Structural modification of natural axinelline A: Achieving reduced colitis side effects through balanced COX inhibition
This study was to discover novel COX inhibitors with balanced inhibition, aiming to mitigate the severe adverse effects through further structural modification of axinelline A. Of the synthetic derivatives, compound 5e showed highest COX-2 inhibitory activity and balanced COX inhibition (IC50 = 1.74 µM; selectivity ((IC50 (COX-1)/IC50(COX-2) = 16.32). The in vitro anti-inflammatory results indicated that 5e effectively suppressed the expression of pro-inflammatory mediators via the NF-κB signaling pathway rather than the MAPK signaling pathway. The in vivo ulcerative colitis assay demonstrated 5e significantly ameliorate...
Source: Bioorganic Chemistry - February 18, 2024 Category: Chemistry Authors: Zhiran Ju Ziyi Shang Yonghong Liu Shihai Xu Jingjie Fang Fener Chen Source Type: research
Proteasome activation: A novel strategy for targeting undruggable intrinsically disordered proteins
Bioorg Chem. 2024 Feb 16;145:107217. doi: 10.1016/j.bioorg.2024.107217. Online ahead of print.ABSTRACTIntrinsically disordered proteins (IDPs) are characterized by their inability to adopt well-defined tertiary structures under physiological conditions. Nonetheless, they often play pivotal roles in the progression of various diseases, including cancer, neurodegenerative disorders, and cardiovascular ailments. Owing to their inherent dynamism, conventional drug design approaches based on structural considerations encounter substantial challenges when applied to IDPs. Consequently, the pursuit of therapeutic interventions di...
Source: Bioorganic Chemistry - February 18, 2024 Category: Chemistry Authors: Qian Yu Zheng Wang Yutong Tu Yu Cao Huajian Zhu Jiaan Shao Rangxiao Zhuang Yubo Zhou Jiankang Zhang Source Type: research
Design, synthesis, and biological evaluation of some new 2-phenyl-3,6-pyridazinedione derivatives as PDE-5 inhibitors
Bioorg Chem. 2024 Feb 16;145:107213. doi: 10.1016/j.bioorg.2024.107213. Online ahead of print.ABSTRACTVarious 2-phenyl-3,6-pyridazinedione derivatives 4a-j, 5a-c, 6a,b, 7a-c, 8, 9, 10a-d, and 11a-d, were effectivelysynthesized, and tested for their potential inhibition of phosphodiesterase enzyme at 10 µM. Then fourteen compounds exhibiting the highest inhibition 4b, 4d, 4e, 4g, 4h, 4i, 5a, 6a,b, 7c, 10a,b, 11a, and 11d were selected for screening their PDE-5 inhibition, where compounds 4b,g,h, and 11a revealed promising PDE-5 inhibition having IC50 values = 25, 53, 22, and 42 nM, respectively in comparison with Sildenafi...
Source: Bioorganic Chemistry - February 18, 2024 Category: Chemistry Authors: Zeinab S Abd-Rabo Riham F George Dalia K Zaafar Aya Y Gawish Aya M Serry Source Type: research
Structural modification of natural axinelline A: Achieving reduced colitis side effects through balanced COX inhibition
This study was to discover novel COX inhibitors with balanced inhibition, aiming to mitigate the severe adverse effects through further structural modification of axinelline A. Of the synthetic derivatives, compound 5e showed highest COX-2 inhibitory activity and balanced COX inhibition (IC50 = 1.74 µM; selectivity ((IC50 (COX-1)/IC50(COX-2) = 16.32). The in vitro anti-inflammatory results indicated that 5e effectively suppressed the expression of pro-inflammatory mediators via the NF-κB signaling pathway rather than the MAPK signaling pathway. The in vivo ulcerative colitis assay demonstrated 5e significantly ameliorate...
Source: Bioorganic Chemistry - February 18, 2024 Category: Chemistry Authors: Zhiran Ju Ziyi Shang Yonghong Liu Shihai Xu Jingjie Fang Fener Chen Source Type: research
Proteasome activation: A novel strategy for targeting undruggable intrinsically disordered proteins
Bioorg Chem. 2024 Feb 16;145:107217. doi: 10.1016/j.bioorg.2024.107217. Online ahead of print.ABSTRACTIntrinsically disordered proteins (IDPs) are characterized by their inability to adopt well-defined tertiary structures under physiological conditions. Nonetheless, they often play pivotal roles in the progression of various diseases, including cancer, neurodegenerative disorders, and cardiovascular ailments. Owing to their inherent dynamism, conventional drug design approaches based on structural considerations encounter substantial challenges when applied to IDPs. Consequently, the pursuit of therapeutic interventions di...
