Bioorganic and Medicinal Chemistry Letters This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Discovery of novel oridonin sulfamide derivatives as potent NLRP3 inhibitors by a visible-light photocatalysis-enabled peripheral editing
Bioorg Med Chem Lett. 2024 Feb 1;99:129621. doi: 10.1016/j.bmcl.2024.129621. Epub 2024 Jan 18.ABSTRACTThe progress of organicsyntheticmethod can promote late-stage lead compound modification and novel active compound discovery. Molecular editing technology in the field of organic synthesis, including peripheral and skeletal editing, facilitates rapid access to molecular diversity of a lead compound. Peripheral editing of CH bond activation is gradually used in lead optimization to afford novel active scaffolds and chemical space exploitation. To develop oridonin derivatives with high anti-inflammatory potency, novel oridon...
Source: Bioorganic and Medicinal Chemistry Letters - January 20, 2024 Category: Chemistry Authors: Mochenxuan Li Chuanhao Wang Shuang Ye Wei Li Yanming Zhang Jianyu Yan Yongchuang Wang Hang Yang Yuelin Wu Yongqiang Zhang Huojun Zhang Zhenyuan Miao Source Type: research

Inhibition of dengue viruses by N-methylcytisine thio derivatives through targeting viral envelope protein and NS2B-NS3 protease
This study aimed to expand on the previous research by investigating the antiviral potential of N-methylcytisine thio (mCy thio) derivatives against DENV, understanding the molecular mechanisms of antiviral activity for the active thio derivatives. The inhibitory assays on DENV-2-induced cytopathic effect and infectivity revealed that mCy thio derivatives 3 ((1R,5S)-3-methyl-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocine-8-thione) and 6 ((1S,5R)-3-methyl-2-thioxo-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one) were identified as the active compounds against both DENV-1 and DENV-2. Der...
Source: Bioorganic and Medicinal Chemistry Letters - January 19, 2024 Category: Chemistry Authors: Chen-Sheng Lin Chih-Hao Lu Tsai-Hsiu Lin Yan-Tung Kiu Ju-Ying Kan Yu-Jen Chang Ping-Yi Hung Alena V Koval'skaya Dmitry O Tsypyshev Inna P Tsypysheva Cheng-Wen Lin Source Type: research

Design and synthesis of unique morphinan-type molecules: Their application to the search for the unexplored binding domain between opioid receptors and morphinan ligands
In this study, we found that our novel morphinan-type ligands with a side chain containing a heteroatom positioned above the d-ring have binding affinity for the opioid receptors. These novel skeletons could provide unique templates with the desired side chain above the D-ring in the morphinan skeleton, and thus, potentially advance the SAR studies of morphinan ligands with the opioid receptors.PMID:38228254 | DOI:10.1016/j.bmcl.2024.129611 (Source: Bioorganic and Medicinal Chemistry Letters)
Source: Bioorganic and Medicinal Chemistry Letters - January 16, 2024 Category: Chemistry Authors: Kenta Maeda Tomoya Sugai Akihisa Tokuda Keita Kajino Tsuyoshi Saitoh Hiroshi Nagase Noriki Kutsumura Source Type: research

Synthesis, biological activity evaluation and mechanism of action of novel bis-isatin derivatives as potential anti-liver cancer agents
Bioorg Med Chem Lett. 2024 Feb 1;99:129613. doi: 10.1016/j.bmcl.2024.129613. Epub 2024 Jan 13.ABSTRACTA series of bis-isatin conjugates with lysine linker were synthesized with the aim of probing their antiproliferative potential. All the newly synthesized derivatives (0-100 μM) were first screened against liver cancer cell lines(Huh1, H22, Huh7, Hepa1-6, HepG2, Huh6 and 97H) using CCK-8 assay. Results indicated that the derivative 4d exhibited the most potent activity against Huh1 (IC50 = 17.13 µM) and Huh7(IC50 = 8.265 µM). In vivo anti-tumor study showed that compound 4d effectively inhibited tumor growth in Huh1-ind...
Source: Bioorganic and Medicinal Chemistry Letters - January 15, 2024 Category: Chemistry Authors: Zhifen Li Jingbo Ma Ming Tian Peng Xia Xiannian Lv Rui Hou Yuke Jiang Xiaolong Xu Zhifang Jia Jigang Wang Zhijie Li Source Type: research

