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Phytochemistry Nov 2022Developing highly effective HIV latency-reversing agent is an inportmant approach for the treatment of AIDS via the "shock and kill" of latent HIV. In this study, two...
Developing highly effective HIV latency-reversing agent is an inportmant approach for the treatment of AIDS via the "shock and kill" of latent HIV. In this study, two unreported modified daphnane-type diterpenes (chamaedaphnelide A and epi-chamaedaphnelide A) and one unreported tigliane-type diterpene (chamaedaphnelide B), along with four known daphnane-type diterpenes and one known tigliane-type diterpene were obtained from the leaves of Wikstroemia chamaedaphne. Chamaedaphnelide A and epi-chamaedaphnelide A represents the first A ring cleavage daphnane-type backbone. Chamaedaphnelide A, epi-chamaedaphnelide A, chamaedaphnelide B, and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate showed HIV latency-reversing activity, especially chamaedaphnelide B and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate displayed equally potential to positive drugs prostratin with reversing latent HIV on more than 100-fold compared to unstimulated cells. Furthermore, the activation of STAT1 was involved in the HIV latency-reversing activity of these diterpenes, firstly demonstrating that daphnane- and tigliane-type diterpenes can rapidly activate STAT1 activity. Indeed, these results also supported that activating STAT1 activity is a pathway for reversing latent HIV.
Topics: Anti-HIV Agents; Diterpenes; HIV; HIV Infections; Humans; Plant Leaves; STAT1 Transcription Factor; Virus Latency; Wikstroemia
PubMed: 36027969
DOI: 10.1016/j.phytochem.2022.113395 -
Bioorganic & Medicinal Chemistry Letters Nov 2020Hispanolone is a furolabdane diterpene isolated from Ballota hispanica, whose natural product chemistry has been summarized and updated here, including several aspects... (Review)
Review
Hispanolone is a furolabdane diterpene isolated from Ballota hispanica, whose natural product chemistry has been summarized and updated here, including several aspects associated with the isolation, structure determination, hemisynthesis, total synthesis, and pharmacology, and related hispanolone diterpenoids that have attracted the interest of different laboratories from diverse perspective and expertise in the last forty-two years.
Topics: Anti-Bacterial Agents; Antineoplastic Agents, Phytogenic; Ballota; Biological Products; Diterpenes; Enzyme Inhibitors; Humans; Molecular Conformation
PubMed: 32818604
DOI: 10.1016/j.bmcl.2020.127498 -
Phytochemistry Oct 2022The Phytochemical profiling of the root extract of Salvia leriifolia, an endemic plant of Iran, was investigated and 16 abietane diterpenes were isolated, and three were...
The Phytochemical profiling of the root extract of Salvia leriifolia, an endemic plant of Iran, was investigated and 16 abietane diterpenes were isolated, and three were original compounds. 1D and 2D NMR and HRMS performed structural elucidation. The absolute configuration of the previously unreported compounds was determined by circular dichroism (ECD). The cytotoxicity of the isolated compounds was investigated against AGS, MIA PaCa-2, HeLa, and MCF-7 cell lines by the MTT assay. The known diterpene pisiferal possesses high cytotoxicity against all investigated cell lines at a concentration between 9.3 ± 0.6 and 14.38 ± 1.4 μM.
Topics: Abietanes; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Diterpenes; Humans; Molecular Structure; Salvia
PubMed: 35863476
DOI: 10.1016/j.phytochem.2022.113310 -
Journal of Natural Medicines Sep 2023Tigliane and daphnane diterpenoids are characteristically distributed in plants of the Thymelaeaceae family as well as the Euphorbiaceae family and are structurally... (Review)
Review
Tigliane and daphnane diterpenoids are characteristically distributed in plants of the Thymelaeaceae family as well as the Euphorbiaceae family and are structurally diverse due to the presence of polyoxygenated functionalities in the polycyclic skeleton. These diterpenoids are known as toxic components, while they have been shown to exhibit a wide variety of biological activities, such as anti-cancer, anti-HIV, and analgesic activity, and are attracting attention in the field of natural product drug discovery. This review focuses on naturally occurring tigliane and daphnane diterpenoids from plants of the Thymelaeaceae family and provides an overview of their chemical structure, distribution, isolation, structure determination, chemical synthesis, and biological activities, with a prime focus on the recent findings.
Topics: Phorbols; Thymelaeaceae; Diterpenes; Drug Discovery; Molecular Structure
PubMed: 37294498
DOI: 10.1007/s11418-023-01713-x -
Chemistry & Biodiversity Mar 2023Five new ent-pimarane diterpenes (1-5) and five known analogs (6-10) were isolated from the aerial parts of Siegesbeckia pubescens. Their structures, including absolute...
