BIOORGANIC & MEDICINAL CHEMISTRY LETTERS生物有机与药物化学快报
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS(英文缩写 BIOORG MED CHEM LETT),ISSN 0960-894X,eISSN 1464-3405,中文译名:生物有机与药物化学快报 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-27 至 2026-09-27，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 2.940 | Q2 |
| 2022 | 2.700 | Q2 |
| 2023 | 2.500 | Q2 |
| 2024 | 2.200 | Q2 |
| 2025 | 2.300 | Q2 |
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 最新收录文献
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1. Caffeic acid phenethyl ester derivatives inhibit glyoxalase I activity and induce cell death in cultured cancer cell lines.
PMID:日期:2026-12-01Glyoxalase I (GLO I) is the rate-limiting enzyme responsible for the detoxification of methylglyoxal, a toxic byproduct of anaerobic glycolysis. GLO I is highly expressed in various tumors and has therefore been recognized as a promising target for cancer therapy. We previously identified several cis-diol-containing polyphenols, namely, myricetin, delphinidin, and piceatannol, as potent inhibitors of human GLO I, inducing cell death in GLO I-dependent cancer cells. In this study, we examined the inhibitory abilities to GLO I of another cis-diol-containing polyphenol, caffeic acid phenethyl ester (CAPE). CAPE showed potent GLO I inhibitory activity with an IC value of 7.9 ± 1.2 μM and antiproliferative effects on GLO I-dependent cancer cell lines. In contrast, caffeic acid and phenethyl alcohol, the components of CAPE, did not show GLO I inhibitory activity and exerted drastically lower effects on cancer cell proliferation than CAPE. Caffeic acid benzyl ester and phenyl ester possessed similar inhibitory effects as CAPE, whereas methyl ester showed a notably weaker effect than CAPE. We selected nine compounds (CAD-01-CAD-09) in silico using caffeic acid n-butyl ester as a query molecule. Among these compounds, CAD-09 exhibited a sixfold increase in GLO I inhibition than CAPE and showed a statistically significant antiproliferative effect on HL-60 cells. Overall, caffeic acid esters may provide a promising structural framework for the development of GLO I inhibitors with anticancer potential.
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2. Synthesis, computational and in vitro anti-tubercular activity studies of thiadiazole-linked pyridazinone derivatives.
PMID:日期:2026-12-01Mycobacterium tuberculosis (Mtb) is an infectious bacterium that causes pulmonary tuberculosis (TB). The emergence of drug-resistant Mtb strains necessitates the need for the identification of novel antitubercular agents. In this study, we have repurposed pyridazinone-1,3,4-thiadiazole hybrids for their in-vitro antitubercular activity against Mtb. We have designed and synthesised a series of pyridazinone-1,3,4-thiadiazole hybrids (7a-r). Among these, several compounds (especially 7a, 7c, 7d, 7e, 7n, 7p, 7q, and 7r) inhibited Mtb in vitro, while compound 7d showed moderate antimycobacterial activity (MIC 6.25 mM). Further MIC determination against Mycobacterium bovis BCG wild-type and mutant strains revealed that compound 7d does not inhibit known Mtb targets such as InhA, KatG, HadC or MmpL3. The current results do not conclusively identify the molecular target or mechanism of action of compound 7d and the present results do not provide sufficient evidence to differentiate among the proposed targets of compound 7d. In silico studies showed that these compounds complied with Lipinski's rule, promoting favourable drug-like characteristics. These findings suggest that the pyridazinone-1,3,4-thiadiazole hybrid scaffolds can be optimised further to develop novel antitubercular agents.
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3. Design, synthesis, and evaluation of novel 5-aminolevulinic acid and 3-hydroxypyridinone conjugates for enhanced photodynamic therapy in triple-negative breast cancer.
PMID:日期:2026-12-01Triple-negative breast cancer (TNBC) is a highly aggressive malignancy lacking effective targeted therapies. While 5-Aminolevulinic acid (5-ALA) is an FDA-approved prodrug for photodynamic therapy (PDT), its clinical efficacy against TNBC is severely restricted by poor lipophilicity and the rapid metabolic clearance of its active photosensitizer, protoporphyrin IX (PpIX), into heme. To overcome these limitations, we designed and synthesized 28 novel prodrug conjugates by covalently linking 5-ALA with the iron chelator 3-hydroxypyridinone (HPO) via an ester bond, exploring both R and S stereochemical configurations. Biological evaluations revealed that these conjugates possessed significantly improved lipophilicity and negligible dark toxicity, while exhibiting significantly enhanced phototoxicity to free 5-ALA. Notably, the R-configuration conjugates 13a and 13d emerged as the most potent candidates against MDA-MB-231 TNBC cells, demonstrating IC values of 51.16 ± 1.93 μM and 49.65 ± 2.50 μM, respectively (vs. >100 μM for 5-ALA). Mechanistic studies suggested that these conjugates induced nearly 4-fold higher intracellular PpIX fluorescence than 5-ALA, which is hypothesized to correlate with HPO-mediated labile iron chelation and subsequent preservation of the intracellular PpIX pool against ferrochelatase-mediated clearance. These findings highlight the promise of 5-ALA-HPO conjugates as synergistic, dual-action photosensitizers for advancing PDT in aggressive TNBC models in vitro.
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5. Discovery of orally available benzimidazole-based STING antagonists with in vivo activity.
