepium (Jacq.) kunth. Ex. Walp., stem: Characterizations and their gastroprotective effect on ethanol-induced gastritis in rats
This study aims to investigate the potential gastroprotective activity of GSS ZnONPs against gastritis.PMID:38402797 | DOI:10.1016/j.bioorg.2024.107225 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - February 25, 2024 Category: Chemistry Authors: Aya A Wafaey Seham S El-Hawary Mohamed F Abdelhameed Mohamed A El Raey Sahar S Abdelrahman Alaa M Ali Farid N Kirollos Source Type: research
Structural optimization and biological evaluation of ML364 based derivatives as USP2a inhibitors
In conclusion, compound 8v has been identified as a potent USP2a inhibitor with substantial potential for cancer therapy.PMID:38401359 | DOI:10.1016/j.bioorg.2024.107222 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - February 24, 2024 Category: Chemistry Authors: Youngchai Son Ji Su Yang Sang Chul Shin Seo Kyoung Park Yeojin Kim Jinyoung Park Jinha Yu Source Type: research
Hybrid pharmacophore design and synthesis of donepezil-inspired aurone derivative salts as multifunctional acetylcholinesterase inhibitors
The objective of this study was to design and synthesize valuable agents derived from flavonoids for relieving the symptoms of AD. A variety of flavonoid derivative salts incorporating benzylpyridinium units were synthesized and several of them remarkedly inhibited acetylcholinesterase (AChE) activity in vitro. Additionally, aurone derivative salts protected against cell death resulting from t-BHP exposure in rat pheochromocytoma PC12 cells and slightly promoted neurite outgrowth. Furthermore, they potently suppressed the aggregation of amyloid-β (Aβ1-42). Our findings highlight the effectiveness of donepezil-inspired au...
Source: Bioorganic Chemistry - February 24, 2024 Category: Chemistry Authors: Rei Funahashi Fumiaki Matsuura Masayuki Ninomiya Sayo Okabe Shigeo Takashima Kaori Tanaka Atsuyoshi Nishina Mamoru Koketsu Source Type: research
Synthesis and bio-evaluation of newer dihydropyridines and tetrahydropyridines based glycomimetic azasugars
This study presents the synthesis and bio-evaluation of new triazolylated dihydropyridine and tetrahydropyridine azasugar scaffolds (F1-14). Azasugar glycomimetics are the synthetic substances that mimic the structural and functional characteristics of natural carbohydrates showcasing promising potential as therapeutic agents for diabetes. The α-glucosidase inhibitory activity of synthesized final compounds were evaluated against the commercially available α-glucosidase enzyme. Majority of the screened compounds displayed excellent inhibition with IC50 values ranging from 2.12 to 75.11 μM, when compared to the standard ...
Source: Bioorganic Chemistry - February 24, 2024 Category: Chemistry Authors: Nidhi Deswal Priya Takkar Lajpreet Kaur Himanshu Ojha Rakesh Kumar Source Type: research
Glycomimetic inhibitors of tandem-repeat galectins: Simple and efficient
Bioorg Chem. 2024 Feb 20;145:107231. doi: 10.1016/j.bioorg.2024.107231. Online ahead of print.ABSTRACTThe binding of human galectins by glycomimetic inhibitors is a promising therapeutic approach. The structurally distinct group of tandem-repeat galectins has scarcely been studied so far, and there is hardly any knowledge on their ligand specificity or their inhibitory potential, particularly concerning non-natural carbohydrates. Here, we present the synthesis of a library of seven 3-O-disubstituted thiodigalactoside-derived glycomimetics and their affinity to two tandem-repeat galectins, Gal-8 and Gal-9. The straightforwa...
Source: Bioorganic Chemistry - February 23, 2024 Category: Chemistry Authors: David Vrbata Jakub Červený Natalia Kulik Michaela Hovorkov á So ňa Balogová Milu še Vlachová Helena Pelantov á Vladim ír Křen Pavla Bojarov á Source Type: research
Discovery of a doublecortin-like kinase 1 inhibitor to prevent inflammatory responses in acute lung injury
In this study, we designed and synthesized a series of NVP-TAE684-based derivatives as novel anti-inflammatory agents targeting DCLK1. Bio-layer interferometry binding screening and kinase assays of the NVP-TAE684 derivatives led to the discovery of an effective DCLK1 inhibitor (a24), with an IC50 of 179.7 nM. Compound a24 effectively inhibited lipopolysaccharide (LPS)-induced inflammation in macrophages with higher potency than the lead compound. Mechanistically, compound a24 inhibited LPS-induced inflammation by inhibiting DCLK1-mediated IKKβ phosphorylation. Furthermore, compound a24 showed in vivo anti-inflammatory ac...
Source: Bioorganic Chemistry - February 23, 2024 Category: Chemistry Authors: Binhao Cai Ying Xu Ruixiang Luo Kongqin Lu Yuhan Wang Lei Zheng Yawen Zhang Lina Yin Linglan Tu Wu Luo Lulu Zheng Fengzhi Zhang Xinting Lv Qidong Tang Guang Liang Lingfeng Chen Source Type: research
Glycomimetic inhibitors of tandem-repeat galectins: Simple and efficient
Bioorg Chem. 2024 Feb 20;145:107231. doi: 10.1016/j.bioorg.2024.107231. Online ahead of print.ABSTRACTThe binding of human galectins by glycomimetic inhibitors is a promising therapeutic approach. The structurally distinct group of tandem-repeat galectins has scarcely been studied so far, and there is hardly any knowledge on their ligand specificity or their inhibitory potential, particularly concerning non-natural carbohydrates. Here, we present the synthesis of a library of seven 3-O-disubstituted thiodigalactoside-derived glycomimetics and their affinity to two tandem-repeat galectins, Gal-8 and Gal-9. The straightforwa...
Source: Bioorganic Chemistry - February 23, 2024 Category: Chemistry Authors: David Vrbata Jakub Červený Natalia Kulik Michaela Hovorkov á So ňa Balogová Milu še Vlachová Helena Pelantov á Vladim ír Křen Pavla Bojarov á Source Type: research
Discovery of a doublecortin-like kinase 1 inhibitor to prevent inflammatory responses in acute lung injury
In this study, we designed and synthesized a series of NVP-TAE684-based derivatives as novel anti-inflammatory agents targeting DCLK1. Bio-layer interferometry binding screening and kinase assays of the NVP-TAE684 derivatives led to the discovery of an effective DCLK1 inhibitor (a24), with an IC50 of 179.7 nM. Compound a24 effectively inhibited lipopolysaccharide (LPS)-induced inflammation in macrophages with higher potency than the lead compound. Mechanistically, compound a24 inhibited LPS-induced inflammation by inhibiting DCLK1-mediated IKKβ phosphorylation. Furthermore, compound a24 showed in vivo anti-inflammatory ac...
Source: Bioorganic Chemistry - February 23, 2024 Category: Chemistry Authors: Binhao Cai Ying Xu Ruixiang Luo Kongqin Lu Yuhan Wang Lei Zheng Yawen Zhang Lina Yin Linglan Tu Wu Luo Lulu Zheng Fengzhi Zhang Xinting Lv Qidong Tang Guang Liang Lingfeng Chen 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
