Design, synthesis and biological evaluation of aryloxy thiophosphoramidate triesters of anticancer nucleoside analogues
Bioorg Med Chem. 2024 Mar 25;103:117696. doi: 10.1016/j.bmc.2024.117696. Online ahead of print.ABSTRACTAryloxy phosphoroamidate triesters, known as ProTides, are a class of prodrugs developed to enhance the physicochemical and pharmacological properties of therapeutic nucleosides. This approach has been extensively investigated in the antiviral and anticancer areas leading to three prodrugs on the market and several others in clinical stage. In this article we have prepared the PS analogues of three ProTides that have reached the clinic as anticancer agents. These novel PS ProTides were tested for their capacity in enzymat...
Source: Bioorganic and Medicinal Chemistry - March 28, 2024 Category: Chemistry Authors: Michaela Serpi Samule di Ciano Fabrizio Pertusati Source Type: research
Design, synthesis and biological evaluation of aryloxy thiophosphoramidate triesters of anticancer nucleoside analogues
Bioorg Med Chem. 2024 Mar 25;103:117696. doi: 10.1016/j.bmc.2024.117696. Online ahead of print.ABSTRACTAryloxy phosphoroamidate triesters, known as ProTides, are a class of prodrugs developed to enhance the physicochemical and pharmacological properties of therapeutic nucleosides. This approach has been extensively investigated in the antiviral and anticancer areas leading to three prodrugs on the market and several others in clinical stage. In this article we have prepared the PS analogues of three ProTides that have reached the clinic as anticancer agents. These novel PS ProTides were tested for their capacity in enzymat...
Source: Bioorganic and Medicinal Chemistry - March 28, 2024 Category: Chemistry Authors: Michaela Serpi Samule di Ciano Fabrizio Pertusati Source Type: research
An insight into the mechanistic role of (-)-Ampelopsin F from Vatica chinensis L. in inducing insulin secretion in pancreatic beta cells
In this study, we elucidate the mechanistic insights into the insulin secretion potential of a resveratrol dimer, (-)-Ampelopsin F (AmF), isolated from the acetone extract of Vatica chinensis L. stem bark in Pancreatic Beta-TC-6 cell lines. The AmF (50 µM) treated cells exhibited a 3.5-fold increase in insulin secretion potential as compared to unstimulated cells, which was achieved through the enhancement of mitochondrial membrane hyperpolarization, elevation of intracellular calcium concentration, and upregulation of GLUT2 and glucokinase expression in pancreatic Beta-TC-6 cell lines. Furthermore, AmF effectively inhibi...
Source: Bioorganic and Medicinal Chemistry - March 24, 2024 Category: Chemistry Authors: B Prabha S Lekshmy Krishnan Billu Abraham P Jayamurthy K V Radhakrishnan Source Type: research
An insight into the mechanistic role of (-)-Ampelopsin F from Vatica chinensis L. in inducing insulin secretion in pancreatic beta cells
In this study, we elucidate the mechanistic insights into the insulin secretion potential of a resveratrol dimer, (-)-Ampelopsin F (AmF), isolated from the acetone extract of Vatica chinensis L. stem bark in Pancreatic Beta-TC-6 cell lines. The AmF (50 µM) treated cells exhibited a 3.5-fold increase in insulin secretion potential as compared to unstimulated cells, which was achieved through the enhancement of mitochondrial membrane hyperpolarization, elevation of intracellular calcium concentration, and upregulation of GLUT2 and glucokinase expression in pancreatic Beta-TC-6 cell lines. Furthermore, AmF effectively inhibi...
Source: Bioorganic and Medicinal Chemistry - March 24, 2024 Category: Chemistry Authors: B Prabha S Lekshmy Krishnan Billu Abraham P Jayamurthy K V Radhakrishnan Source Type: research
An insight into the mechanistic role of (-)-Ampelopsin F from Vatica chinensis L. in inducing insulin secretion in pancreatic beta cells
In this study, we elucidate the mechanistic insights into the insulin secretion potential of a resveratrol dimer, (-)-Ampelopsin F (AmF), isolated from the acetone extract of Vatica chinensis L. stem bark in Pancreatic Beta-TC-6 cell lines. The AmF (50 µM) treated cells exhibited a 3.5-fold increase in insulin secretion potential as compared to unstimulated cells, which was achieved through the enhancement of mitochondrial membrane hyperpolarization, elevation of intracellular calcium concentration, and upregulation of GLUT2 and glucokinase expression in pancreatic Beta-TC-6 cell lines. Furthermore, AmF effectively inhibi...