Therapeutic potential of Coumarin-polyphenolic acid hybrids in PD: Inhibition of α-Syn aggregation and disaggregation of preformed fibrils, leading to reduced neuronal inclusion formation
This study focuses on the discovery of new potential drugs for treating PD by targeting the aggregation of α-Syn. A series of hybrids combining Coumarin and phenolic acid were designed and synthesized. Four particularly promising compounds were identified, showing strong inhibitory effects with IC50 values ranging from low micromolar to submicromolar concentrations, as low as 0.63 μM. These compounds exhibited a higher binding affinity to α-Syn residues and effectively hindered the entire aggregation process, maintaining the proteostasis conformation of α-Syn and preventing the formation of β-sheet aggregates. This ap...
Source: Bioorganic and Medicinal Chemistry Letters - January 14, 2024 Category: Chemistry Authors: Zhen-Ping Wang Wei Zhang Li-Zi Xing Ya-Dong Zhao Ji Xu Yun-Xiao Zhang Source Type: research

Synthetic assembly of α-O-linked-type GlcNAc using polymer chemistry affords sugar clusters, which effectively bind to lectins
Bioorg Med Chem Lett. 2024 Feb 1;99:129616. doi: 10.1016/j.bmcl.2024.129616. Epub 2024 Jan 10.ABSTRACTFischer's glycoside synthesis was applied to linker precursor alcohols of two different lengths having appropriate alkane chains to obtain the corresponding α-glycoside and it was found to be applicable with moderate yields. Water-soluble glycomonomers were systematically prepared from N-acetyl-d-glucosamine (GlcNAc) by introducing two kinds of alcohols having different methylene lengths. Typical radical polymerizations of the glycomonomers with acrylamide as a modulator for control of the distance between carbohydrate re...
Source: Bioorganic and Medicinal Chemistry Letters - January 12, 2024 Category: Chemistry Authors: Jyuichi Nakada Takahiko Matsushita Tetsuo Koyama Ken Hatano Koji Matsuoka Source Type: research

Design, synthesis and biological evaluation of 6-chloro-quinolin-2-one derivatives as novel FXIa inhibitors
Bioorg Med Chem Lett. 2024 Feb 1;99:129610. doi: 10.1016/j.bmcl.2024.129610. Epub 2024 Jan 9.ABSTRACTA series of 6-chloro-quinolin-2-one derivatives were designed and synthesized as FXIa inhibitors by exploration of P1, P1 prime and P2 prime groups. Each compound was accessed for inhibitory effect on FXIa and some of them were evaluated in the clotting assay. 14c demonstrated excellent in-vitro potency (FXIa IC50: 15 nM, 2 x aPTT: 6.8 μM) and good in-vivo efficacy (prolonged in-vivo aPTT by more than 1-fold but not PT). Moreover, the pharmacokinetics property of 14c were evaluated following intravenous administration in r...
Source: Bioorganic and Medicinal Chemistry Letters - January 11, 2024 Category: Chemistry Authors: Yanshi Wang Jianglin Yuan Sida Yan Peng Liu Zhichao Zheng Shijun Zhang Fancui Meng Wei Liu Changjiang Huang Qunchao Wei Source Type: research

