Bioorganic and Medicinal Chemistry Letters 
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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.In vitro inhibition of α-Synuclein aggregation and disaggregation of preformed fibers by polyphenol hybrids with 2-conjugated benzothiazole
In this study, a series of benzothiazole-polyphenol hybrids was designed and synthesized. Three identified compounds exhibited notable inhibitory activities against α-Syn aggregation in vitro, with IC50 values in the low micromolar range. These inhibitors demonstrated sustained inhibitory effects throughout the entire aggregation process, stabilizing α-Syn proteostasis conformation. Moreover, the compounds effectively disintegrated preformed α-Syn oligomers and fibers, potentially by binding to specific domains within the fibers, inducing fibril instability, collapse, and ultimately resulting in smaller-sized aggregates...
Source: Bioorganic and Medicinal Chemistry Letters - April 17, 2024 Category: Chemistry Authors: Ya-Dong Zhao Wei Zhang Li-Zi Xing Ji Xu Wei-Min Shi Yun-Xiao Zhang Source Type: research
Inhibition of kynurenine production by N,O-substituted hydroxylamine derivatives
In this study, an amino acid derivative, compound 1 was discovered using a cell-based assay with our screening library. Compound 1 suppressed kynurenine production without inhibiting indoleamine 2,3-dioxygenase 1 (IDO1) activity. The activity of 1 was derived from the inhibition of IDO1 by a metabolite of 1, O-benzylhydroxylamine (OBHA, 2a). A series of N-substituted 2a derivatives that exhibit potent activity in cell-based assays may represent effective prodrugs. Therefore, we synthesized and evaluated novel N,O-substituted hydroxylamine derivatives. The structure-activity relationships revealed that N,O-substituted hydro...
Source: Bioorganic and Medicinal Chemistry Letters - April 15, 2024 Category: Chemistry Authors: Masatomi Iijima Yasunari Otsuka Shun-Ichi Ohba Isao Momose Source Type: research
Inhibition of kynurenine production by N,O-substituted hydroxylamine derivatives
In this study, an amino acid derivative, compound 1 was discovered using a cell-based assay with our screening library. Compound 1 suppressed kynurenine production without inhibiting indoleamine 2,3-dioxygenase 1 (IDO1) activity. The activity of 1 was derived from the inhibition of IDO1 by a metabolite of 1, O-benzylhydroxylamine (OBHA, 2a). A series of N-substituted 2a derivatives that exhibit potent activity in cell-based assays may represent effective prodrugs. Therefore, we synthesized and evaluated novel N,O-substituted hydroxylamine derivatives. The structure-activity relationships revealed that N,O-substituted hydro...
Source: Bioorganic and Medicinal Chemistry Letters - April 15, 2024 Category: Chemistry Authors: Masatomi Iijima Yasunari Otsuka Shun-Ichi Ohba Isao Momose Source Type: research
Inhibition of kynurenine production by N,O-substituted hydroxylamine derivatives
In this study, an amino acid derivative, compound 1 was discovered using a cell-based assay with our screening library. Compound 1 suppressed kynurenine production without inhibiting indoleamine 2,3-dioxygenase 1 (IDO1) activity. The activity of 1 was derived from the inhibition of IDO1 by a metabolite of 1, O-benzylhydroxylamine (OBHA, 2a). A series of N-substituted 2a derivatives that exhibit potent activity in cell-based assays may represent effective prodrugs. Therefore, we synthesized and evaluated novel N,O-substituted hydroxylamine derivatives. The structure-activity relationships revealed that N,O-substituted hydro...
Source: Bioorganic and Medicinal Chemistry Letters - April 15, 2024 Category: Chemistry Authors: Masatomi Iijima Yasunari Otsuka Shun-Ichi Ohba Isao Momose Source Type: research
Modification of the phenyl ring B of phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates by pyridinyl moiety leads to novel antimitotics targeting the colchicine-binding site
Bioorg Med Chem Lett. 2024 Apr 11:129745. doi: 10.1016/j.bmcl.2024.129745. Online ahead of print.ABSTRACTA series of 8 novel pyridinyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PYRIB-SOs) were designed, prepared and evaluated for their mechanism of action. PYRIB-SOs were found to have antiproliferative activity in the nanomolar to submicromolar range on several breast cancer cell lines. Moreover, subsequent biofunctional assays indicated that the most potent PYRIB-SOs 1-3 act as antimitotics binding to the colchicine-binding site (C-BS) of α, β-tubulin and that they arrest the cell cycle progression in the G2/M phase....
