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International Journal of Molecular... Oct 2020The so-called "" has become an attractive research area, as an increasing number of natural products containing a sialic acid moiety have been shown to play important... (Review)
Review
The so-called "" has become an attractive research area, as an increasing number of natural products containing a sialic acid moiety have been shown to play important roles in biological, pathological, and immunological processes. The intramolecular lactones of sialic acids are a subclass from this crucial family that could have central functions in the discrimination of physiological and pathological conditions. In this review, we report an in-depth analysis of the synthetic achievements in the preparation of the intramolecular lactones of sialic acids (1,4-, 1,7- and γ-lactones), in their free and/or protected form. In particular, recent advances in the synthesis of the 1,7-lactones have allowed the preparation of key sialic acid derivatives. These compounds could be used as authentic reference standards for their correct determination in biological samples, thus overcoming some of the limitations of the previous analytical procedures.
Topics: Lactones; Sialic Acids
PubMed: 33143039
DOI: 10.3390/ijms21218098 -
International Journal of Molecular... Feb 2021In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are... (Review)
Review
In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF and 1,15-PGF lactones, many 1,15-lactones of E, E, F, F, A, and A were found in the marine mollusc and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed.
Topics: Catalysis; Lactones; Molecular Structure; Prostaglandins; Prostaglandins, Synthetic
PubMed: 33557221
DOI: 10.3390/ijms22041572 -
Molecules (Basel, Switzerland) Mar 2022The sesquiterpene γ-lactone estafiatin , the molecule of which has a structure of 3,4α-epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide, is characteristic of...
The sesquiterpene γ-lactone estafiatin , the molecule of which has a structure of 3,4α-epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide, is characteristic of plants of the genera L. and L. of the family. This article presents the results of chemical modification for three reaction centers of the estafiatin molecule : epoxy cycle, exomethylene group conjugated with γ-lactone carbonyl, and exomethylene group in position C10=C14; and at the same time 33 new derivatives were synthesized, the structures of which were established based on physicochemical constants, spectral data (IR-, PMR-, C-NMR), and X-ray diffraction analysis. The stereo- and regiospecificity, as well as the chemoselectivity of the reaction based on estafiatin molecule , are discussed. The reactivity of the substrate is significantly influenced by the stereochemistry of its molecule, the nature of the reagent, and the reaction medium. Based on the results of in silico screening, derivatives of estafiatin with high binding energies for both DNA-topoisomerase I and DNA-topoisomerase II were identified. The values of the inhibitory dose of IC for estafiatin and its derivatives were determined on cell lines of eight types of tumors. experiments of the samples made it possible to establish that estafiatin and its derivatives have pronounced antitumor activity against Pliss lymphosarcoma, Walker's carcinosarcoma, sarcoma 45, sarcoma-180, alveolar liver cancer PC-1, leukemia P-388 and L-1210, and sarcoma-45 resistant to 5-fluorouracil.
Topics: Asteraceae; Epoxy Resins; Lactones; Magnetic Resonance Spectroscopy
PubMed: 35335225
DOI: 10.3390/molecules27061862 -
Molecules (Basel, Switzerland) Jun 2021A phytochemical investigation of the leaves of the medicinal plant led to the isolation of the two new degraded abietane lactone diterpenoids rubesanolides F () and G...
A phytochemical investigation of the leaves of the medicinal plant led to the isolation of the two new degraded abietane lactone diterpenoids rubesanolides F () and G (). Their structures were elucidated based on the analyses of the HRESIMS and 1D/2D NMR spectral data, and their absolute configurations were determined by ECD spectrum calculations and X-ray single crystal diffraction methods. Compounds and , with a unique γ-lactone subgroup between C-8 and C-20, were found to form a carbonyl carbon at C-13 by removal of the isopropyl group in an abietane diterpene skeleton. Rubesanolide G () is a rare case of abietane that possesses a -fused configuration between rings B and C. The two isolates were evaluated for their biological activities against two cancer cell lines (A549 and HL60), three fungal strains (, and ) and three bacterial strains (, and ).
