Naturally occurring of α,β-diepoxy-containing compounds: origin, structures, and biological activities

Vil, Vera A.; Gloriozova, Tatyana A.; Poroikov, Vladimir; Terent’ev, Alexander O.; Savidov, Nick; Dembitsky, Valery M.

doi:10.1007/s00253-019-09711-4

Cited by 17 publications

(21 citation statements)

References 107 publications

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“…3lp-10 [ 18 , 19 ] and became a focus of scientific interest because of its anticancer activity [ 18 , 20 ]. A recent survey on the meta-level highlighted the enormous pharmaceutical potential of di-epoxic compounds such as xanthoepocin as these metabolites show a wide bioactivity spectrum [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Xanthoepocin, a photolabile antibiotic of Penicillium ochrochloron CBS 123823 with high activity against multiresistant gram-positive bacteria

et al. 2022

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Background With the steady increase of antibiotic resistance, several strategies have been proposed in the scientific community to overcome the crisis. One of many successful strategies is the re-evaluation of known compounds, which have been early discarded out of the pipeline, with state-of-the-art know-how. Xanthoepocin, a polyketide widespread among the genus Penicillium with an interesting bioactivity spectrum against gram-positive bacteria, is such a discarded antibiotic. The purpose of this work was to (i) isolate larger quantities of this metabolite and chemically re-evaluate it with modern technology, (ii) to explore which factors lead to xanthoepocin biosynthesis in P. ochrochloron, and (iii) to test if it is beside its known activity against methicillin-resistant Staphylococcus aureus (MRSA), also active against linezolid and vancomycin-resistant Enterococcus faecium (LVRE)—a very problematic resistant bacterium which is currently on the rise. Results In this work, we developed several new protocols to isolate, extract, and quantify xanthoepocin out of bioreactor batch and petri dish-grown mycelium of P. ochrochloron. The (photo)chemical re-evaluation with state-of-the-art techniques revealed that xanthoepocin is a photolabile molecule, which produces singlet oxygen under blue light irradiation. The intracellular xanthoepocin content, which was highest under ammonium-limited conditions, varied considerably with the applied irradiation conditions in petri dish and bioreactor batch cultures. Using light-protecting measures, we achieved MIC values against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), which were up to 5 times lower than previously published. In addition, xanthoepocin was highly active against a clinical isolate of linezolid and vancomycin-resistant Enterococcus faecium (LVRE). Conclusions This interdisciplinary work underlines that the re-evaluation of known compounds with state-of-the-art techniques is an important strategy in the combat against multiresistant bacteria and that light is a crucial factor on many levels that needs to receive more attention. With appropriate light protecting measures in the susceptibility tests, xanthoepocin proved to be a powerful antibiotic against MRSA and LVRE. Exploring the light response of other polyketides may be pivotal for re-introducing previously discarded metabolites into the antibiotic pipeline and to identify photosensitizers which might be used for (antimicrobial) photodynamic therapies.

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Section: Introductionmentioning

confidence: 99%

Xanthoepocin, a photolabile antibiotic of Penicillium ochrochloron CBS 123823 with high activity against multiresistant gram-positive bacteria

et al. 2022

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“…Both compounds showed potent cytotoxic activities against human cervical cancer cell lines (HeLa) and human gastric cancer cells (BGC 823) [81]. The rare ring-A seco-cycloartane carbon skeleton, coronalolide methyl ester (39), and methyl coronalolate acetate (40) were isolated from the leaves and stems of Gardenia coronaria. Both compounds showed broad cytotoxic activity when evaluated against a panel of human cancer cell lines [82].…”