Source: Bioorganic and Medicinal Chemistry Letters - April 13, 2024 Category: Chemistry Authors: Vincent Ouellette Chahrazed Bouzriba Atziri Corin Chavez Alvarez Genevi ève Hamel-Côté S ébastien Fortin Source Type: research
Fluorine-18 labeling PEGylated 6-boronotryptophan for PET scanning of mice for assessing the pharmacokinetics for boron neutron capture therapy of brain tumors
Bioorg Med Chem Lett. 2024 Apr 11;105:129744. doi: 10.1016/j.bmcl.2024.129744. Online ahead of print.ABSTRACTTwo tryptophan compound classes 5- and 6-borono PEGylated boronotryptophan derivatives have been prepared for assessing their aqueous solubility as formulation of injections for boron neutron capture therapy (BNCT). The PEGylation has improved their aqueous solubility thereby increasing their test concentration in 1 mM without suffering from toxicity. In-vitro uptake assay of PEGylated 5- and 6-boronotryptophan showed that the B-10 concentration can reach 15-50 ppm in U87 cell whereas the uptake in LN229 cell varies...
Source: Bioorganic and Medicinal Chemistry Letters - April 13, 2024 Category: Chemistry Authors: Xiang-Ping Chen Fu-Chun Hsu Kwei-Yuan Huang Teng-San Hsieh Shiou-Shiow Farn Rong-Jiun Sheu Chung-Shan Yu Source Type: research
Discovery andsynthesis of novel benzoylhydrazone neuraminidase inhibitors
Bioorg Med Chem Lett. 2024 Apr 10:129743. doi: 10.1016/j.bmcl.2024.129743. Online ahead of print.ABSTRACTNeuraminidase (NA) serves as a promising target for the exploration and development of anti-influenza drugs. In this work, lead compound 5 was discovered through pharmacophore-based virtual screening and molecular dynamics simulation, and 14 new compounds were obtained by modifying the lead compound 5 based on pharmacophore features. The biological activity test shows that 5n (IC50 = 0.13 μM) has a better inhibitory effect on wild-type NA (H5N1), while 5i (IC50 = 0.44 μM) has a prominent inhibitory effect on mutant NA...
Source: Bioorganic and Medicinal Chemistry Letters - April 12, 2024 Category: Chemistry Authors: Shi Kai Fu Li Ping Cheng Source Type: research
Discovery of novel nucleoside derivatives as selective lysine acetyltransferase p300 inhibitors for cancer therapy
In this study, we designed and optimized a series of lysine acetyltransferase p300 selective inhibitors bearing a nucleoside scaffold. Most compounds showed excellent inhibitory activity against p300 with IC50 ranging from 0.18 to 9.90 μM, except for J16, J29, J40, and J48. None of the compounds showed inhibitory activity against CBP (inhibition rate < 50 % at 10 µM). Then the cytotoxicity of the compounds against a series of cancer cells were evaluated. Compounds J31 and J32 showed excellent proliferation inhibitory activity on cancer cells T47D and H520 with desirable selectivity profile of p300 over CBP. These comp...
Source: Bioorganic and Medicinal Chemistry Letters - April 11, 2024 Category: Chemistry Authors: Qiuzi Dai Zigao Yuan Qinsheng Sun Zhuolin Ao Binsheng He Yuyang Jiang Source Type: research
Retraction notice to "Preclinical metabolism of LB42908, a novel farnesyl transferase inhibitor, and its effects on the cytochrome P450 isozyme activities" [Bioorg. Med. Chem. Lett. 22(9) (2012) 3067-3071]
Bioorg Med Chem Lett. 2024 Apr 10:129734. doi: 10.1016/j.bmcl.2024.129734. Online ahead of print.NO ABSTRACTPMID:38604924 | DOI:10.1016/j.bmcl.2024.129734 (Source: Bioorganic and Medicinal Chemistry Letters)
Source: Bioorganic and Medicinal Chemistry Letters - April 11, 2024 Category: Chemistry Authors: Minsun Chang Sung-Hak Lee Ho Jun Kim Jong-Sung Koh Aeri Kim Source Type: research
Discovery of novel nucleoside derivatives as selective lysine acetyltransferase p300 inhibitors for cancer therapy
In this study, we designed and optimized a series of lysine acetyltransferase p300 selective inhibitors bearing a nucleoside scaffold. Most compounds showed excellent inhibitory activity against p300 with IC50 ranging from 0.18 to 9.90 μM, except for J16, J29, J40, and J48. None of the compounds showed inhibitory activity against CBP (inhibition rate < 50 % at 10 µM). Then the cytotoxicity of the compounds against a series of cancer cells were evaluated. Compounds J31 and J32 showed excellent proliferation inhibitory activity on cancer cells T47D and H520 with desirable selectivity profile of p300 over CBP. These comp...