Identification of 4-(6-((2-methoxyphenyl)amino)pyrazin-2-yl)benzoic acids as CSNK2A inhibitors with antiviral activity and improved selectivity over PIM3
We report the synthesis of 2,6-disubstituted pyrazines as potent cell active CSNK2A inhibitors. 4'-Carboxyphenyl was found to be the optimal 2-pyrazine substituent for CSNK2A activity, with little tolerance for additional modification. At the 6-position, modifications of the 6-isopropylaminoindazole substituent were explored to improve selectivity over PIM3 while maintaining potent CSNK2A inhibition. The 6-isopropoxyindole analogue 6c was identified as a nanomolar CSNK2A inhibitor with 30-fold selectivity over PIM3 in cells. Replacement of the 6-isopropoxyindole by isosteric ortho-methoxy anilines, such as 7c, generated an...
Source: Bioorganic and Medicinal Chemistry Letters - January 10, 2024 Category: Chemistry Authors: Kareem A Galal Andreas Kr ämer Benjamin G Strickland Jeffery L Smith Rebekah J Dickmander Nathaniel J Moorman Timothy M Willson Source Type: research

Single step synthesis of β- and γ- aryl-substituted ß- and γ-amino acid derivatives by electrochemistry
Bioorg Med Chem Lett. 2024 Jan 9;100:129614. doi: 10.1016/j.bmcl.2024.129614. Online ahead of print.ABSTRACTElectrochemical transformations are a subject of increasing interest in early drug discovery due to its ability to assemble complex scaffolds under rather mild reaction conditions. In this context, we became interested in electrochemical decarboxylative cross-coupling (DCC) protocols of redox-active esters (RAEs) and halo(hetero)arenes. Starting with the one-step electrochemical synthesis of novel methylamino-substituted heterocycles we recognized the potential of this methodology to deliver a novel approach to β- a...
Source: Bioorganic and Medicinal Chemistry Letters - January 10, 2024 Category: Chemistry Authors: Barbara Pavlovic Christoph Heubel Michael Kurz Elisabeth Oehl Siegfried R Waldvogel Maria M éndez Sven Ruf Source Type: research

Design, synthesis, and evaluation of dual EGFR/AURKB inhibitors as anticancer agents for non-small cell lung cancer
Bioorg Med Chem Lett. 2024 Jan 8;100:129612. doi: 10.1016/j.bmcl.2024.129612. Online ahead of print.ABSTRACTThe epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are first-line agents for mutant EGFR-positive (mEGFR+) NSCLC. However, secondary resistant mutations develop following therapy that prevent EGFR-TKI binding. The EGFR-TKIs are rendered ineffective in NSCLC expressing EGFR resistant mutations (rmEGFR+). Mutations in Kirsten rat sarcoma virus protein (mKRAS) support persistent signaling downstream of EGFR regardless of EGFR-TKI earlier in the signaling cascade. The EGFR-TKIs are ineffective in...
Source: Bioorganic and Medicinal Chemistry Letters - January 10, 2024 Category: Chemistry Authors: Sonali Kurup Dayna Gesinski Kaitlin Assaad Aidan Reynolds Source Type: research

Improved synthesis and evaluation of preclinical pharmacodynamic parameters of a new monocyclic β-lactam DPI-2016
Bioorg Med Chem Lett. 2024 Feb 1;99:129615. doi: 10.1016/j.bmcl.2024.129615. Epub 2024 Jan 8.ABSTRACTMonocyclic β-lactams are stable to a number of β-lactamases and are the focus of researchers for the development of antibacterial drugs, particularly against Enterobacterales. We recently synthesized and reported the bactericidal activity of diverse series of aztreonam appended with amidine moieties as siderophores. One of the derivatives exhibiting the highest MIC value in vitro was selected for further preclinical studies. The compound DPI-2016 was reassessed for its synthetic routes and methods that were improved to fi...
Source: Bioorganic and Medicinal Chemistry Letters - January 10, 2024 Category: Chemistry Authors: Lijuan Zhai Jian Sun Jingwen Ji Lili He Pengjuan Zhou Dong Tang Jinbo Ji Haikang Yang Zafar Iqbal Zhixiang Yang Source Type: research

