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.

Synthesis and initial evaluation of radioiodine-labelled deuterated tropane derivatives targeting dopamine transporter
Bioorg Med Chem Lett. 2024 Feb 24:129678. doi: 10.1016/j.bmcl.2024.129678. Online ahead of print.ABSTRACTThe dopamine transporter (DAT) is closely related to a variety of neurological disorders including Parkinson's disease (PD) and other neurodegenerative diseases. In vivo imaging of DAT with radio-labelled tracers has become a powerful technique in related disorders. The radioiodine-labelled tropane derivative [123I]FP-CIT ([123I]1a) is widely used in clinical single photon emission computed tomography (SPECT) imaging as a DAT imaging agent. To develop more metabolically stable DAT radioligands for accurate imaging, this...
Source: Bioorganic and Medicinal Chemistry Letters - February 26, 2024 Category: Chemistry Authors: Jie Liu Jing Kang Meihui Qi Jie Tang Yi Fang Chunyi Liu Jingjing Hong Jiaojiao Zuo Zhengping Chen Source Type: research

Development of STING degrader with double covalent ligands
In this study, we used a minimal covalent handle recently developed as the ligand portion of an E3 ligase. The engineered STING degrader with a low molecular weight compound covalently binds to STING and E3 ligase. Degrader 2 showed sustained STING degradation activity at lower concentrations (3 µM, 48 h, about 75 % degradation) compared to a reported STING PROTAC, SP23. This discovery holds significance for its potential in treating autoinflammatory and autoimmune diseases, offering promising avenues for developing more efficacious STING-targeted therapies.PMID:38408510 | DOI:10.1016/j.bmcl.2024.129677 (Source: Bioorgani...
Source: Bioorganic and Medicinal Chemistry Letters - February 26, 2024 Category: Chemistry Authors: Miki Nakamura Nobumichi Ohoka Norihito Shibata Takao Inoue Genichiro Tsuji Yosuke Demizu Source Type: research

Development of 1,5-diarylpyrazoles as EGFR/JNK-2 dual inhibitors: design, synthesis, moleecular docking, and bioactivity evaluation
Bioorg Med Chem Lett. 2024 Feb 24;102:129673. doi: 10.1016/j.bmcl.2024.129673. Online ahead of print.ABSTRACTThe eradication of multifactorial diseases, such as cancer, requires the design of drug candidates that attack multiple targets that contribute to the progression and proliferation of such diseases. Here, 1,5-diarylpyrazole derivatives bearing vanillin or sulfanilamide are developed as potential dual inhibitors of epidermal growth factor receptor (EGFR)/c-Jun N-terminal kinase 2 (JNK-2) for possible anticancer activity. These derivatives inhibited the growths of DLD-1, HeLa, K-562, SUIT-2 and HepG2 cancer cell lines...
Source: Bioorganic and Medicinal Chemistry Letters - February 26, 2024 Category: Chemistry Authors: Osama M Soltan Salah A Abdel-Aziz Montaser Sh Shaykoon Keima Osawa Atsushi Narumi Mohamed Abdel-Aziz Mai E Shoman Hiroyuki Konno Source Type: research

Exploration of bromodomain ligand-linker conjugation sites for efficient CBP/p300 heterobifunctional degrader activity
Bioorg Med Chem Lett. 2024 Feb 24:129676. doi: 10.1016/j.bmcl.2024.129676. Online ahead of print.ABSTRACTSynthesis of proteolysis targeting chimeras (PROTACs) involves conjugation of an E3 ligase binding ligand to a ligand targeting a protein of interest via a rigid or flexible chemical linker. The choice of linker conjugation site on these ligands can be informed by structural analysis of ligand-target binding modes, the feasibility of synthetic procedures to access specific sites, and computational modeling of predicted ternary complex formations. Small molecules that target bromodomains - epigenetic readers of lysine ac...
Source: Bioorganic and Medicinal Chemistry Letters - February 26, 2024 Category: Chemistry Authors: Praveen Kumar Tiwari Sai Reddy Doda Raghu Vannam Manish Hudlikar Drew Harrison Samuel Ojeda Sumit Rai Ann-Sophie Koglin Angelique Nguyen Gilbert Christopher J Ott Source Type: research

Fyn, Blk, and Lyn kinase inhibitors: A mini-review on medicinal attributes, research progress, and future insights
Bioorg Med Chem Lett. 2024 Feb 24;102:129674. doi: 10.1016/j.bmcl.2024.129674. Online ahead of print.ABSTRACTFyn, Blk, and Lyn are part of a group of proteins called Src family kinases. They are crucial in controlling cell communication and their response to the growth, changes, and immune system. Blocking these proteins with inhibitors can be a way to treat diseases where these proteins are too active. The primary mode of action of these inhibitors is to inhibit the phosphorylation of Fyn, Blk, and Lyn receptors, which in turn affects how signals pass within the cells. This review shows the structural and functional aspec...
Source: Bioorganic and Medicinal Chemistry Letters - February 26, 2024 Category: Chemistry Authors: Rupali Kohal None Bhavana Preety Kumari Arun Kumar Sharma Ghanshyam Das Gupta Sant Kumar Verma Source Type: research

