Biocompatible conjugated polymer nanoparticles labeled with < sup > 225 < /sup > Ac for tumor endoradiotherapy
Bioorg Med Chem. 2023 Nov 4;96:117517. doi: 10.1016/j.bmc.2023.117517. Online ahead of print.ABSTRACTRecently, endoradiotherapy based on actinium-225 (225Ac) has attracted increasing attention, which is due to its α particles can generate maximal damage to cancer cells while minimizing unnecessary radiation effects on healthy tissues. Herein, 111In/225Ac-radiolabeled conjugated polymer nanoparticles (CPNs) coated with amphiphilic polymer DSPE-PEG-DOTA have been developed as a new injectable nano-radiopharmaceuticals for cancer endoradiotherapy under the guidance of nuclear imaging. Single photon emission computed tomograp...
Source: Bioorganic and Medicinal Chemistry - November 8, 2023 Category: Chemistry Authors: Xijian Chen Ranxi Liang Weihao Liu Huan Ma Chiyao Bai Yao Xiong Tu Lan Jiali Liao Yuanyou Yang Jijun Yang Feize Li Ning Liu Source Type: research
Harvesting phosphorus-containing moieties for their antibacterial effects
Bioorg Med Chem. 2023 Nov 2;96:117512. doi: 10.1016/j.bmc.2023.117512. Online ahead of print.ABSTRACTClinically manifested resistance of bacteria to antibiotics has emerged as a global threat to society and there is an urgent need for the development of novel classes of antibacterial agents. Recently, the use of phosphorus in antibacterial agents has been explored in quite an unprecedent manner. In this comprehensive review, we summarize the use of phosphorus-containing moieties (phosphonates, phosphonamidates, phosphonopeptides, phosphates, phosphoramidates, phosphinates, phosphine oxides, and phosphoniums) in compounds w...
Source: Bioorganic and Medicinal Chemistry - November 8, 2023 Category: Chemistry Authors: Manuela Vor áčová Matej Zore Jari Yli-Kauhaluoma Paula Kiuru Source Type: research
Synthesis and biological evaluation of indane-based fluorescent probes for detection of amyloid- β aggregates in Alzheimer's disease
Bioorg Med Chem. 2023 Nov 3;95:117513. doi: 10.1016/j.bmc.2023.117513. Online ahead of print.ABSTRACTIn this article, the development of fluorescent imaging probes for the detection of Alzheimer's disease (AD)-associated protein aggregates is described. Indane derivatives with a donor-π-acceptor (D-π-A) structure were designed and synthesized. The probes were evaluated for their ability to bind to β-amyloid (Aβ) protein aggregates, which are a key pathological hallmark of AD. The results showed that several probes exhibited significant changes in fluorescence intensity at wavelengths greater than 600 nm when they were ...
Source: Bioorganic and Medicinal Chemistry - November 6, 2023 Category: Chemistry Authors: Hyunseung Lee Yihoon Kim Hira Aziz Dong-Min Kang Jaewoon Lee Sujin Lee Sunhwa Jung Suyeon Hyeon Hyunah Choo Ghilsoo Nam Yun Kyung Kim Sungsu Lim Sun-Joon Min Source Type: research
Discovery of a potent and selective human AC2 inhibitor based on 7-deazapurine analogues of adefovir
Bioorg Med Chem. 2023 Oct 26;95:117508. doi: 10.1016/j.bmc.2023.117508. Online ahead of print.ABSTRACTAdefovir based acyclic nucleoside phosphonates were previously shown to modulate bacterial and, to a certain extent, human adenylate cyclases (mACs). In this work, a series of 24 novel 7-substituted 7-deazaadefovir analogues were synthesized in the form of prodrugs. Twelve analogues were single-digit micromolar inhibitors of Bordetella pertussis adenylate cyclase toxin with no cytotoxicity to J774A.1 macrophages. In HEK293 cell-based assays, compound 14 was identified as a potent (IC50 = 4.45 μM), non-toxic, and selective...