Topics: A549 Cells; Abietanes; Anti-Infective Agents; Antineoplastic Agents, Phytogenic; Bacteria; Fungi; HL-60 Cells; Humans; Isodon; Lactones; Neoplasms; Plant Leaves
PubMed: 34202760
DOI: 10.3390/molecules26133865 -
Biomedicine & Pharmacotherapy =... May 2020Costunolide (COS) and dehydrocostus lactone (DEH) are two natural sesquiterpene lactones with potential antitcancer activity against a range of cancer cell types both in... (Review)
Review
Costunolide (COS) and dehydrocostus lactone (DEH) are two natural sesquiterpene lactones with potential antitcancer activity against a range of cancer cell types both in vitro and in vivo, particularly for breast cancer and leukemia. There are many researches that have been taken to characterize these pathways and to reveal their anticancer mechanisms of action of COS and DEH. However, while there is a great deal of evidence detailing the effects of COS and DEH on considerable signaling pathways and cellular functions, a global view of their mechanism of action remains elusive. This review systematically summarizes the antitumor activity and mechanism of COS and DEH in the recent reports, and discusses the effect of the key active part (α-methylene-γ-butyrolactone) of COS and DEH against cancer. Moreover, we also discuss the antineoplastic activity of COS and DEH derivatives to improve the cytotoxicity and safety index. We believe this review can provide a systemic reference to develop COS and DEH as anticancer agents.
Topics: Antineoplastic Agents, Phytogenic; Asteraceae; Cell Line, Tumor; Humans; Lactones; Sesquiterpenes
PubMed: 32014691
DOI: 10.1016/j.biopha.2020.109955 -
Molecules (Basel, Switzerland) Feb 2022Sesquiterpene lactones (SL), characterized by their high prevalence in the family, are one of the major groups of secondary metabolites found in plants. Researchers... (Review)
Review
Sesquiterpene lactones (SL), characterized by their high prevalence in the family, are one of the major groups of secondary metabolites found in plants. Researchers from distinct research fields, including pharmacology, medicine, and agriculture, are interested in their biological potential. With new SL discovered in the last years, new biological activities have been tested, different action mechanisms (synergistic and/or antagonistic effects), as well as molecular structure-activity relationships described. The review identifies the main sesquiterpene lactones with interconnections between immune responses and anti-inflammatory actions, within different cellular models as well in in vivo studies. Bioaccessibility and bioavailability, as well as molecular structure-activity relationships are addressed. Additionally, plant metabolic engineering, and the impact of sesquiterpene lactone extraction methodologies are presented, with the perspective of biological activity enhancement. Sesquiterpene lactones derivatives are also addressed. This review summarizes the current knowledge regarding the therapeutic potential of sesquiterpene lactones within immune and inflammatory activities, highlighting trends and opportunities for their pharmaceutical/clinical use.
Topics: Animals; Anti-Inflammatory Agents; Asteraceae; Drug Discovery; Humans; Immunomodulating Agents; Lactones; Sesquiterpenes
PubMed: 35164406
DOI: 10.3390/molecules27031142 -
International Journal of Molecular... Jan 2021Cancer is one of the leading causes of death globally, accounting for an estimated 8 million deaths each year. As a result, there have been urgent unmet medical needs to... (Review)
Review
Cancer is one of the leading causes of death globally, accounting for an estimated 8 million deaths each year. As a result, there have been urgent unmet medical needs to discover novel oncology drugs. Natural and synthetic lactones have a broad spectrum of biological uses including anti-tumor, anti-helminthic, anti-microbial, and anti-inflammatory activities. Particularly, several natural and synthetic lactones have emerged as anti-cancer agents over the past decades. In this review, we address natural and synthetic lactones focusing on their anti-tumor activities and synthetic routes. Moreover, we aim to highlight our journey towards chemical modification and biological evaluation of a resorcylic acid lactone, L-783277 (). We anticipate that utilization of the natural and synthetic lactones as novel scaffolds would benefit the process of oncology drug discovery campaigns based on natural products.
Topics: Antineoplastic Agents, Phytogenic; Biological Products; Cell Line, Tumor; Cell Proliferation; Chemical Phenomena; Chemistry Techniques, Synthetic; Dose-Response Relationship, Drug; Drug Discovery; Humans; Lactones; Molecular Structure; Structure-Activity Relationship
PubMed: 33494352
DOI: 10.3390/ijms22031052 -
Plant Signaling & Behavior Dec 2022Wallr. ( Loefl.) causes severe yield losses of confectionary sunflower in China. While germination of is stimulated by sesquiterpene lactones (STLs) from host...
