Terpene-functionalized Fluoroquinolones as Potential Antimicrobials: Synthesis and Properties
This study was the first to synthesize terpene-containing conjugates of fluoroquinolones, ciprofloxacin and norfloxacin, and to evaluate their antibacterial activity against gram-positive methicillin sensitive (MSSA) and methicillin resistant (MRSA) S. aureus, gram-negative P. aeruginosa as well as antifungal activity against C. albicans. The ability of obtained fluoroquinolones to inhibit S. aureus growth was found to depend upon the presence of a linker separating the bulky terpene and fluoroquinolone fragments, and this activity diminished with increasing its length. The highest activity against MSSA was demonstrated by...
Source: ChemMedChem - October 24, 2023 Category: Chemistry Authors: Evgeniy Sergeevich Izmest'ev Pestova V Svetlana Alena I Kolesnikova Diana R Baidamshina Airat R Kayumov Svetlana A Rubtsova Source Type: research
Synergistic and additive effects of menadione in combination with antibiotics on multidrug-resistant Staphylococcus aureus: Insights from structure-function analysis of NQs
ChemMedChem. 2023 Oct 24:e202300328. doi: 10.1002/cmdc.202300328. Online ahead of print.ABSTRACTAntimicrobial resistance (AMR) has interfered with effective treatment of microbial infection and increased the risk of microbial spread, illness, and deaths. The synergistic activities of combinations of antimicrobials offer satisfactory approaches to some extent. Structurally diverse naphthoquinones (NQs) including menadione (-CH3 at C-2) exhibit substantial antimicrobial activities against multidrug-resistant (MDR) pathogens. We explored the combinations of menadione with antibiotic ciprofloxacin or ampicillin against Staphyl...
Source: ChemMedChem - October 24, 2023 Category: Chemistry Authors: Nishigandha S Mone Sahil Syed Palanisamy Ravichandiran Ekta E Kamble Karishma R Pardesi Sunita Salunke-Gawali Mansi Rai Ajay Vikram Singh Sarada Prasad Dakua Byung-Hyun Park Dong Jin Yoo Surekha K Satpute Source Type: research
Terpene-functionalized Fluoroquinolones as Potential Antimicrobials: Synthesis and Properties
This study was the first to synthesize terpene-containing conjugates of fluoroquinolones, ciprofloxacin and norfloxacin, and to evaluate their antibacterial activity against gram-positive methicillin sensitive (MSSA) and methicillin resistant (MRSA) S. aureus, gram-negative P. aeruginosa as well as antifungal activity against C. albicans. The ability of obtained fluoroquinolones to inhibit S. aureus growth was found to depend upon the presence of a linker separating the bulky terpene and fluoroquinolone fragments, and this activity diminished with increasing its length. The highest activity against MSSA was demonstrated by...
Source: ChemMedChem - October 24, 2023 Category: Chemistry Authors: Evgeniy Sergeevich Izmest'ev Pestova V Svetlana Alena I Kolesnikova Diana R Baidamshina Airat R Kayumov Svetlana A Rubtsova Source Type: research
Synergistic and additive effects of menadione in combination with antibiotics on multidrug-resistant Staphylococcus aureus: Insights from structure-function analysis of NQs
ChemMedChem. 2023 Oct 24:e202300328. doi: 10.1002/cmdc.202300328. Online ahead of print.ABSTRACTAntimicrobial resistance (AMR) has interfered with effective treatment of microbial infection and increased the risk of microbial spread, illness, and deaths. The synergistic activities of combinations of antimicrobials offer satisfactory approaches to some extent. Structurally diverse naphthoquinones (NQs) including menadione (-CH3 at C-2) exhibit substantial antimicrobial activities against multidrug-resistant (MDR) pathogens. We explored the combinations of menadione with antibiotic ciprofloxacin or ampicillin against Staphyl...