Source: Bioorganic and Medicinal Chemistry - November 6, 2023 Category: Chemistry Authors: Pavel Kraina Michal Česnek Eva Tlou šťová Helena Mertl íková-Kaiserová Camryn J Fulton Emily K Davidson Brenton P Smith Val J Watts Zlatko Janeba Source Type: research
Synthesis and biological evaluation of indane-based fluorescent probes for detection of amyloid- β aggregates in Alzheimer's disease
Bioorg Med Chem. 2023 Nov 3;95:117513. doi: 10.1016/j.bmc.2023.117513. Online ahead of print.ABSTRACTIn this article, the development of fluorescent imaging probes for the detection of Alzheimer's disease (AD)-associated protein aggregates is described. Indane derivatives with a donor-π-acceptor (D-π-A) structure were designed and synthesized. The probes were evaluated for their ability to bind to β-amyloid (Aβ) protein aggregates, which are a key pathological hallmark of AD. The results showed that several probes exhibited significant changes in fluorescence intensity at wavelengths greater than 600 nm when they were ...
Source: Bioorganic and Medicinal Chemistry - November 6, 2023 Category: Chemistry Authors: Hyunseung Lee Yihoon Kim Hira Aziz Dong-Min Kang Jaewoon Lee Sujin Lee Sunhwa Jung Suyeon Hyeon Hyunah Choo Ghilsoo Nam Yun Kyung Kim Sungsu Lim Sun-Joon Min Source Type: research
Discovery of a potent and selective human AC2 inhibitor based on 7-deazapurine analogues of adefovir
Bioorg Med Chem. 2023 Oct 26;95:117508. doi: 10.1016/j.bmc.2023.117508. Online ahead of print.ABSTRACTAdefovir based acyclic nucleoside phosphonates were previously shown to modulate bacterial and, to a certain extent, human adenylate cyclases (mACs). In this work, a series of 24 novel 7-substituted 7-deazaadefovir analogues were synthesized in the form of prodrugs. Twelve analogues were single-digit micromolar inhibitors of Bordetella pertussis adenylate cyclase toxin with no cytotoxicity to J774A.1 macrophages. In HEK293 cell-based assays, compound 14 was identified as a potent (IC50 = 4.45 μM), non-toxic, and selective...
Source: Bioorganic and Medicinal Chemistry - November 6, 2023 Category: Chemistry Authors: Pavel Kraina Michal Česnek Eva Tlou šťová Helena Mertl íková-Kaiserová Camryn J Fulton Emily K Davidson Brenton P Smith Val J Watts Zlatko Janeba Source Type: research
Synthesis, anti-inflammatory activity, inverse molecular docking, and acid dissociation constants of new naphthoquinone-thiazole hybrids
Bioorg Med Chem. 2023 Oct 31;95:117510. doi: 10.1016/j.bmc.2023.117510. Online ahead of print.ABSTRACTChronic Inflammation is associated with various types of diseases that involves pro-inflammatory cytokines like IL-6 and TNF-α. High costs and serious side effects of available anti-inflammatory/immunomodulatory drugs led us to design new compounds with promising anti-inflammatory activities. Many drugs and biologically important compounds involve naphthoquinone and thiazole moieties in their core structures. Thereby, here we report the synthesis, characterization and anti-inflammatory activities of new naphthoquinone thi...
Source: Bioorganic and Medicinal Chemistry - November 5, 2023 Category: Chemistry Authors: Cagla Efeoglu Sena Taskin Ozge Selcuk Begum Celik Ece Tumkaya Abdulilah Ece Hayati Sari Zeynel Seferoglu Furkan Ayaz Yahya Nural Source Type: research
Synthesis, anti-inflammatory activity, inverse molecular docking, and acid dissociation constants of new naphthoquinone-thiazole hybrids
Bioorg Med Chem. 2023 Oct 31;95:117510. doi: 10.1016/j.bmc.2023.117510. Online ahead of print.ABSTRACTChronic Inflammation is associated with various types of diseases that involves pro-inflammatory cytokines like IL-6 and TNF-α. High costs and serious side effects of available anti-inflammatory/immunomodulatory drugs led us to design new compounds with promising anti-inflammatory activities. Many drugs and biologically important compounds involve naphthoquinone and thiazole moieties in their core structures. Thereby, here we report the synthesis, characterization and anti-inflammatory activities of new naphthoquinone thi...
