New aryl-/heteroarylpiperazine derivatives of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0 < sup > 2,6 < /sup > ]dec-8-ene-3,5,10-trione: Synthesis and preliminary studies of biological activities
Bioorg Med Chem. 2023 Nov 7;96:117518. doi: 10.1016/j.bmc.2023.117518. Online ahead of print.ABSTRACTCompounds containing dicarboximide skeleton such as succinimides, maleimides, glutarimides, and phthalimides possess broad biological properties including anti-fungal, antibacterial, antidepressant, or analgesic activities. The piperazine ring is found in a wide range of molecules that have demonstrated a variety of biological functions such as anticancer action and 5-HT receptors agonist/antagonist activity. In the present study, we combined both structures to develop new antitumor agents, a series of piperazine derivative...
Source: Bioorganic and Medicinal Chemistry - November 11, 2023 Category: Chemistry Authors: Mariola Napi órkowska Dagmara Kurpios-Piec Ewelina Kiernozek-Kali ńska Anna Le śniak Ma łgorzata Klawikowska Magdalena Bujalska-Zadro żny Source Type: research
Target discovery of bioactive natural products with native-compound-coupled CNBr-activated Sepharose 4B beads (NCCB): Applications, mechanisms and outlooks
Bioorg Med Chem. 2023 Sep 26;96:117483. doi: 10.1016/j.bmc.2023.117483. Online ahead of print.ABSTRACTNatural products (NPs) represent a treasure trove for drug discovery and development due to their chemical structural diversity and a broad spectrum of biological activities. Uncovering the biological targets and understanding their molecular mechanism of actions are crucial steps in the development of clinical therapeutics. However, the structural complexity of NPs and intricate nature of biological system present formidable challenges in target identification of NPs. Although significant advances have been made in the de...
Source: Bioorganic and Medicinal Chemistry - November 11, 2023 Category: Chemistry Authors: Yueteng Zhang Junjie Zhang Menglong Li Yan Qiao Wei Wang Lu Ma Kangdong Liu Source Type: research
Structure-guided design and synthesis of ATP-competitive N-acyl-substituted sulfamide d-alanine-d-alanine ligase inhibitors
Bioorg Med Chem. 2023 Oct 26;96:117509. doi: 10.1016/j.bmc.2023.117509. Online ahead of print.ABSTRACTd-Alanine-d-alanine ligase (Ddl) catalyses the ATP-dependent formation of d-Ala-d-Ala, a critical component in bacterial cell wall biosynthesis and is a validated target for new antimicrobial agents. Here, we describe the structure-guided design, synthesis, and evaluation of ATP-competitive N-acyl-substituted sulfamides 27-36, 42, 46, 47 as inhibitors of Staphylococcus aureus Ddl (SaDdl). A crystal structure of SaDdl complexed with ATP and d-Ala-d-Ala (PDB: 7U9K) identified ATP-mimetic 8 as an initial scaffold for further ...
Source: Bioorganic and Medicinal Chemistry - November 10, 2023 Category: Chemistry Authors: Rouven Becker Jordan L Pederick Edward G Dawes John B Bruning Andrew D Abell Source Type: research
Discovery of a new dihydroeugenol-chalcone hybrid with cytotoxic and anti-migratory potential: A dual-action hit for cancer therapeutics
Bioorg Med Chem. 2023 Nov 3;96:117516. doi: 10.1016/j.bmc.2023.117516. Online ahead of print.ABSTRACTCancer still represents a serious public health problem and one of the main problems related to the worsening of this disease is the ability of some tumors to develop metastasis. In this work, we synthesized a new series of chalcones and isoxazoles derived from eugenol and analogues as molecular hybrids and these compounds were evaluated against different tumor cell lines. This structural pattern was designed considering the cytotoxic potential already known for eugenol, chalcones and isoxazoles. Notably, chalcones 7, 9, 10...
Source: Bioorganic and Medicinal Chemistry - November 9, 2023 Category: Chemistry Authors: Izadora Amaral Nakao Tamires Cunha Almeida Adriana Cotta Cardoso Reis Gabrielly Guimar ães Coutinho Aline Mol Hermenegildo Cleydson Finotti Cordeiro Glenda Nicioli da Silva Danielle Ferreira Dias Geraldo C élio Brandão Saulo Fehelberg Pinto Braga Thiag Source Type: research
Discovery of novel dual Bruton's tyrosine kinase (BTK) and Janus kinase 3 (JAK3) inhibitors as a promising strategy for rheumatoid arthritis
We reported the discovery of dual BTK/JAK3 inhibitors which are based on the structure of BTK inhibitor ibrutinib via the method of bioisosterism and computer-aided drug design) Most of the target compounds exhibited moderate to strong inhibitory activities against BTK and JAK3. Among them, compound XL-12 stood out as the most promising candidate targeting BTK and JAK3 with potent inhibitory activities (IC50 = 2.0 nM and IC50 = 14.0 nM respectively). In the in vivo studies, compound XL-12 (40 mg/kg) exhibited more potent antiarthritic activity than ibrutinib (10 mg/kg) in adjuvant arthritis (AA) rat model. Furthermore, com...
Source: Bioorganic and Medicinal Chemistry - November 9, 2023 Category: Chemistry Authors: Tingting Liang Lifang Cen Junjie Wang Ming Cheng Weibo Guo Wenjie Wang Chunqiu Yu Haifeng Zhang Yuan Wang Zhongyan Hao Jiaming Jin Yaoyao Wu Teng Jiang Qihua Zhu Yungen Xu Source Type: research