Source: ChemMedChem - October 24, 2023 Category: Chemistry Authors: Nishigandha S Mone Sahil Syed Palanisamy Ravichandiran Ekta E Kamble Karishma R Pardesi Sunita Salunke-Gawali Mansi Rai Ajay Vikram Singh Sarada Prasad Dakua Byung-Hyun Park Dong Jin Yoo Surekha K Satpute Source Type: research
Terpene-functionalized Fluoroquinolones as Potential Antimicrobials: Synthesis and Properties
This study was the first to synthesize terpene-containing conjugates of fluoroquinolones, ciprofloxacin and norfloxacin, and to evaluate their antibacterial activity against gram-positive methicillin sensitive (MSSA) and methicillin resistant (MRSA) S. aureus, gram-negative P. aeruginosa as well as antifungal activity against C. albicans. The ability of obtained fluoroquinolones to inhibit S. aureus growth was found to depend upon the presence of a linker separating the bulky terpene and fluoroquinolone fragments, and this activity diminished with increasing its length. The highest activity against MSSA was demonstrated by...
Source: ChemMedChem - October 24, 2023 Category: Chemistry Authors: Evgeniy Sergeevich Izmest'ev Pestova V Svetlana Alena I Kolesnikova Diana R Baidamshina Airat R Kayumov Svetlana A Rubtsova Source Type: research
Synergistic and additive effects of menadione in combination with antibiotics on multidrug-resistant Staphylococcus aureus: Insights from structure-function analysis of NQs
ChemMedChem. 2023 Oct 24:e202300328. doi: 10.1002/cmdc.202300328. Online ahead of print.ABSTRACTAntimicrobial resistance (AMR) has interfered with effective treatment of microbial infection and increased the risk of microbial spread, illness, and deaths. The synergistic activities of combinations of antimicrobials offer satisfactory approaches to some extent. Structurally diverse naphthoquinones (NQs) including menadione (-CH3 at C-2) exhibit substantial antimicrobial activities against multidrug-resistant (MDR) pathogens. We explored the combinations of menadione with antibiotic ciprofloxacin or ampicillin against Staphyl...
Source: ChemMedChem - October 24, 2023 Category: Chemistry Authors: Nishigandha S Mone Sahil Syed Palanisamy Ravichandiran Ekta E Kamble Karishma R Pardesi Sunita Salunke-Gawali Mansi Rai Ajay Vikram Singh Sarada Prasad Dakua Byung-Hyun Park Dong Jin Yoo Surekha K Satpute Source Type: research
Terpene-functionalized Fluoroquinolones as Potential Antimicrobials: Synthesis and Properties
This study was the first to synthesize terpene-containing conjugates of fluoroquinolones, ciprofloxacin and norfloxacin, and to evaluate their antibacterial activity against gram-positive methicillin sensitive (MSSA) and methicillin resistant (MRSA) S. aureus, gram-negative P. aeruginosa as well as antifungal activity against C. albicans. The ability of obtained fluoroquinolones to inhibit S. aureus growth was found to depend upon the presence of a linker separating the bulky terpene and fluoroquinolone fragments, and this activity diminished with increasing its length. The highest activity against MSSA was demonstrated by...
Source: ChemMedChem - October 24, 2023 Category: Chemistry Authors: Evgeniy Sergeevich Izmest'ev Pestova V Svetlana Alena I Kolesnikova Diana R Baidamshina Airat R Kayumov Svetlana A Rubtsova Source Type: research
Synergistic and additive effects of menadione in combination with antibiotics on multidrug-resistant Staphylococcus aureus: Insights from structure-function analysis of NQs
ChemMedChem. 2023 Oct 24:e202300328. doi: 10.1002/cmdc.202300328. Online ahead of print.ABSTRACTAntimicrobial resistance (AMR) has interfered with effective treatment of microbial infection and increased the risk of microbial spread, illness, and deaths. The synergistic activities of combinations of antimicrobials offer satisfactory approaches to some extent. Structurally diverse naphthoquinones (NQs) including menadione (-CH3 at C-2) exhibit substantial antimicrobial activities against multidrug-resistant (MDR) pathogens. We explored the combinations of menadione with antibiotic ciprofloxacin or ampicillin against Staphyl...
