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BioChem
Volume 5
Issue 1
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BioChem, Volume 5, Issue 1 (March 2025) – 4 articles

Cover Story (view full-size image): Cancers are still a leading cause of death worldwide. A newly identified subclass of flavonoids, dimeric flavonoids, have sparked scientific interest due to their anticancer activity. Several studies have characterized the potential anticancer activity of dimeric flavonoids as compounds that disrupt the hallmark features, causing cell cycle arrest, inducing apoptosis, inhibiting angiogenesis, suppressing invasion, leading to anti-inflammatory/immunoregulatory effects, and inhibiting the effects of proinflammatory enzymes. The general findings in this review highlight the great potential of applying dimeric compounds in cancer therapy, due to their availability in nature, possible laboratory restructuring, and interaction with chemotherapeutic drugs either by reducing toxicity levels or amplifying their action and combating their associated resistance. View this paper
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25 pages, 2573 KiB  
Article
Overproduction of Phenolic Compounds in Pseudomonas putida KT2440 Through Endogen Deregulation of the Shikimate Pathway
by William Merre, Ricardo Andrade, Cyril Perot, Alexia Chandor-Proust and Caroline Ranquet
BioChem 2025, 5(1), 4; https://doi.org/10.3390/biochem5010004 - 11 Mar 2025
Viewed by 540
Abstract
Metabolic engineering of the shikimate pathway offers a promising strategy for enhancing the production of aromatic compounds in microbial hosts. However, feedback inhibition of key enzymes, such as the 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHP synthase), often limits the yield of target products. In this [...] Read more.
Metabolic engineering of the shikimate pathway offers a promising strategy for enhancing the production of aromatic compounds in microbial hosts. However, feedback inhibition of key enzymes, such as the 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHP synthase), often limits the yield of target products. In this study, we focused on the DAHP synthase (AroF-I) from Pseudomonas putida. Through computational modeling and experimental validation, we identified specific amino-acid residues responsible for tyrosine-mediated feedback inhibition. By targeted mutagenesis, we engineered DAHP synthase variants that exhibit reduced sensitivity to feedback inhibition. The introduction of these engineered enzymes into a metabolically engineered Pseudomonas putida strain resulted in significantly increased production of p-coumaric acid. Our findings provide valuable insights into the regulation of the shikimate pathway and demonstrate the potential of protein engineering to improve microbial production of aromatic compounds. Full article
(This article belongs to the Special Issue Feature Papers in BioChem)
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21 pages, 2121 KiB  
Review
Therapeutic Management of Ebola Virus: Targeting Oxidative Stress and Inflammatory Pathways
by Martin Ndayambaje, Hicham Wahnou, Abdallah Naya and Mounia Oudghiri
BioChem 2025, 5(1), 3; https://doi.org/10.3390/biochem5010003 - 11 Feb 2025
Viewed by 793
Abstract
The Ebola virus (EBOV), a highly lethal pathogen causing hemorrhagic fever, poses a persistent public health threat, with devastating multi-organ complications and high transmission potential through bodily fluids. EBOV’s pathogenesis is marked by severe oxidative stress and immune dysregulation, where increased reactive oxygen [...] Read more.