Source: Bioorganic and Medicinal Chemistry - November 5, 2023 Category: Chemistry Authors: Cagla Efeoglu Sena Taskin Ozge Selcuk Begum Celik Ece Tumkaya Abdulilah Ece Hayati Sari Zeynel Seferoglu Furkan Ayaz Yahya Nural Source Type: research
Development of decoy oligonucleotide-warheaded chimeric molecules targeting STAT3
In this study, we applied an oligonucleotide-warheaded PROTAC technology to induce the degradation of signal transducer and activator of transcription 3 (STAT3), which is a hard-to-target protein. A double-stranded decoy oligonucleotide specific to STAT3 was conjugated to E3 binders (pomalidomide, VH032, and LCL161) to generate PROTAC molecules that recruited different E3 ubiquitin ligases cereblon (CRBN), von Hippel-Lindau (VHL), and inhibitor of apoptosis protein (IAP), respectively. One of the resulting PROTAC molecules, POM-STAT3, which recruits CRBN, potently induces STAT3 degradation. STAT3 degradation by POM-STAT3 w...
Source: Bioorganic and Medicinal Chemistry - November 3, 2023 Category: Chemistry Authors: Po-Chang Shih Miyako Naganuma Genichiro Tsuji Yosuke Demizu Mikihiko Naito Source Type: research
A novel genetically-encoded bicyclic peptide inhibitor of human urokinase-type plasminogen activator with better cross-reactivity toward the murine orthologue
Bioorg Med Chem. 2023 Oct 12;95:117499. doi: 10.1016/j.bmc.2023.117499. Online ahead of print.ABSTRACTThe inhibition of human urokinase-type plasminogen activator (huPA), a serine protease that plays an important role in pericellular proteolysis, is a promising strategy to decrease the invasive and metastatic activity of tumour cells. However, the generation of selective small molecule huPA inhibitors has proven to be challenging due to the high structural similarity of huPA to other paralogue serine proteases. Efforts to generate more specific therapies have led to the development of cyclic peptide-based inhibitors with m...
Source: Bioorganic and Medicinal Chemistry - October 25, 2023 Category: Chemistry Authors: Ylenia Mazzocato Stefano Perin Julia Morales-Sanfrutos Zhanna Romanyuk Stefano Pluda Laura Acquasaliente Giuseppe Borsato Vincenzo De Filippis Alessandro Scarso Alessandro Angelini Source Type: research
A novel genetically-encoded bicyclic peptide inhibitor of human urokinase-type plasminogen activator with better cross-reactivity toward the murine orthologue
Bioorg Med Chem. 2023 Oct 12;95:117499. doi: 10.1016/j.bmc.2023.117499. Online ahead of print.ABSTRACTThe inhibition of human urokinase-type plasminogen activator (huPA), a serine protease that plays an important role in pericellular proteolysis, is a promising strategy to decrease the invasive and metastatic activity of tumour cells. However, the generation of selective small molecule huPA inhibitors has proven to be challenging due to the high structural similarity of huPA to other paralogue serine proteases. Efforts to generate more specific therapies have led to the development of cyclic peptide-based inhibitors with m...
Source: Bioorganic and Medicinal Chemistry - October 25, 2023 Category: Chemistry Authors: Ylenia Mazzocato Stefano Perin Julia Morales-Sanfrutos Zhanna Romanyuk Stefano Pluda Laura Acquasaliente Giuseppe Borsato Vincenzo De Filippis Alessandro Scarso Alessandro Angelini Source Type: research
A novel genetically-encoded bicyclic peptide inhibitor of human urokinase-type plasminogen activator with better cross-reactivity toward the murine orthologue
Bioorg Med Chem. 2023 Oct 12;95:117499. doi: 10.1016/j.bmc.2023.117499. Online ahead of print.ABSTRACTThe inhibition of human urokinase-type plasminogen activator (huPA), a serine protease that plays an important role in pericellular proteolysis, is a promising strategy to decrease the invasive and metastatic activity of tumour cells. However, the generation of selective small molecule huPA inhibitors has proven to be challenging due to the high structural similarity of huPA to other paralogue serine proteases. Efforts to generate more specific therapies have led to the development of cyclic peptide-based inhibitors with m...