Expanded library of novel 2,3-pyrrolidinedione analogues exhibit anti-biofilm activity
Bioorg Med Chem Lett. 2024 Feb 1;99:129609. doi: 10.1016/j.bmcl.2024.129609. Epub 2024 Jan 6.ABSTRACTHerein we report a new library of 2,3-pyrrolidinedione analogues that expands on our previous report on the antimicrobial studies of this heterocyclic scaffold. The novel 2,3-pyrrolidinediones reported herein have been evaluated against S. aureus and methicillin-resistant S. aureus (MRSA) biofilms, and this work constitutes our first report on the antibiofilm properties of this class of compounds. The antibiofilm activity of these 2,3-pyrrolidinediones has been assessed through minimum biofilm eradication concentration (MBE...
Source: Bioorganic and Medicinal Chemistry Letters - January 8, 2024 Category: Chemistry Authors: Minhua Nie M Alejandro Valdes-Pena Bram H Frohock Emma Smits Jennifer C Daiker Jessica M Gilbertie Lauren V Schnabel Joshua G Pierce Source Type: research

Expanded Library of Novel 2,3-Pyrrolidinedione Analogues Exhibit Anti-biofilm Activity
Bioorg Med Chem Lett. 2024 Jan 6:129609. doi: 10.1016/j.bmcl.2024.129609. Online ahead of print.ABSTRACTHerein we report a new library of 2,3-pyrrolidinedione analogues that expands on our previous report on the antimicrobial studies of this heterocyclic scaffold. The novel 2,3-pyrrolidinediones reported herein have been evaluated against S. aureus and methicillin-resistant S. aureus (MRSA) biofilms, and this work constitutes our first report on the antibiofilm properties of this class of compounds. The antibiofilm activity of these 2,3-pyrrolidinediones has been assessed through minimum biofilm eradication concentration (...
Source: Bioorganic and Medicinal Chemistry Letters - January 8, 2024 Category: Chemistry Authors: Minhua Nie M Alejandro Valdes-Pena Bram H Frohock Emma Smits Jennifer C Daiker Jessica M Gilbertie Lauren V Schnabel Joshua G Pierce Source Type: research

Design of cyclic peptides as novel inhibitors of ICOS/ICOSL interaction
Bioorg Med Chem Lett. 2024 Jan 5:129599. doi: 10.1016/j.bmcl.2024.129599. Online ahead of print.ABSTRACTCompared to small molecules and antibodies, cyclic peptides exhibit unique biochemical and therapeutic attributes in the realm of pharmaceutical applications. The interaction between the inducible costimulator (ICOS) and its ligand (ICOSL) plays a key role in T-cell differentiation and activation. ICOS/ICOSL inhibition results in a reduction in the promotion of immunosuppressive regulatory T cells (Tregs) in both hematologic malignancies and solid tumors. Herein, we implement the computational cPEPmatch approach to desig...
Source: Bioorganic and Medicinal Chemistry Letters - January 7, 2024 Category: Chemistry Authors: Somaya A Abdel-Rahman Brianda L Santini Laura Calvo-Barreiro Martin Zacharias Moustafa Gabr Source Type: research

Design of cyclic peptides as novel inhibitors of ICOS/ICOSL interaction
Bioorg Med Chem Lett. 2024 Jan 5:129599. doi: 10.1016/j.bmcl.2024.129599. Online ahead of print.ABSTRACTCompared to small molecules and antibodies, cyclic peptides exhibit unique biochemical and therapeutic attributes in the realm of pharmaceutical applications. The interaction between the inducible costimulator (ICOS) and its ligand (ICOSL) plays a key role in T-cell differentiation and activation. ICOS/ICOSL inhibition results in a reduction in the promotion of immunosuppressive regulatory T cells (Tregs) in both hematologic malignancies and solid tumors. Herein, we implement the computational cPEPmatch approach to desig...
Source: Bioorganic and Medicinal Chemistry Letters - January 7, 2024 Category: Chemistry Authors: Somaya A Abdel-Rahman Brianda L Santini Laura Calvo-Barreiro Martin Zacharias Moustafa Gabr Source Type: research