Source: ChemMedChem - October 24, 2023 Category: Chemistry Authors: Nishigandha S Mone Sahil Syed Palanisamy Ravichandiran Ekta E Kamble Karishma R Pardesi Sunita Salunke-Gawali Mansi Rai Ajay Vikram Singh Sarada Prasad Dakua Byung-Hyun Park Dong Jin Yoo Surekha K Satpute Source Type: research
Synergistic Effects of Tranylcypromine and NRF2 inhibitor: A Repurposing Strategy for Effective Cancer Therapy
In this study, we investigated combining Tranylcypromine (TCP) with a number of well-characterized drugs. Among these combinations, ML385 exhibited synergistic effects in combination with TCP. Specifically, our results showed that the combination of TCP and ML385 resulted in a significant reduction in tumor proliferation while neither drug affected cancer cell growth meaningfully on its own. While further studies are needed to understand fully the extent of the synergistic efficacy, the underlying respective mechanisms and the potential side effects of this approach, our study has yielded a promising start for the developm...
Source: ChemMedChem - October 23, 2023 Category: Chemistry Authors: Delos Chen Skye Chen Fangheng Zhou Lan Bo Chen Ming-Wei Chen Source Type: research
(R)-PFI-2 Analogues as Substrates and Inhibitors of Histone Lysine Methyltransferase SETD7
ChemMedChem. 2023 Oct 23:e202300457. doi: 10.1002/cmdc.202300457. Online ahead of print.ABSTRACT(R)-PFI-2 is a histone substrate-competitive inhibitor of the human histone lysine monomethyltransferase SETD7. Aimed at developing potent inhibitors of SETD7 that can also act as small molecule substrates, we replaced the pyrrolidine ring of (R)-PFI-2 with several side chains bearing nucleophilic functional groups. We explored the inhibitory activity of 20 novel (R)-PFI-2 analogues, and found that the most potent analogue has a hydroxyethyl side chain (7). SETD7's ability to catalyse methylation of (R)-PFI-2-based small molecul...
Source: ChemMedChem - October 23, 2023 Category: Chemistry Authors: Miriam Porzberg Danny Lenstra Eddy Damen Richard Blaauw Floris Rutjes Anita Wegert Jasmin Mecinovic Source Type: research
Optimization of ketobenzothiazole-based type II transmembrane serine protease inhibitors to block H1N1 influenza virus replication
ChemMedChem. 2023 Oct 21:e202300458. doi: 10.1002/cmdc.202300458. Online ahead of print.ABSTRACTHuman influenza viruses cause acute respiratory symptoms that can lead to death. Due to the emergence of antiviral drug-resistant strains, there is an urgent requirement for novel antiviral agents and innovative therapeutic strategies. Using the peptidomimetic ketobenzothiazole protease inhibitor RQAR-Kbt (IN-1, aka N-0100) as a starting point, we report how substituting P2 and P4 positions with natural and unnatural amino acids can modulate the inhibition potency toward matriptase, a prototypical type II transmembrane serine pr...
Source: ChemMedChem - October 21, 2023 Category: Chemistry Authors: Éloïc Colombo Antoine D ésilets Malihe Hassanzadeh Gabriel Lemieux Isabelle Marois Dominic Cliche Julien A Delbrouck Alexandre Murza Fran çois Jean Eric Marsault Martin V Richter Richard Leduc Pierre-Luc Boudreault Source Type: research
Optimization of ketobenzothiazole-based type II transmembrane serine protease inhibitors to block H1N1 influenza virus replication
ChemMedChem. 2023 Oct 21:e202300458. doi: 10.1002/cmdc.202300458. Online ahead of print.ABSTRACTHuman influenza viruses cause acute respiratory symptoms that can lead to death. Due to the emergence of antiviral drug-resistant strains, there is an urgent requirement for novel antiviral agents and innovative therapeutic strategies. Using the peptidomimetic ketobenzothiazole protease inhibitor RQAR-Kbt (IN-1, aka N-0100) as a starting point, we report how substituting P2 and P4 positions with natural and unnatural amino acids can modulate the inhibition potency toward matriptase, a prototypical type II transmembrane serine pr...