Source: Bioorganic and Medicinal Chemistry - March 24, 2024 Category: Chemistry Authors: B Prabha S Lekshmy Krishnan Billu Abraham P Jayamurthy K V Radhakrishnan Source Type: research
An insight into the mechanistic role of (-)-Ampelopsin F from Vatica chinensis L. in inducing insulin secretion in pancreatic beta cells
In this study, we elucidate the mechanistic insights into the insulin secretion potential of a resveratrol dimer, (-)-Ampelopsin F (AmF), isolated from the acetone extract of Vatica chinensis L. stem bark in Pancreatic Beta-TC-6 cell lines. The AmF (50 µM) treated cells exhibited a 3.5-fold increase in insulin secretion potential as compared to unstimulated cells, which was achieved through the enhancement of mitochondrial membrane hyperpolarization, elevation of intracellular calcium concentration, and upregulation of GLUT2 and glucokinase expression in pancreatic Beta-TC-6 cell lines. Furthermore, AmF effectively inhibi...
Source: Bioorganic and Medicinal Chemistry - March 24, 2024 Category: Chemistry Authors: B Prabha S Lekshmy Krishnan Billu Abraham P Jayamurthy K V Radhakrishnan Source Type: research
Fluorescent probes and degraders of the sterol transport protein Aster-A
Bioorg Med Chem. 2024 Mar 2;103:117673. doi: 10.1016/j.bmc.2024.117673. Online ahead of print.ABSTRACTOur understanding of sterol transport proteins (STPs) has increased exponentially in the last decades with advances in the cellular and structural biology of these important proteins. However, small molecule probes have only recently been developed for a few selected STPs. Here we describe the synthesis and evaluation of potential proteolysis-targeting chimeras (PROTACs) based on inhibitors of the STP Aster-A. Based on the reported Aster-A inhibitor autogramin-2, ten PROTACs were synthesized. Pomalidomide-based PROTACs fun...
Source: Bioorganic and Medicinal Chemistry - March 22, 2024 Category: Chemistry Authors: Nianzhe He Laura Depta Sonja Sievers Luca Laraia Source Type: research
Exploiting high-energy hydration sites for the discovery of potent peptide aldehyde inhibitors of the SARS-CoV-2 main protease with cellular antiviral activity
Bioorg Med Chem. 2024 Jan 5;103:117577. doi: 10.1016/j.bmc.2023.117577. Online ahead of print.ABSTRACTSmall-molecule antivirals that prevent the replication of the SARS-CoV-2 virus by blocking the enzymatic activity of its main protease (Mpro) are and will be a tenet of pandemic preparedness. However, the peptidic nature of such compounds often precludes the design of compounds within favorable physical property ranges, limiting cellular activity. Here we describe the discovery of peptide aldehyde Mpro inhibitors with potent enzymatic and cellular antiviral activity. This structure-activity relationship (SAR) exploration w...
Source: Bioorganic and Medicinal Chemistry - March 22, 2024 Category: Chemistry Authors: Daniel W Carney Abba E Leffler Jeffrey A Bell Asela S Chandrasinghe Cecilia Cheng Edcon Chang Adam Dornford Douglas R Dougan Leah L Frye Mary E Grimes Tim Knehans Jennifer L Knight Mallareddy Komandla Weston Lane Hubert Li Sophia R Newman Katalin Phimiste Source Type: research
Fluorescent probes and degraders of the sterol transport protein Aster-A
Bioorg Med Chem. 2024 Mar 2;103:117673. doi: 10.1016/j.bmc.2024.117673. Online ahead of print.ABSTRACTOur understanding of sterol transport proteins (STPs) has increased exponentially in the last decades with advances in the cellular and structural biology of these important proteins. However, small molecule probes have only recently been developed for a few selected STPs. Here we describe the synthesis and evaluation of potential proteolysis-targeting chimeras (PROTACs) based on inhibitors of the STP Aster-A. Based on the reported Aster-A inhibitor autogramin-2, ten PROTACs were synthesized. Pomalidomide-based PROTACs fun...
Source: Bioorganic and Medicinal Chemistry - March 22, 2024 Category: Chemistry Authors: Nianzhe He Laura Depta Sonja Sievers Luca Laraia Source Type: research
Exploiting high-energy hydration sites for the discovery of potent peptide aldehyde inhibitors of the SARS-CoV-2 main protease with cellular antiviral activity
Bioorg Med Chem. 2024 Jan 5;103:117577. doi: 10.1016/j.bmc.2023.117577. Online ahead of print.ABSTRACTSmall-molecule antivirals that prevent the replication of the SARS-CoV-2 virus by blocking the enzymatic activity of its main protease (Mpro) are and will be a tenet of pandemic preparedness. However, the peptidic nature of such compounds often precludes the design of compounds within favorable physical property ranges, limiting cellular activity. Here we describe the discovery of peptide aldehyde Mpro inhibitors with potent enzymatic and cellular antiviral activity. This structure-activity relationship (SAR) exploration w...
