Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities. Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.

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Natural products in drug discovery: advances and opportunities.

Comprehensive Natural Products Chemistry

Mycogenic synthesis of medically applied zinc oxide (ZnO) and copper oxide (CuO) nanoparticles (NPs) were exploited using Penicillium chrysogenum. The biogenesis and capping processes of the produced nano-metals were conducted by functional fungal extracellular enzymes and proteins. The obtained ZnO-NPs and CuO-NPs were characterized. Also, the antibacterial activity and minimum inhibitory concentration (MIC) values of ZnO-NPs and CuO-NPs were determined. Also, antibiofilm and antifungal activities were investigated. Results have demonstrated the ability of the bio-secreted proteins to cape and reduce ZnO and CuO to hexagonal and spherical ZnO-NPs and CuO-NPs with particle size at 9.0–35.0 nm and 10.5–59.7 nm, respectively. Both ZnO-NPs and CuO-NPs showed high antimicrobial activities not only against Gram-positive and Gram-negative bacteria but also against some phytopathogenic fungal strains. Besides this, those NPs showed varied antibiofilm effects against different microorganisms. Quantitative and qualitative analyses indicated that CuO-NPs had an effective antibiofilm activity against Staphylococcus aureus and therefore can be applied in diverse medical devices. Thus, the mycogenic green synthesized ZnO-NPs and CuO-NPs have the potential as smart nano-materials to be used in the medical field to limit the spread of some pathogenic microbes.

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Eco-friendly Mycogenic Synthesis of ZnO and CuO Nanoparticles for In Vitro Antibacterial, Antibiofilm, and Antifungal Applications

Ecofriendly novel synthesis of tertiary composite based on cellulose and myco-synthesized selenium nanoparticles: Characterization, antibiofilm and biocompatibility.

Over a long period of time, humans have explored many natural resources looking for remedies of various ailments. Traditional medicines have played an intrinsic role in human life for thousands of years, with people depending on medicinal plants and their products as dietary supplements as well as using them therapeutically for treatment of chronic disorders, such as cancer, malaria, diabetes, arthritis, inflammation, and liver and cardiac disorders. However, plant resources are not sufficient for treatment of recently emerging diseases. In addition, the seasonal availability and other political factors put constrains on some rare plant species. The actual breakthrough in drug discovery came concurrently with the discovery of penicillin from Penicillium notatum in 1929. This discovery dramatically changed the research of natural products and positioned microbial natural products as one of the most important clues in drug discovery due to availability, variability, great biodiversity, unique structures, and the bioactivities produced. The number of commercially available therapeutically active compounds from microbial sources to date exceeds those discovered from other sources. In this review, we introduce a short history of microbial drug discovery as well as certain features and recent research approaches, specifying the microbial origin, their featured molecules, and the diversity of the producing species. Moreover, we discuss some bioactivities as well as new approaches and trends in research in this field.

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Microbial Natural Products in Drug Discovery

Over the last decades, endophytic fungi represent a new source of pharmacologically active secondary metabolites based on the underlying assumption that they live symbiotically within their plant host. In the present study, a new endophytic fungus was isolated from Rauwolfia macrophylla, a medicinal plant from Cameroon. The fungus showed a highest homology to Curvularia sp. based on complete nucleotide sequence data generated from the internal transcribed spacer (ITS) of ribosomal DNA region. Large scale fermentation, working-up and separation of the strain extract using different chromatographic techniques afforded three bioactive compounds: 2'-deoxyribolactone (1), hexylitaconic acid (2) and ergosterol (3). The chemical structures of compounds 1-3 were confirmed by 1 and 2D NMR spectroscopy and mass spectrometry, and comparison with corresponding literature data. Biologically, the antimicrobial, antioxidant activities and the acetylcholinesterase inhibitory of the isolated compounds were studied.

Bioactive secondary metabolites from new endophytic fungus Curvularia. sp isolated from Rauwolfia macrophylla

Meleagrin from marine fungus Emericella dentata Nq45: crystal structure and diverse biological activity studies.

Uracil derivatives have a great attraction because they play an important role in pharmacological activities. Pyrimidodiazepines, lumazines, triazolopyrimidines and xanthines have significant wide spectrum activities including anticancer, antiviral as well as antimicrobial activities. A newly synthesized compounds pyrimido[4,5-b][1, 4]diazepines 5a–e, 6a–d, lumazines 7a–d, triazolo[4,5-d]pyrimidine 8 and xanthines 9, 10 was prepared in a good yields. The antimicrobial and antioxidant activities of compounds 5a, 5b, 6a, 6d and 8 exhibited a wide range activity against the pathogenic tested microbes (Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans, and Saccharomyces cerevisiae). Compound 8 showed activity against the fungus Aspergillus niger. The highest antioxidant activity was noticed for compound 5a. A series of novel pyrimido[4,5-b][1, 4]diazepines 5a–e, 6a–d, lumazines 7a–d, triazolo[4,5-d]pyrimidine 8 and xanthines 9, 10 was prepared from 5,6-diamino-1-(2-chlorobenzyl)uracil 3 in good yields. Compounds 5a–e, 6a–d were prepared by sequential manipulation of 3 with α,β-unsaturated ketones. Lumazines 7a–d were obtained from 3 by treatment with phenacyl bromides in the presence of TEA. Compound 8 was prepared by treatment of 3 with HNO2, while xanthines 9, 10 were obtained from 3 by consecutive acetylation then intramolecular cyclodehydration or heating with malononitrile under solvent-free condition. The antimicrobial and antioxidant activity of this series was evaluated in vitro and they showed either weak or moderate activities.

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One pot synthesis, antimicrobial and antioxidant activities of fused uracils: pyrimidodiazepines, lumazines, triazolouracil and xanthines

Terretonin N (1), a new highly oxygenated and unique tetracyclic 6-hydroxymeroterpenoid, was isolated together with seven known compounds from the ethyl acetate extract of a solid-state fermented culture of Nocardiopsis sp. Their structures were elucidated by spectroscopic analysis. The structure and absolute configuration of 1 were unambiguously determined by X-ray crystallography. The isolation and taxonomic characterization of Nocardiopsis sp. is reported. The antimicrobial activity and cytotoxicity of the strain extract and compound 1 were studied using different microorganisms and a cervix carcinoma cell line, respectively.

Ahmed S. Abdel-Razek

Papers

Microbial Natural Products in Drug Discovery

Bioactive secondary metabolites from new endophytic fungus Curvularia. sp isolated from Rauwolfia macrophylla

Meleagrin from marine fungus Emericella dentata Nq45: crystal structure and diverse biological activity studies.

One pot synthesis, antimicrobial and antioxidant activities of fused uracils: pyrimidodiazepines, lumazines, triazolouracil and xanthines

Terretonin N: A New Meroterpenoid from Nocardiopsis sp.