Five new ent-pimarane diterpenes (1-5) and five known analogs (6-10) were isolated from the aerial parts of Siegesbeckia pubescens. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially 1D and 2D NMR and quantum chemical electronic circular dichroism calculations. All the isolated compounds were evaluated for their cytotoxicity against human BT549, A549 and H157 cancer cell lines. Among them, compounds 1 and 2 showed mild cytotoxicity against lung cancer cell lines H157 with IC values of 16.35±2.59 and 18.86±4.83 μM, respectively.
Topics: Humans; Abietanes; Diterpenes; Molecular Structure; Plant Components, Aerial; Sigesbeckia
PubMed: 36728645
DOI: 10.1002/cbdv.202201090 -
Marine Drugs Mar 2021Novel drug leads for malaria therapy are urgently needed because of the widespread emergence of resistance to all available drugs. Screening of the Harbor Branch...
Novel drug leads for malaria therapy are urgently needed because of the widespread emergence of resistance to all available drugs. Screening of the Harbor Branch enriched fraction library against the chloroquine-resistant strain (Dd2) followed by bioassay-guided fractionation led to the identification of two potent antiplasmodials; a novel diterpene designated as bebrycin A () and the known C21 degraded terpene nitenin (). A SYBR Green I assay was used to establish a Dd2 EC of 1.08 ± 0.21 and 0.29 ± 0.02 µM for bebrycin A and nitenin, respectively. Further analysis was then performed to assess the stage specificity of the inhibitors antiplasmodial effects on the Dd2 intraerythrocytic life cycle. Exposure to bebrycin A was found to block parasite maturation at the schizont stage if added any time prior to late schizogony at 42 hours post invasion, (HPI). In contrast, early life cycle exposure to nitenin (prior to 18 HPI) was identified as crucial to parasite inhibition, suggesting nitenin may target the maturation of the parasite during the transition from ring to early trophozoite (6-18 HPI), a novel property among known antimalarials.
Topics: Animals; Anthozoa; Antimalarials; Diterpenes; Hep G2 Cells; Humans; Life Cycle Stages; Malaria, Falciparum; Molecular Structure; Plasmodium falciparum; Porifera; Structure-Activity Relationship; Time Factors
PubMed: 33805935
DOI: 10.3390/md19040179 -
Molecules (Basel, Switzerland) Oct 2019Lamiaceae is one of the largest families of angiosperms and is classified into 12 subfamilies that are composed of 295 genera and 7775 species. It presents a variety of...
Lamiaceae is one of the largest families of angiosperms and is classified into 12 subfamilies that are composed of 295 genera and 7775 species. It presents a variety of secondary metabolites such as diterpenes that are commonly found in their species, and some of them are known to be chemotaxonomic markers. The aim of this work was to construct a database of diterpenes and to use it to perform a chemotaxonomic analysis among the subfamilies of Lamiaceae, using molecular descriptors and self-organizing maps (SOMs). The 4115 different diterpenes corresponding to 6386 botanical occurrences, which are distributed in eight subfamilies, 66 genera, 639 different species and 4880 geographical locations, were added to SistematX. Molecular descriptors of diterpenes and their respective botanical occurrences were used to generate the SOMs. In all obtained maps, a match rate higher than 80% was observed, demonstrating a separation of the Lamiaceae subfamilies, corroborating with the morphological and molecular data proposed by Li et al. Therefore, through this chemotaxonomic study, we can predict the localization of a diterpene in a subfamily and assist in the search for secondary metabolites with specific structural characteristics, such as compounds with potential biological activity.
Topics: Algorithms; Bioprospecting; Databases as Topic; Diterpenes; Lamiaceae; Machine Learning; Phylogeny
PubMed: 31671588
DOI: 10.3390/molecules24213908 -
Journal of Natural Products May 2023Laeviganoids A-T (-), 20 new -clerodane-type diterpenoids featuring a 2-furanone (-) or a furan (-) ring, as well as six analogues (-), were isolated from the roots of ....
Laeviganoids A-T (-), 20 new -clerodane-type diterpenoids featuring a 2-furanone (-) or a furan (-) ring, as well as six analogues (-), were isolated from the roots of . Their structures were determined by spectroscopic data analysis, experimental electronic circular dichroism measurements, and X-ray crystallographic studies. Compounds -, , -, and could influence the anti-inflammatory protumoral phenotype of macrophages. Among these compounds, and are the most potent, as evidenced by consistently downregulating the classic anti-inflammatory cytokine IL-10 and upregulating the classic pro-inflammatory cytokine TNF-α on the secretion level in RAW 264.7 cells.