Source: ChemMedChem - October 21, 2023 Category: Chemistry Authors: Éloïc Colombo Antoine D ésilets Malihe Hassanzadeh Gabriel Lemieux Isabelle Marois Dominic Cliche Julien A Delbrouck Alexandre Murza Fran çois Jean Eric Marsault Martin V Richter Richard Leduc Pierre-Luc Boudreault Source Type: research
Optimization of ketobenzothiazole-based type II transmembrane serine protease inhibitors to block H1N1 influenza virus replication
ChemMedChem. 2023 Oct 21:e202300458. doi: 10.1002/cmdc.202300458. Online ahead of print.ABSTRACTHuman influenza viruses cause acute respiratory symptoms that can lead to death. Due to the emergence of antiviral drug-resistant strains, there is an urgent requirement for novel antiviral agents and innovative therapeutic strategies. Using the peptidomimetic ketobenzothiazole protease inhibitor RQAR-Kbt (IN-1, aka N-0100) as a starting point, we report how substituting P2 and P4 positions with natural and unnatural amino acids can modulate the inhibition potency toward matriptase, a prototypical type II transmembrane serine pr...
Source: ChemMedChem - October 21, 2023 Category: Chemistry Authors: Éloïc Colombo Antoine D ésilets Malihe Hassanzadeh Gabriel Lemieux Isabelle Marois Dominic Cliche Julien A Delbrouck Alexandre Murza Fran çois Jean Eric Marsault Martin V Richter Richard Leduc Pierre-Luc Boudreault Source Type: research
Discovery of ICOS-targeted small molecules using pharmacophore-based screening
This study represents the development and validation of a virtual screening strategy to identify small molecules that bind a novel druggable binding pocket in human ICOS. We used a lipophilic canyon in the apo-structure of ICOS and the ICOS/ICOS-L interface individually as templates for molecular dynamics simulation to generate 3D pharmacophores subsequently used for virtual screening campaigns. Our strategy was successful finding a first-in-class small molecule ICOS binder (5P, KD value = 108.08 ± 26.76 µM) and validating biophysical screening platforms for ICOS-targeted small molecules. We anticipate that future struct...
Source: ChemMedChem - October 16, 2023 Category: Chemistry Authors: Laura Calvo-Barreiro Valerij Talagayev Szymon Pach Somaya A Abdel-Rahman Gerhard Wolber Moustafa Gabr Source Type: research
Structural Optimization of Antimycobacterial Azaaurones Towards Improved Solubility and Metabolic Stability
ChemMedChem. 2023 Oct 16:e202300410. doi: 10.1002/cmdc.202300410. Online ahead of print.ABSTRACTWhile N-acetyl azaaurones have already been disclosed for their potential against tuberculosis (TB), their low metabolic stability remains an unaddressed liability. We now report a study designed to improve the metabolic stability and solubility of the azaaurone scaffold and to identify the structural requirements for antimycobacterial activity. Replacing the N-acetyl moiety for a N-carbamoyl group led to analogues with sub- and nanomolar potencies against M. tuberculosis H37Rv, as well as equipotent against drug-susceptible and...
Source: ChemMedChem - October 16, 2023 Category: Chemistry Authors: Andr é Campaniço Shrika G Harjivan Elisabete Freitas Marco Serafini Manuela M Gaspar Rita Capela Pedro Gomes Audrey Jordaan Ana M Madureira V ânia André Andreia B Silva M Teresa Duarte Isabel Portugal Jo ão Perdigão Rui Moreira Digby F Warner Franci Source Type: research