The Ebola virus (EBOV), a highly lethal pathogen causing hemorrhagic fever, poses a persistent public health threat, with devastating multi-organ complications and high transmission potential through bodily fluids. EBOV’s pathogenesis is marked by severe oxidative stress and immune dysregulation, where increased reactive oxygen species (ROS) levels foster cellular damage, hinder immune defenses, and facilitate viral replication. Through immune evasion and suppression of cellular stress responses, EBOV affects both innate and adaptive immunity, activating pyroptosis, PANoptosis, necroptosis, and lymphocyte apoptosis, thereby amplifying inflammation and disease severity. Recent research suggests that bioactive molecules, including quercetin, curcumin, eugenol, and p-anisaldehyde, may offer therapeutic potential due to their antioxidant, anti-inflammatory, and immunomodulatory effects. This review also underscores the potential of conventional treatments, including amiodarone, favipiravir, remdesivir, azithromycin, chloroquine, and nitazoxanide, as therapeutic agents against EBOV, thanks to their antiviral and anti-inflammatory properties, although their efficacy varies across experimental models. These natural compounds could enhance immune resilience by scavenging ROS, modulating inflammation, and mitigating immune dysregulation, presenting promising adjunctive strategies to support conventional EBOV therapies. Full article
(This article belongs to the Special Issue Targeting Oxidative Stress and Inflammation: Emerging Mechanisms and Therapeutics)
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18 pages, 724 KiB  
Review
An Overview of the Therapeutic Potential of Dimeric Flavonoids for Targeting Cancer Hallmarks
by Inês Lopes, Isabel Meireles, Rafaela Rocha, Rui Medeiros and Fátima Cerqueira
BioChem 2025, 5(1), 2; https://doi.org/10.3390/biochem5010002 - 14 Jan 2025
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Abstract
Evidence found in the literature indicates that dimeric flavonoids constitute important therapeutic options against cancer. Using these molecules to prevent cancer progression might be a novel and promising therapeutic approach with advantages like fewer side effects, easy access in nature, overall health benefits [...] Read more.
Evidence found in the literature indicates that dimeric flavonoids constitute important therapeutic options against cancer. Using these molecules to prevent cancer progression might be a novel and promising therapeutic approach with advantages like fewer side effects, easy access in nature, overall health benefits and overcoming drug resistance. Cancer is a complex disease and still not understood, but there are some common mechanisms and biological characteristics underlying tumor progression that have been scrutinized over the years. This information was summarized in a conceptual framework designated as hallmarks of cancer. Dimeric flavonoids exert biological effects in several pathways involved in cancer hallmarks including cell growth, cell cycle, apoptosis, metastasis and metabolism. Full article
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17 pages, 1395 KiB  
Article
Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents
by Matthew J. A. Phillips, Alison T. Ung, Elizabeth J. Harry, Jason Ashmore and Andrew M. McDonagh
BioChem 2025, 5(1), 1; https://doi.org/10.3390/biochem5010001 - 31 Dec 2024
Viewed by 845
Abstract
Isoquinoline derivatives exhibit a range of biological properties, including antibacterial activity, and are thus attractive as a scaffold for developing broad-spectrum antibacterial compounds. A series of six isoquinoline-based compounds were synthesized using the reaction of 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline with dimethyl acetylenedicarboxylate (DMAD) to provide the [...] Read more.
Isoquinoline derivatives exhibit a range of biological properties, including antibacterial activity, and are thus attractive as a scaffold for developing broad-spectrum antibacterial compounds. A series of six isoquinoline-based compounds were synthesized using the reaction of 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline with dimethyl acetylenedicarboxylate (DMAD) to provide the tricyclic (2Z)-[2-oxo-5,6-dihydropyrrolo[2,1,a]isoquinolin-3-ylidene]-2-ethanoate. The [2 + 3] cycloaddition of DMAD with C-6 and C-7 substituted 1-methyl-3,4-dihydroisoquinolines proceeded using aryl ethers or unsubstituted compounds, but not with amine, amide or nitro moieties at the C-7 position. Compounds 8d and 8f were found to have antibacterial properties against some Gram-positive pathogens (Staphylococcus aureus—8d = 16 µg/mL, 8f = 32 µg/mL; Streptococcus pneumoniae—8f = 32 µg/mL; and Enterococcus faecium—8d = 128 µg/mL, 8f = 64 µg/mL). Evaluation of their cytotoxic properties against mammalian cell lines revealed some cytotoxic effects (8b and 8d, 125 µM, 24 h, HEp-2 cells) and (8a, 8b, 8d = 125 µM, 8f = 62.5 µM, 24 h, McCoy B cells), suggesting limitations in their antibacterial applications without further development. Full article
(This article belongs to the Special Issue Feature Papers in BioChem)
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