Source: Bioorganic Chemistry - February 18, 2024 Category: Chemistry Authors: Qian Yu Zheng Wang Yutong Tu Yu Cao Huajian Zhu Jiaan Shao Rangxiao Zhuang Yubo Zhou Jiankang Zhang Source Type: research
Design, synthesis, and biological evaluation of some new 2-phenyl-3,6-pyridazinedione derivatives as PDE-5 inhibitors
Bioorg Chem. 2024 Feb 16;145:107213. doi: 10.1016/j.bioorg.2024.107213. Online ahead of print.ABSTRACTVarious 2-phenyl-3,6-pyridazinedione derivatives 4a-j, 5a-c, 6a,b, 7a-c, 8, 9, 10a-d, and 11a-d, were effectivelysynthesized, and tested for their potential inhibition of phosphodiesterase enzyme at 10 µM. Then fourteen compounds exhibiting the highest inhibition 4b, 4d, 4e, 4g, 4h, 4i, 5a, 6a,b, 7c, 10a,b, 11a, and 11d were selected for screening their PDE-5 inhibition, where compounds 4b,g,h, and 11a revealed promising PDE-5 inhibition having IC50 values = 25, 53, 22, and 42 nM, respectively in comparison with Sildenafi...
Source: Bioorganic Chemistry - February 18, 2024 Category: Chemistry Authors: Zeinab S Abd-Rabo Riham F George Dalia K Zaafar Aya Y Gawish Aya M Serry Source Type: research
Effects of selenium nanoparticles produced by Lactobacillus acidophilus HN23 on lipid deposition in WRL68 cells
In conclusion, SeNPs produced by probiotics L. acidophilus had the potential to alleviate NAFLD by reducing hepatocyte lipid deposition and oxidative damage. This study may open a new avenue for SeNPs drug development to treat NAFLD.PMID:38367427 | DOI:10.1016/j.bioorg.2024.107165 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - February 17, 2024 Category: Chemistry Authors: Xianglan Lei Yuxuan Peng Yan Li Qianyuan Chen Zhenguo Shen Wen Yin Viktar Lemiasheuski Siyang Xu Jin He Source Type: research
Counterion influence on near-infrared-II heptamethine cyanine salts for photothermal therapy
Bioorg Chem. 2024 Feb 13;145:107206. doi: 10.1016/j.bioorg.2024.107206. Online ahead of print.ABSTRACTPhotothermal therapy (PTT) has attracted extensive attention in cancer treatment. Heptamethine cyanine dyes with near-infrared (NIR) absorption performance have been investigated for PTT. However, they are often accompanied by poor photostability, suboptimal photothermal conversion and limited therapeutic efficacy. The photophysical properties of fluorescent organic salts can be tuned through counterion pairing. However, whether the counterion can influence the photostability and photothermal properties of heptamethine cya...
Source: Bioorganic Chemistry - February 17, 2024 Category: Chemistry Authors: Yilin Zheng Tingyan Chen Yu Gao Haijun Chen Source Type: research
Diterpenoids from Euphorbia peplus possessing cytotoxic and anti-inflammatory activities
Bioorg Chem. 2024 Feb 13;145:107194. doi: 10.1016/j.bioorg.2024.107194. Online ahead of print.ABSTRACTPhytochemical investigation into the medium polar fraction of the ethanol extract of Euphorbia peplus led to the identification of 32 diterpenoids with five structural types. Compounds 1-5 and 7-11 are reported for the first time, while the configuration of 6,7-epoxy group of 6 was revised to be β-oriented. Compounds 1-5 feature a rare structural variation of the double bond at Δ1 migrating to Δ1(10) in the tigliane-type diterpenoid family. Biologically, compound 21 was found to be the only one to show moderate cytotoxi...
Source: Bioorganic Chemistry - February 17, 2024 Category: Chemistry Authors: Ying Li Zhi-Pu Yu Yu-Peng Li Jin-Hai Yu Jian-Min Yue Source Type: research
The first-in-class pyrazole-based dual InhA-VEGFR inhibitors towards integrated antitubercular host-directed therapy
Bioorg Chem. 2024 Feb 8;145:107179. doi: 10.1016/j.bioorg.2024.107179. Online ahead of print.ABSTRACTSeveral facets of the host response to tuberculosis have been tapped for clinical investigation, especially targeting angiogenesis mediated by VEGF signaling from infected macrophages. Herein, we rationalized combining the antiangiogenic effects of VEGFR-2 blockade with direct antitubercular InhA inhibition in single hybrid dual inhibitors as advantageous alternatives to the multidrug regimens. Inspired by expanded triclosans, the ether ligation of triclosan was replaced by rationalized linkers to assemble the VEGFR-2 inhib...
Source: Bioorganic Chemistry - February 17, 2024 Category: Chemistry Authors: Marwa M Shaaban Mohamed Teleb Hanan M Ragab Monica Singh Bassma H Elwakil Lamia A Heikal D Sriram Mona A Mahran Source Type: research
The binding selectivity of quercetin and its structure-related polyphenols to human serum albumin using a fluorescent dye cocktail for multiplex drug-site mapping
In this report, the binding selectivity and strength of interactions to HSA-binding sites (sites I or II) by flavonoids were evaluated using competition experiments and the specific fluorescent dyes, dansylamide and BD140. Most tested flavonoids bound site I preferentially, with the binding strength dependent on the mother structure in the order flavonol > flavone > flavanone > flavan 3-ols. Glycosylation or glucuronidation reduced the binding of quercetin to site I of HSA, whereas sulfation increased binding. Quercetin 7-sulfate showed the strongest binding and molecular docking simulations supported this observa...