Source: Bioorganic and Medicinal Chemistry - March 22, 2024 Category: Chemistry Authors: Daniel W Carney Abba E Leffler Jeffrey A Bell Asela S Chandrasinghe Cecilia Cheng Edcon Chang Adam Dornford Douglas R Dougan Leah L Frye Mary E Grimes Tim Knehans Jennifer L Knight Mallareddy Komandla Weston Lane Hubert Li Sophia R Newman Katalin Phimiste Source Type: research
Corrigendum to "Genetically encoded dihydroxyphenylalanine coupled with tyrosinase for strain promoted labelling" [Bioorg. Med. Chem. 50 (2021) 116460]
Bioorg Med Chem. 2024 Mar 19:117664. doi: 10.1016/j.bmc.2024.117664. Online ahead of print.NO ABSTRACTPMID:38508900 | DOI:10.1016/j.bmc.2024.117664 (Source: Bioorganic and Medicinal Chemistry)
Source: Bioorganic and Medicinal Chemistry - March 20, 2024 Category: Chemistry Authors: Augustine George Mohan Indhu Sundarapandian Ashokraj Ganesh Shanmugam Ponesakki Ganesan Numbi Ramudu Kamini Niraikulam Ayyadurai Source Type: research
Corrigendum to "Genetically encoded dihydroxyphenylalanine coupled with tyrosinase for strain promoted labelling" [Bioorg. Med. Chem. 50 (2021) 116460]
Bioorg Med Chem. 2024 Mar 19:117664. doi: 10.1016/j.bmc.2024.117664. Online ahead of print.NO ABSTRACTPMID:38508900 | DOI:10.1016/j.bmc.2024.117664 (Source: Bioorganic and Medicinal Chemistry)
Source: Bioorganic and Medicinal Chemistry - March 20, 2024 Category: Chemistry Authors: Augustine George Mohan Indhu Sundarapandian Ashokraj Ganesh Shanmugam Ponesakki Ganesan Numbi Ramudu Kamini Niraikulam Ayyadurai Source Type: research
Corrigendum to "Genetically encoded dihydroxyphenylalanine coupled with tyrosinase for strain promoted labelling" [Bioorg. Med. Chem. 50 (2021) 116460]
Bioorg Med Chem. 2024 Mar 19:117664. doi: 10.1016/j.bmc.2024.117664. Online ahead of print.NO ABSTRACTPMID:38508900 | DOI:10.1016/j.bmc.2024.117664 (Source: Bioorganic and Medicinal Chemistry)
Source: Bioorganic and Medicinal Chemistry - March 20, 2024 Category: Chemistry Authors: Augustine George Mohan Indhu Sundarapandian Ashokraj Ganesh Shanmugam Ponesakki Ganesan Numbi Ramudu Kamini Niraikulam Ayyadurai Source Type: research
Cryptic piperazine derivatives activated by knocking out the global regulator LaeA in Aspergillus flavipes
Bioorg Med Chem. 2024 Mar 15;103:117685. doi: 10.1016/j.bmc.2024.117685. Online ahead of print.ABSTRACTGenome sequencing on an intertidal zone-derived Aspergillus flavipes strain revealed its great potential to produce secondary metabolites. To activate the cryptic compounds of A. flavipes, the global regulator flLaeA was knocked out, leading to substantial up-regulation of the expression of two NRPS-like biosynthetic gene clusters in the ΔflLaeA mutant. With a scaled-up fermentation of the ΔflLaeA strain, five compounds, including two previously undescribed piperazine derivatives flavipamides A and B (1 and 2), along wi...
Source: Bioorganic and Medicinal Chemistry - March 19, 2024 Category: Chemistry Authors: Yaping Liu Pengkun Li Changxing Qi Ziou Zha Jie Meng Chang Liu Jiapei Han Qun Zhou Zengwei Luo Jianping Wang Hucheng Zhu Ying Ye Chunmei Chen Yuan Zhou Yonghui Zhang Source Type: research
Caged xanthone derivatives to promote mitochondria-mediated apoptosis in breast cancer cells
This study aims to address this gap by introducing an innovative synthetic method for constructing a novel caged structure that incorporates a widely employed maleimide group. Drawing upon the well-established synthetic approach for dihydroxanthones previously developed within our research group, we successfully synthesized 13 new caged xanthones using the Diels-Alder reaction. Subsequently, we evaluated their anti-proliferative activity against HepG2, A549, and MDA-MB-231 cell lines. The results revealed that compound 10i exhibited IC50 values of 15.86 µM ± 1.29, 19.27 µM ± 1.58, and 12.96 µM ± 0.09 against these ce...
Source: Bioorganic and Medicinal Chemistry - March 17, 2024 Category: Chemistry Authors: Youyi Wang Huimin Zheng Xue Jiang Huaimo Wu Yi Ren Zhichao Xi Changwu Zheng Hongxi Xu Source Type: research