Topics: Animals; Mice; Diterpenes, Clerodane; Croton; Molecular Structure; Diterpenes; Anti-Inflammatory Agents; RAW 264.7 Cells
PubMed: 37159431
DOI: 10.1021/acs.jnatprod.3c00173 -
Molecules (Basel, Switzerland) May 2022Three isopimarane diterpenes [fladins B (), C (), and D ()] were isolated from the twigs and leaves of Chinese folk medicine, . The chemical structures were determined...
Three isopimarane diterpenes [fladins B (), C (), and D ()] were isolated from the twigs and leaves of Chinese folk medicine, . The chemical structures were determined by the analysis of the comprehensive spectroscopic data, and the absolute configuration was confirmed by X-ray crystallographic analysis. The structures of - were formed from isopimaranes through the rearrangement of ring A by the bond break at C-3 and C-4 to form a new -lactone ring system between C-3 and C-9. This structure type represents the first discovery of a natural isopimarane diterpene with an unusual lactone moiety at C-9 and C-10. In the crystal of , molecules are linked to each other by intermolecular O-H···O bonds, forming chains along the axis. Compounds - were evaluated for their bioactivities against different diseases. None of these compounds displayed cytotoxic activities against HCT116 and A549 cancer cell lines, antifungal activities against and , or antiviral activities against HIV entry at 20 µg/mL (62.9-66.7) µM. Compounds and did not show antiviral activities against Ebola entry at 20 µg/mL either; only was found to show an 81% inhibitory effect against Ebola entry activity at 20 µg/mL (66.7 µM). The bioactivity evidence suggested that this type of compound could be a valuable antiviral lead for further structure modification to improve the antiviral potential.
Topics: Abietanes; Antiviral Agents; Diterpenes; Hemorrhagic Fever, Ebola; Isodon; Lactones; Plant Leaves
PubMed: 35630575
DOI: 10.3390/molecules27103098 -
Phytomedicine : International Journal... Jul 2024The African continent is home to five biodiversity hotspots, boasting an immense wealth of medicinal flora, fungi and marine life. Diterpenes extracted from such natural... (Review)
Review
BACKGROUND
The African continent is home to five biodiversity hotspots, boasting an immense wealth of medicinal flora, fungi and marine life. Diterpenes extracted from such natural products have compelling cytotoxic activities that warrant further exploration for the drug market, particularly in cancer therapy, where mortality rates remain elevated worldwide.
PURPOSE
To demonstrate the potential of African natural products on the global stage for cancer therapy development and provide an in-depth analysis of the current literature on the activity of cancer cytotoxic diterpenes from African natural sources (to our knowledge, the first of its kind); not only to reveal the most promising candidates for clinical development, but to demonstrate the importance of preserving the threatened ecosystems of Africa.
METHODS
A comprehensive search by means of the PRISMA strategy was conducted using electronic databases, namely Web of Science, PubMed, Google Scholar and ScienceDirect. The search terms employed were 'diterpene & mechanism & cancer' and 'diterpene & clinical & cancer'. The selection process involved assessing titles in English, Portuguese and Spanish, adhering to predefined eligibility criteria. The timeframe for inclusion spanned from 2010 to 2023, resulting in 218 relevant papers. Chemical structures were visualized using ChemDraw 21.0, PubChem was utilized to search for CID numbers.
RESULTS
Despite being one of the richest biodiverse zones in the world, African natural products are proportionally underreported compared to Asian countries or otherwise. The diterpenes andrographolide (Andrographis paniculata), forskolin (Coleus forskohlii), ent-kauranes from Isodon spp., euphosorophane A (Euphorbia sororia), cafestol & kahweol (Coffea spp.), macrocylic jolkinol D derivatives (Euphorbia piscatoria) and cyathane erinacine A (Hericium erinaceus) illustrated the most encouraging data for further cancer therapy exploration and development.
CONCLUSIONS
Diterpenes from African natural products have the potential to be economically significant active pharmaceutical and medicinal ingredients, specifically focussed on anticancer therapeutics.
Topics: Diterpenes; Biological Products; Humans; Africa; Neoplasms; Antineoplastic Agents, Phytogenic; Animals; Antineoplastic Agents
PubMed: 38718637
DOI: 10.1016/j.phymed.2024.155634