Source: Bioorganic and Medicinal Chemistry Letters - April 11, 2024 Category: Chemistry Authors: Qiuzi Dai Zigao Yuan Qinsheng Sun Zhuolin Ao Binsheng He Yuyang Jiang Source Type: research
Retraction notice to "Preclinical metabolism of LB42908, a novel farnesyl transferase inhibitor, and its effects on the cytochrome P450 isozyme activities" [Bioorg. Med. Chem. Lett. 22(9) (2012) 3067-3071]
Bioorg Med Chem Lett. 2024 Apr 10:129734. doi: 10.1016/j.bmcl.2024.129734. Online ahead of print.NO ABSTRACTPMID:38604924 | DOI:10.1016/j.bmcl.2024.129734 (Source: Bioorganic and Medicinal Chemistry Letters)
Source: Bioorganic and Medicinal Chemistry Letters - April 11, 2024 Category: Chemistry Authors: Minsun Chang Sung-Hak Lee Ho Jun Kim Jong-Sung Koh Aeri Kim Source Type: research
The mechanism of covalent inhibition of LAR phosphatase by illudalic acid
Bioorg Med Chem Lett. 2024 Apr 8:129740. doi: 10.1016/j.bmcl.2024.129740. Online ahead of print.ABSTRACTLeukocyte antigen-related (LAR) phosphatase is a receptor-type protein tyrosine phosphatase involved in cellular signaling and associated with human disease including cancer and metabolic disorders. Selective inhibition of LAR phosphatase activity by well characterized and well validated small molecules would provide key insights into the roles of LAR phosphatase in health and disease, but identifying selective inhibitors of LAR phosphatase activity has been challenging. Recently, we described potent and selective inhibi...
Source: Bioorganic and Medicinal Chemistry Letters - April 10, 2024 Category: Chemistry Authors: Daniel T Hansen Nicole J Rueb Nathan D Levinzon Thomas E Cheatham Robert Gaston Kh Tanvir Ahmed Sandra Osburn-Staker James E Cox Gregory B Dudley Amy M Barrios Source Type: research
Structural modification of tanshinone IIA and their α-glucosidase inhibitory activity
Bioorg Med Chem Lett. 2024 Apr 8:129736. doi: 10.1016/j.bmcl.2024.129736. Online ahead of print.ABSTRACTα-Glucosidase is one of the therapeutic approaches for treating type 2 diabetes mellitus. Almost 95 % of diabetes patients worldwide have been diagnosed with type 2 diabetes, resulting in 1.5 million fatalities each year. Newly synthesized oxazole-based tanshinone IIA derivatives (1a-n) were designed and evaluated for their inhibitory activity against α-glucosidase enzyme. Eight compounds (1a-d, 1f-g, 1j, and 1m) demonstrated excellent inhibition with IC50 values ranging from 0.73 ± 0.11 to 9.46 ± 0.57 μM as compare...
Source: Bioorganic and Medicinal Chemistry Letters - April 10, 2024 Category: Chemistry Authors: Mutita Kongphet Hoa Tai Xuan Hang Thanh The Ngo Thi-Kim-Dung Le Warinthorn Chavasiri Source Type: research
Insights into the structure-activity relationship of the anticancer compound ZJ-101: A role played by the amide moiety
Bioorg Med Chem Lett. 2024 Apr 8:129741. doi: 10.1016/j.bmcl.2024.129741. Online ahead of print.ABSTRACTZJ-101, a structurally simplified analog of marine natural product superstolide A, was previously designed and synthesized in our laboratory. In the present study four new analogs of ZJ-101 were designed and synthesized to investigate the structure-activity relationship of the acetamide moiety of the molecule. The biological evaluation showed that the amide moiety is important for the molecule's anticancer activity. Replacing the amide with other unctional groups such as a sulfonamide group, a carbamate group, and a urea...
Source: Bioorganic and Medicinal Chemistry Letters - April 10, 2024 Category: Chemistry Authors: Haibo Qiu Shan Qian Sarah A Head Phillip R Sanchez Jun O Liu Zhendong Jin Source Type: research
The discovery of an anti-inflammatory monoterpenoid, neoroseoside from the Zea mays
Bioorg Med Chem Lett. 2024 Apr 8:129737. doi: 10.1016/j.bmcl.2024.129737. Online ahead of print.ABSTRACTA new monoterpenoid, neoroseoside (1), along with two previously reported compounds, 2″-O-α-l-rhamnosyl-6-C-fucosylluteolin (2) and farobin A (3) were isolated from the Zea mays. The structure of compound 1 was determined through the analysis spectroscopic data, including mass spectrometry (MS), infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR) data. The absolute configurations of 1 were deduced from the comparing the values of optical rotations and from the interpretation of electronic circular dichroi...
Source: Bioorganic and Medicinal Chemistry Letters - April 10, 2024 Category: Chemistry Authors: Hui Tan Hyun-Jin Lee Prima F Hillman Eun-Young Lee Chaeyoung Lee Eun Kyoung Seo Mi Ja Lee Sang-Jip Nam Source Type: research