Wallr. ( Loefl.) causes severe yield losses of confectionary sunflower in China. While germination of is stimulated by sesquiterpene lactones (STLs) from host sunflower ( L.). Dehydrocostus lactone and costunolide isolated from sunflower root exudates are known as STLs to specifically induce germination. Two major confectionary sunflower cultivars, SH363 (highly susceptible to ) and TH33 (resistant to ), were planted in China. However, STLs in these two sunflower cultivars has remained unknown. To identify STLs from root and exudates of sunflower for better understanding the role of stimulants in parasitic interaction of sunflower and , we tested dehydrocostus lactone (DCL) and costunolide (CL) in root and root exudates of susceptible and resistant sunflower cultivars. The stimulant activity of sunflower root exudate and root extract to germination of were also determined. Dehydrocostus lactone and costunolide were identified through ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Both DCL and CL were found in root extracts and root exudates in the whole tested time point from two sunflower cultivars. The concentration of dehydrocostus lactone was higher than that of costunolide at the same tested growth stage of each sunflower cultivar. It was observed that higher quantity of dehydrocostus lactone in susceptible cultivar than resistant cultivar of root and root exudates at later tested developmental stages. However, the amount of CL was no significant difference between SH363 and TH33 at all tested stages. The release amount of DCL from susceptible cultivar is 3.7 folds that of resistant cultivar at 28 DAT. These findings suggested that DCL was the one of the major signal compound in these two sunflower cultivars, and lower dehydrocostus lactone might contribute to the resistance of sunflower TH33 to .
Topics: Chromatography, Liquid; Exudates and Transudates; Germination; Helianthus; Lactones; Orobanche; Plant Extracts; Plant Roots; Sesquiterpenes; Tandem Mass Spectrometry
PubMed: 35060434
DOI: 10.1080/15592324.2022.2025669 -
Journal of Natural Products May 2022Two new lactone lipids, scoriosin () and its methyl ester (), with a rare furylidene ring joined to a tetrahydrofurandione ring, were isolated from , commonly referred...
Two new lactone lipids, scoriosin () and its methyl ester (), with a rare furylidene ring joined to a tetrahydrofurandione ring, were isolated from , commonly referred to as sooty mold. The planar structure of these compounds was assigned by 1D and 2D NMR. The conformational analysis of these molecules was undertaken to evaluate the relative and absolute configuration through GIAO NMR chemical shift analysis and ECD calculation. In addition to the potent antimicrobial activities, compound strongly potentiated the activity of amphotericin B against , suggesting the potential utility of this compound in combination therapies for treating cryptococcal infections.
Topics: Anti-Infective Agents; Antifungal Agents; Ascomycota; Cryptococcus neoformans; Lactones; Lipids; Molecular Structure
PubMed: 35473311
DOI: 10.1021/acs.jnatprod.1c01012 -
FEMS Microbiology Reviews Mar 2013Success in nature depends upon an ability to perceive and adapt to the surrounding environment. Bacteria are not an exception; they recognize and constantly adjust to... (Review)
Review
Success in nature depends upon an ability to perceive and adapt to the surrounding environment. Bacteria are not an exception; they recognize and constantly adjust to changing situations by sensing environmental and self-produced signals, altering gene expression accordingly. Autoinducer-2 (AI-2) is a signal molecule produced by LuxS, an enzyme found in many bacterial species and thus proposed to enable interspecies communication. Two classes of AI-2 receptors and many layers and interactions involved in downstream signalling have been identified so far. Although AI-2 has been implicated in the regulation of numerous niche-specific behaviours across the bacterial kingdom, interpretation of these results is complicated by the dual role of LuxS in signalling and the activated methyl cycle, a crucial central metabolic pathway. In this article, we present a comprehensive review of the discovery and early characterization of AI-2, current developments in signal detection, transduction and regulation, and the major studies investigating the phenotypes regulated by this molecule. The development of novel tools should help to resolve many of the remaining questions in the field; we highlight how these advances might be exploited in AI-2 quorum quenching, treatment of diseases, and the manipulation of beneficial behaviours caused by polyspecies communities.
Topics: Adaptation, Physiological; Bacteria; Bacterial Physiological Phenomena; Gene Expression Regulation, Bacterial; Homoserine; Lactones; Phenotype; Signal Transduction
PubMed: 22712853
DOI: 10.1111/j.1574-6976.2012.00345.x