Source: Bioorganic Chemistry - February 16, 2024 Category: Chemistry Authors: Rie Mukai Hitomi Okuyama Miku Uchimura Kozue Sakao Miyu Matsuhiro Mayumi Ikeda-Imafuku Yu Ishima Miyu Nishikawa Shinichi Ikushiro Akihiro Tai Source Type: research
Novel multi-target angiogenesis inhibitors as potential anticancer agents: Design, synthesis and preliminary activity evaluation
Bioorg Chem. 2024 Feb 14;145:107211. doi: 10.1016/j.bioorg.2024.107211. Online ahead of print.ABSTRACTBased on the crucial role of histone deacetylase (HDAC) and receptor tyrosine kinase in angiogenesis, in situ assembly, skeletal transition, molecular hybridization, and pharmacophore fusion were employed to yield seventy-six multi-target angiogenesis inhibitors. Biological evaluation indicated that most of the compounds exhibited potent proliferation inhibitory activity on MCF-7 cells, with the TH series having the highest inhibitory activity on MCF-7 cells. In addition, the IC50 values of TA11 and TH3 against HT-29 cells...
Source: Bioorganic Chemistry - February 16, 2024 Category: Chemistry Authors: Qingqing Zhang Zilong Li Junyu Zhang Yanchen Li Xiaoyan Pan Jingkun Qu Jie Zhang Source Type: research
Triphenylphosphonium-linked derivative of hecogenin with enhanced antiproliferative activity: Design, synthesis, and biological evaluation
In this study, we incorporated triphenylphosphonium cation (TPP+) at the C-3 and C-12 positions through different lengths of alkyl chains to target mitochondria and enhance the efficacy and selectivity of the parent compound. Cytotoxicity screening revealed that most of the target compounds exhibited potent antiproliferative activity against five human cancer cell lines (MKN45, A549, HCT-116, MCF-7, and HepG2). Structure-activity relationship studies indicated that the TPP+ group significantly enhanced the antiproliferative potency of HCG. Among these compounds, 3c demonstrated remarkable potency against MKN45 cells with a...
Source: Bioorganic Chemistry - February 16, 2024 Category: Chemistry Authors: Jinling Zhang Wenquan Zhu Yukun Ma Xiaoying Huang Wenle Su Yu Sun Qi Liu Tiancheng Ma Liwei Ma Jia Sun Songjie Fan Xiaoli Wang Song Lin Wenbao Wang Cuiyan Han Source Type: research
The binding selectivity of quercetin and its structure-related polyphenols to human serum albumin using a fluorescent dye cocktail for multiplex drug-site mapping
In this report, the binding selectivity and strength of interactions to HSA-binding sites (sites I or II) by flavonoids were evaluated using competition experiments and the specific fluorescent dyes, dansylamide and BD140. Most tested flavonoids bound site I preferentially, with the binding strength dependent on the mother structure in the order flavonol > flavone > flavanone > flavan 3-ols. Glycosylation or glucuronidation reduced the binding of quercetin to site I of HSA, whereas sulfation increased binding. Quercetin 7-sulfate showed the strongest binding and molecular docking simulations supported this observa...
Source: Bioorganic Chemistry - February 16, 2024 Category: Chemistry Authors: Rie Mukai Hitomi Okuyama Miku Uchimura Kozue Sakao Miyu Matsuhiro Mayumi Ikeda-Imafuku Yu Ishima Miyu Nishikawa Shinichi Ikushiro Akihiro Tai Source Type: research
Novel multi-target angiogenesis inhibitors as potential anticancer agents: Design, synthesis and preliminary activity evaluation
Bioorg Chem. 2024 Feb 14;145:107211. doi: 10.1016/j.bioorg.2024.107211. Online ahead of print.ABSTRACTBased on the crucial role of histone deacetylase (HDAC) and receptor tyrosine kinase in angiogenesis, in situ assembly, skeletal transition, molecular hybridization, and pharmacophore fusion were employed to yield seventy-six multi-target angiogenesis inhibitors. Biological evaluation indicated that most of the compounds exhibited potent proliferation inhibitory activity on MCF-7 cells, with the TH series having the highest inhibitory activity on MCF-7 cells. In addition, the IC50 values of TA11 and TH3 against HT-29 cells...
Source: Bioorganic Chemistry - February 16, 2024 Category: Chemistry Authors: Qingqing Zhang Zilong Li Junyu Zhang Yanchen Li Xiaoyan Pan Jingkun Qu Jie Zhang Source Type: research