PMID:日期:2026-12-01Stimulator of interferon genes (STING) plays a pivotal role in the innate immune system. However, aberrant activation of the STING pathway has been implicated in the development of autoimmune and inflammatory diseases. Herein, we report the discovery of a series of novel, orally available benzimidazole derivatives as STING antagonists. S-570 (21b) was identified as a potent STING antagonist that covalently binds to Cys91. Oral administration of S-570 in a CMA-induced inflammation mouse model significantly suppressed the production of IFN-β, IL-6, and TNF-α.
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7. Novel salicylamido sulfonamides as CD73 immune checkpoint inhibitors: Synthesis and in vitro biological evaluation.
PMID:日期:2026-12-01The immune checkpoint enzyme CD73 plays a crucial role in the adenosine (ADO) metabolic pathway by catalyzing the conversion of AMP to adenosine. Dysregulated CD73 activity elevates extracellular ADO in the tumor microenvironment, driving immunosuppression and tumor immune evasion, highlighting CD73 as a key immunotherapeutic target. In this study, we report the design and synthesis of a novel series of salicylamido sulfonamide-based small-molecule CD73 inhibitors. The in vitro CD73 inhibitory assay reveals that SA-41 and SA-26 exhibited potent activity with IC values of 2.83 ± 0.45 μM and 2.96 ± 0.46 μM, respectively. Molecular docking and dynamic simulations revealed that SA-26 maintained stable interactions with CD73 throughout a 100-ns simulation with no significant deviation. Furthermore, in silico ADME analysis indicated that both lead compounds possess favourable drug-like properties, with no Lipinski's rule-of-five violations, balanced lipophilicity, and acceptable predicted oral absorption, supporting their pharmacokinetic potential. These findings highlight SA-26 and SA-41 as promising candidates for further development as non- nucleotide-based small-molecule CD73 inhibitors.
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8. Design and synthesis of dual-target CDK9-EZH2 inhibitors using a pharmacophore fusion strategy.
PMID:日期:2026-12-01Cyclin-dependent kinase 9 (CDK9), a key member of the CDK family, plays a crucial role in transcriptional regulation. As its expression is dysregulated in various cancers, CDK9 is regarded as a promising therapeutic target. However, the clinical efficacy of traditional CDK9 inhibitors is limited by potential on-target toxicity, and degradation-based strategies face similar challenges. In recent years, dual-target inhibitors against CDK9 have gradually become a research focus. Our group previously reported a CDK9/EZH2 dual inhibitor, D16, though its activity still required further improvement. Furthermore, to validate the general applicability of this design strategy, we designed a series of new CDK9/EZH2 dual-target inhibitors by conjugating a self-designed CDK9-targeting fragment with a selective EZH2 inhibitor. Among them, compound A9 demonstrated excellent inhibitory activity, with IC values of 19.3 nM in U2932 cells and 9.1 nM in KARPAS-422 cells. Compared to single-target inhibitors, its dual inhibitory action significantly increased the apoptosis rate and induced substantial DNA damage in DLBCL cells.
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9. Toward targeted covalent inhibition of Cruzipain for the treatment of Chagas disease.
PMID:日期:2026-12-01Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), remains a neglected tropical disease with limited therapeutic options. Cruzipain (CZP), the main cysteine protease of T. cruzi, has been extensively validated as a drug target due to its essential roles in parasite biology and pathogenesis. Targeted covalent inhibitors (TCIs) have emerged as a promising strategy to achieve potent and selective CZP inhibition, driven by advances in covalent warhead chemistry and structure-based drug design. However, their rational development faces significant challenges associated with the complex biological features of T. cruzi. In particular, the structural diversity of CZP subtypes and the frequent lack of translation from enzymatic inhibition to trypanocidal activity represent major bottlenecks in the field. This review provides a comprehensive and critical overview of the chemical space explored for CZP TCIs, including both peptidic and non-peptidic scaffolds, as well as the diverse range of covalent warheads employed. We further discuss best practices for biological evaluation of TCIs, emphasizing the importance of integrating structure-kinetics relationships and selectivity profiling. In addition, we highlight the central role of computational approaches in enabling the rational exploration of this complex chemical landscape. By integrating chemical, biological, and computational perspectives, this review delineates key challenges and emerging opportunities in the development of CZP TCIs, providing a framework to improve bioactivity translation and accelerate the discovery of effective antichagasic agents.
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10. Development of karapinchamine A-related carbazoles with antiproliferative activity against glioblastoma-derived cancer stem cells and blood-brain barrier permeability.
PMID:日期:2026-12-01Karapinchamine A (1)-a geranylated carbazole isolated from the leaves of Bergera koenigii (syn. of Murraya koenigii) (curry leaf)-was synthesized together with twelve N-substituted carbazole derivatives. Their antiproliferative activities were evaluated against cancer stem cells (CSCs) derived from the human glioblastoma (GBM) U-251 MG cell line and against GBM cells (non-CSCs). In addition to compound 1, compounds 4 and 5 bearing a hydroxy group on the carbazole scaffold and a geranyl group at the N-position exhibited activity against CSCs, indicating that these functional groups are essential for biological activity. Furthermore, compound 5 showed stronger activity against CSCs (IC = 3.9 μM) than non-CSCs (IC = 19.2 μM), suggesting CSC-selective activity. Moreover, compounds 4 and 5 were found to possess blood-brain barrier (BBB) permeability comparable to that of caffeine. Thus, N-geranylated carbazole derivatives such as compound 5, which exhibit selective antiproliferative activity against CSCs and possess BBB permeability, are attractive pharmaceutical lead compounds for the treatment of GBM.