Development of 1,5-diarylpyrazoles as EGFR/JNK-2 dual inhibitors: design, synthesis, moleecular docking, and bioactivity evaluation
Bioorg Med Chem Lett. 2024 Feb 24:129673. doi: 10.1016/j.bmcl.2024.129673. Online ahead of print.ABSTRACTThe eradication of multifactorial diseases, such as cancer, requires the design of drug candidates that attack multiple targets that contribute to the progression and proliferation of such diseases. Here, 1,5-diarylpyrazole derivatives bearing vanillin or sulfanilamide are developed as potential dual inhibitors of epidermal growth factor receptor (EGFR)/c-Jun N-terminal kinase 2 (JNK-2) for possible anticancer activity. These derivatives inhibited the growths of DLD-1, HeLa, K-562, SUIT-2 and HepG2 cancer cell lines, wi...
Source: Bioorganic and Medicinal Chemistry Letters - February 26, 2024 Category: Chemistry Authors: Osama M Soltan Salah A Abdel-Aziz Montaser Sh Shaykoon Keima Osawa Atsushi Narumi Mohamed Abdel-Aziz Mai E Shoman Hiroyuki Konno Source Type: research

Fyn, Blk, and Lyn kinase inhibitors: A mini-review on medicinal attributes, research progress, and future insights
Bioorg Med Chem Lett. 2024 Feb 24:129674. doi: 10.1016/j.bmcl.2024.129674. Online ahead of print.ABSTRACTFyn, Blk, and Lyn are part of a group of proteins called Src family kinases. They are crucial in controlling cell communication and their response to the growth, changes, and immune system. Blocking these proteins with inhibitors can be a way to treat diseases where these proteins are too active. The primary mode of action of these inhibitors is to inhibit the phosphorylation of Fyn, Blk, and Lyn receptors, which in turn affects how signals pass within the cells. This review shows the structural and functional aspects o...
Source: Bioorganic and Medicinal Chemistry Letters - February 26, 2024 Category: Chemistry Authors: Rupali Kohal None Bhavana Preety Kumari Arun Kumar Sharma Ghanshyam Das Gupta Sant Kumar Verma Source Type: research

Synthesis, antibacterial activity, and 3D-QASR studies of matrine-indole derivatives as potential antibiotics
Bioorg Med Chem Lett. 2024 Feb 20:129671. doi: 10.1016/j.bmcl.2024.129671. Online ahead of print.ABSTRACTMatrine and indole have antibacterial, anticancer, and other biological activities, in order to develop new antibiotics to solve the problem of multi-drug resistant bacteria. In this paper, we synthesized a series of 29 novel matrine derivatives as potential drug candidates by combining indole analogs and matrine. The antibacterial activity of these compounds was evaluated through minimum inhibitory concentration (MIC) assays against five bacterial strains (S. aureus, C. albicans, P. acnes, P. aeruginosa, and E. coli). ...
Source: Bioorganic and Medicinal Chemistry Letters - February 22, 2024 Category: Chemistry Authors: Yufang Li Jamal A H Kowah Meiyan Jiang Yaqing Wu Lisheng Wang Fangfang Yang Source Type: research

Discovery of an ellipticine derivative as TLR3 inhibitor against influenza A virus and SARS-CoV-2
In conclusion, this study demonstrates the potential of SMU-CX1 in inhibiting IAV and SARS-CoV-2 activity, thereby offering a novel approach for designing antiviral drugs against highly pathogenic viruses.PMID:38387691 | DOI:10.1016/j.bmcl.2024.129672 (Source: Bioorganic and Medicinal Chemistry Letters)
Source: Bioorganic and Medicinal Chemistry Letters - February 22, 2024 Category: Chemistry Authors: Yue Pan Qiuyue Fu Yinyan Li Jie Yang Kui Cheng Source Type: research

Re-exploration of tetrahydro- β-carboline scaffold: Discovery of selective histone deacetylase 6 inhibitors with neurite outgrowth-promoting and neuroprotective activities
Bioorg Med Chem Lett. 2024 Feb 21;102:129670. doi: 10.1016/j.bmcl.2024.129670. Online ahead of print.ABSTRACTHistone deacetylase 6 (HDAC6) has drawn more and more attention for its potential application in Alzheimer's disease (AD) therapy. A series of tetrahydro-β-carboline (THβC) hydroxamic acids with aryl linker were synthesized. In enzymatic assay, all compounds exhibited nanomolar IC50 values. The most promising compound 11d preferentially inhibited HDAC6 (IC50, 8.64 nM) with approximately 149-fold selectivity over HDAC1. Molecular simulation revealed that the hydroxamic acid of 11d could bind to the zinc ion by a bi...
Source: Bioorganic and Medicinal Chemistry Letters - February 22, 2024 Category: Chemistry Authors: Wen Wen Jiadong Hu Chenxi Wang Rui Yang Yabo Zhang Baibei Huang Tingting Qiao Jiayun Wang Xin Chen Source Type: research