Source: Bioorganic and Medicinal Chemistry - October 25, 2023 Category: Chemistry Authors: Ylenia Mazzocato Stefano Perin Julia Morales-Sanfrutos Zhanna Romanyuk Stefano Pluda Laura Acquasaliente Giuseppe Borsato Vincenzo De Filippis Alessandro Scarso Alessandro Angelini Source Type: research
A novel genetically-encoded bicyclic peptide inhibitor of human urokinase-type plasminogen activator with better cross-reactivity toward the murine orthologue
Bioorg Med Chem. 2023 Oct 12;95:117499. doi: 10.1016/j.bmc.2023.117499. Online ahead of print.ABSTRACTThe inhibition of human urokinase-type plasminogen activator (huPA), a serine protease that plays an important role in pericellular proteolysis, is a promising strategy to decrease the invasive and metastatic activity of tumour cells. However, the generation of selective small molecule huPA inhibitors has proven to be challenging due to the high structural similarity of huPA to other paralogue serine proteases. Efforts to generate more specific therapies have led to the development of cyclic peptide-based inhibitors with m...
Source: Bioorganic and Medicinal Chemistry - October 25, 2023 Category: Chemistry Authors: Ylenia Mazzocato Stefano Perin Julia Morales-Sanfrutos Zhanna Romanyuk Stefano Pluda Laura Acquasaliente Giuseppe Borsato Vincenzo De Filippis Alessandro Scarso Alessandro Angelini Source Type: research
A novel genetically-encoded bicyclic peptide inhibitor of human urokinase-type plasminogen activator with better cross-reactivity toward the murine orthologue
Bioorg Med Chem. 2023 Oct 12;95:117499. doi: 10.1016/j.bmc.2023.117499. Online ahead of print.ABSTRACTThe inhibition of human urokinase-type plasminogen activator (huPA), a serine protease that plays an important role in pericellular proteolysis, is a promising strategy to decrease the invasive and metastatic activity of tumour cells. However, the generation of selective small molecule huPA inhibitors has proven to be challenging due to the high structural similarity of huPA to other paralogue serine proteases. Efforts to generate more specific therapies have led to the development of cyclic peptide-based inhibitors with m...
Source: Bioorganic and Medicinal Chemistry - October 25, 2023 Category: Chemistry Authors: Ylenia Mazzocato Stefano Perin Julia Morales-Sanfrutos Zhanna Romanyuk Stefano Pluda Laura Acquasaliente Giuseppe Borsato Vincenzo De Filippis Alessandro Scarso Alessandro Angelini Source Type: research
A novel genetically-encoded bicyclic peptide inhibitor of human urokinase-type plasminogen activator with better cross-reactivity toward the murine orthologue
Bioorg Med Chem. 2023 Oct 12;95:117499. doi: 10.1016/j.bmc.2023.117499. Online ahead of print.ABSTRACTThe inhibition of human urokinase-type plasminogen activator (huPA), a serine protease that plays an important role in pericellular proteolysis, is a promising strategy to decrease the invasive and metastatic activity of tumour cells. However, the generation of selective small molecule huPA inhibitors has proven to be challenging due to the high structural similarity of huPA to other paralogue serine proteases. Efforts to generate more specific therapies have led to the development of cyclic peptide-based inhibitors with m...
Source: Bioorganic and Medicinal Chemistry - October 25, 2023 Category: Chemistry Authors: Ylenia Mazzocato Stefano Perin Julia Morales-Sanfrutos Zhanna Romanyuk Stefano Pluda Laura Acquasaliente Giuseppe Borsato Vincenzo De Filippis Alessandro Scarso Alessandro Angelini Source Type: research