Section: Cyclopropane Containing Steroids and Triterpenoidsmentioning

confidence: 99%

Antitumor Profile of Carbon-Bridged Steroids (CBS) and Triterpenoids

2021

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This review focuses on the rare group of carbon-bridged steroids (CBS) and triterpenoids found in various natural sources such as green, yellow-green, and red algae, marine sponges, soft corals, ascidians, starfish, and other marine invertebrates. In addition, this group of rare lipids is found in amoebas, fungi, fungal endophytes, and plants. For convenience, the presented CBS and triterpenoids are divided into four groups, which include: (a) CBS and triterpenoids containing a cyclopropane group; (b) CBS and triterpenoids with cyclopropane ring in the side chain; (c) CBS and triterpenoids containing a cyclobutane group; (d) CBS and triterpenoids containing cyclopentane, cyclohexane or cycloheptane moieties. For the comparative characterization of the antitumor profile, we have added several semi- and synthetic CBS and triterpenoids, with various additional rings, to identify possible promising sources for pharmacologists and the pharmaceutical industry. About 300 CBS and triterpenoids are presented in this review, which demonstrate a wide range of biological activities, but the most pronounced antitumor profile. The review summarizes biological activities both determined experimentally and estimated using the well-known PASS software. According to the data obtained, two-thirds of CBS and triterpenoids show moderate activity levels with a confidence level of 70 to 90%; however, one third of these lipids demonstrate strong antitumor activity with a confidence level exceeding 90%. Several CBS and triterpenoids, from different lipid groups, demonstrate selective action on different types of tumor cells such as renal cancer, sarcoma, pancreatic cancer, prostate cancer, lymphocytic leukemia, myeloid leukemia, liver cancer, and genitourinary cancer with varying degrees of confidence. In addition, the review presents graphical images of the antitumor profile of both individual CBS and triterpenoids groups and individual compounds.

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“…Fungi, fungal endophytes, myxomycetes, and the lichenized Ascomycetes are of great interest to pharmacologists and chemists, since they produce many biologically active substances, such as aromatic and phenolic compounds, tannins, hydrocarbons, lipids, unusual steroids, triterpenoids, heterocyclic compounds, peptides, and polycyclic endoperoxides [ 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ].…”

Section: Polycyclic Endoperoxides Derived From Fungi and Fungal Enmentioning

confidence: 99%

Antiprotozoal and Antitumor Activity of Natural Polycyclic Endoperoxides: Origin, Structures and Biological Activity

et al. 2021

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Polycyclic endoperoxides are rare natural metabolites found and isolated in plants, fungi, and marine invertebrates. The purpose of this review is a comparative analysis of the pharmacological potential of these natural products. According to PASS (Prediction of Activity Spectra for Substances) estimates, they are more likely to exhibit antiprotozoal and antitumor properties. Some of them are now widely used in clinical medicine. All polycyclic endoperoxides presented in this article demonstrate antiprotozoal activity and can be divided into three groups. The third group includes endoperoxides, which show weak antiprotozoal activity with a reliability of up to 70%, and this group includes only 1.1% of metabolites. The second group includes the largest number of endoperoxides, which are 65% and show average antiprotozoal activity with a confidence level of 70 to 90%. Lastly, the third group includes endoperoxides, which are 33.9% and show strong antiprotozoal activity with a confidence level of 90 to 99.6%. Interestingly, artemisinin and its analogs show strong antiprotozoal activity with 79 to 99.6% confidence against obligate intracellular parasites which belong to the genera Plasmodium, Toxoplasma, Leishmania, and Coccidia. In addition to antiprotozoal activities, polycyclic endoperoxides show antitumor activity in the proportion: 4.6% show weak activity with a reliability of up to 70%, 65.6% show an average activity with a reliability of 70 to 90%, and 29.8% show strong activity with a reliability of 90 to 98.3%. It should also be noted that some polycyclic endoperoxides, in addition to antiprotozoal and antitumor properties, show other strong activities with a confidence level of 90 to 97%. These include antifungal activity against the genera Aspergillus, Candida, and Cryptococcus, as well as anti-inflammatory activity. This review provides insights on further utilization of polycyclic endoperoxides by medicinal chemists, pharmacologists, and the pharmaceutical industry.

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Naturally occurring of α,β-diepoxy-containing compounds: origin, structures, and biological activities

Cited by 17 publications

References 107 publications

Xanthoepocin, a photolabile antibiotic of Penicillium ochrochloron CBS 123823 with high activity against multiresistant gram-positive bacteria

Xanthoepocin, a photolabile antibiotic of Penicillium ochrochloron CBS 123823 with high activity against multiresistant gram-positive bacteria

Antitumor Profile of Carbon-Bridged Steroids (CBS) and Triterpenoids

Antiprotozoal and Antitumor Activity of Natural Polycyclic Endoperoxides: Origin, Structures and Biological Activity

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