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Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Bioorganic Chemistry and Medicinal Chemistry".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 999

Special Issue Editor


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Special Issue Information

Dear Colleagues,

Natural products (NPs) and NP-based semi-synthetic compounds have been attracting increased attention from the scientific community due to their great structural and chemical diversity. Notably, NP-based molecules are valid sources of drug lead compounds, because 60% of chemotherapeutic agents originate from natural products. On the other hand, pseudo‐natural products (PNPs) combine natural product (NP) fragments in novel and intriguing arrangements that are not accessible via biosynthesis pathways. Moreover, they can be regarded as non‐biogenic fusions of NP‐derived fragments. Scientists have established new synthesis principles to advance beyond the chemical space explored by nature by combining the principles of biology-orientated synthesis (BIOS) and fragment-based compound design. Interestingly, scaffolds from different NPs can be combined and reconnected to create new alternative molecular scaffolds: so-called pseudo-natural products.

The aim of this Special Issue on natural product (NP)- and pseudo‐natural product (PNP)-based drug discovery is to underline the most recent discoveries and progress in all fields of biological sciences dealing with NPs and PNPs. This Special Issue will mainly focus on biological studies on NPs and PNPs on a molecular level. In addition, this Special Issue will also focus on the development of new NP- and PNP-based therapeutic agents for the treatment of numerous diseases, employing the newest techniques in pharmacology, biotechnology, and genetic engineering. For this Special Issue, we welcome original articles, communications, and reviews exploring drug discovery and development.

Dr. Hidayat Hussain
Guest Editor

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Keywords

  • natural products
  • pseudo-natural products
  • drug discovery
  • molecular level
  • in vitro studies
  • in vivo studies
  • computational methods
  • mode of action
  • computational methods

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Published Papers (2 papers)

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Research

21 pages, 1652 KB  
Article
Comparative Molecular Profiling and Bioactivity Analysis of Algerian Propolis: Antioxidant, Antibacterial Activities, and In Silico NRF2-KEAP1 Pathway Modulation
by Amel Reguig, Ahmed Messai, Ibtissam Kahina Bedaida, Diana C. G. A. Pinto, Chawki Bensouici, Abdelmoneim Tarek Ouamane, Artur M. S. Silva and Jean-Philippe Roy
Curr. Issues Mol. Biol. 2025, 47(9), 761; https://doi.org/10.3390/cimb47090761 - 15 Sep 2025
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Abstract
Propolis, a natural bee-derived product rich in diverse phytochemicals with potential therapeutic benefits, remains underexplored in Algeria. This study investigated the molecular profile, antioxidant capacity, and antibacterial activity of propolis sourced from two bioclimatically distinct Algerian regions (humid subtropical Batna and hot desert [...] Read more.
Propolis, a natural bee-derived product rich in diverse phytochemicals with potential therapeutic benefits, remains underexplored in Algeria. This study investigated the molecular profile, antioxidant capacity, and antibacterial activity of propolis sourced from two bioclimatically distinct Algerian regions (humid subtropical Batna and hot desert Biskra) using electrospray ionization mass spectrometry, ultra-high-performance liquid chromatography with diode array detection, and gas chromatography–mass spectrometry. Significant regional variations were observed, with propolis extract 2 (PE2) exhibiting a higher bioactive content, including a constituent not previously reported in propolis. Antioxidant assays (2,2-diphenyl-1-picrylhydrazyl, 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), ferric reducing antioxidant power, and phenanthroline) demonstrated that PE2 consistently outperformed propolis extract 1 and the reference standards (DPPH IC50: 27.74 µg/mL; FRAP: 5.16 µg/mL). Antibacterial testing demonstrated potent bactericidal effects, particularly for PE2, with minimum inhibitory concentration values equivalent to the minimum bactericidal concentrations required against Staphylococcus aureus ATCC 25923 (18.75 µg/mL) and Escherichia coli ATCC 25922 (133 µg/mL). Molecular docking identified nine bioactive compounds with high KEAP1 binding affinity, with 1,3-O-caffeoyl-dihydrocaffeoylglycerol (first time reported in propolis) showing the strongest binding affinity (−11.02 Kcal/mol). In silico pharmacokinetic predictions further verified its drug-like properties. These findings suggest the tested Algerian propolis samples, as a source of natural alternative antioxidants and antimicrobials, provide a basis for future research in drug discovery and development. Full article
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9 pages, 635 KB  
Article
Osteogenic Potential of Osteolforte: Gene and Protein-Level Evaluation in Human Bone Marrow Stromal Cells
by Da-Sol Kim, Soo-Kyung Bae, Yeon-Ju Kwak, Geum-Joung Youn and Hye-Ock Jang
Curr. Issues Mol. Biol. 2025, 47(8), 588; https://doi.org/10.3390/cimb47080588 - 24 Jul 2025
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Abstract
Osteolforte, a compound with potential bone-regenerative properties, was investigated for its effects on human bone marrow stromal cells (hBMSCs). This study aimed to evaluate its impact on cell viability, osteogenic differentiation, and both gene and protein expression using a combination of assays, [...] Read more.
Osteolforte, a compound with potential bone-regenerative properties, was investigated for its effects on human bone marrow stromal cells (hBMSCs). This study aimed to evaluate its impact on cell viability, osteogenic differentiation, and both gene and protein expression using a combination of assays, including CCK-8, Alizarin Red S staining, Quantitative Real-Time PCR (qRT-PCR), and Western blot analysis. The results demonstrated that Osteolforte significantly enhanced osteogenic differentiation in hBMSCs. Alizarin Red S staining revealed increased mineralization, indicating elevated calcium deposition. Gene expression analysis showed an upregulation of key osteogenic markers, including runt-related transcription factor-2 (RUNX-2), collagen type I (COL-1), and bone morphogenetic protein-2 (BMP-2), supporting the role of Osteolforte in promoting osteoblastic activity. In particular, the elevated expression of RUNX-2—a master transcription factor in osteoblast differentiation along with COL-1, a major bone matrix component, and BMP-2, a key bone morphogenetic protein—highlights the compound’s osteogenic potential. In conclusion, Osteolforte enhances early-stage osteogenesis and mineralization in hBMSCs and represents a promising candidate for bone regeneration. Full article
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