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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

marine microorganisms --- natural products --- structural elucidation --- biological activities --- structure-activity relationships

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Marine natural products are characterized by high chemical diversity, biochemical specificity, and other molecular properties that make them favorable as lead structures for drug discovery. In this field, one of the main problems is often the reduced natural availability of isolated substances, which can complicate both the structural characterization and possible future developments. For these reasons, the study of bioactive marine metabolites should rely on the development of chemical synthesis and synthetic strategies aimed at the preparation of pure compounds and analogs both for structural confirmation and/or for the large-scale preparation necessary for future applications. Moreover, natural products can be a crucial starting point for the preparation of molecules structurally inspired by the latter, opening the path to new classes of biologically active compounds with pharmacological potential. This book collects original research articles regarding synthetic strategies for secondary marine metabolites and/or analogs that favor applications of these molecules and/or solve structural challenges common in the field of natural substances.

organic synthesis --- meroterpenoids --- thiazinoquinones --- antiproliferative activity --- G0/G1 cell-cycle arrest --- cytostatic --- solid tumor cell lines --- alkylglycerol (AKG) --- ricinoleic acid (RA) --- antimicrobial activity --- structure–activity relationship (SAR) studies --- antibiotics (gentamicin --- tetracycline --- ciprofloxacin and ampicillin) --- marine-inspired --- breast cancer --- bis-indoles --- synthesis --- apoptosis --- carbohydrates --- polysaccharides --- semi-synthesis --- sulfation --- glycosylation --- fucose --- fucosylated chondroitin sulfate --- marine natural product --- largazole --- HDAC inhibitors --- modification --- fluoro olefin --- total synthesis --- natural product --- 7-deazapurine nucleoside --- disaccharide nucleoside --- tubercidin --- aureol --- tetracyclic meroterpenoids --- natural products synthesis --- labdane scaffold --- bioactive diterpenes --- sclareolide --- structure-activity relationships --- TRPV4 channel --- amides/esters --- COVID-19 --- SARS-CoV-2 --- lipophilic iminosugars --- polymer-supported triphenyl phosphine --- cholesterol --- antibacterial iminosugars --- n/a --- structure-activity relationship (SAR) studies

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The interest in opioids such as morphine, the prototypical opioid ligand, has been maintained through the years. The identification of endogenous opioids and their receptors (mu, delta, kappa, and nociceptin), molecular cloning, and the elucidation of the crystal structures of opioid receptors represent key milestones in opioid research. The opioid system modulates numerous pharmacological responses, with therapeutic (i.e., analgesia) and detrimental side effects (i.e., addiction). The medical use and misuse of opioids have dramatically increased, leading to the 21st century opioid crisis. This book presents recent developments in opioid drug discovery, specifically in the medicinal chemistry and pharmacology of new ligands targeting the opioid receptors as effective and safe therapeutics for human diseases. Furthermore, it draws a special attention to advancing concepts and strategies in opioid drug discovery to mitigate opioid liabilities. The diversity among the discussed topics is a testimony to the complexity of the opioid system, which results from the expression, regulation, and functional role of ligands and receptors. The array of multidisciplinary research areas illustrates the rapidly developing basic research and translational activities in opioid drug discovery. This book will serve as a useful reference while also stimulating continued research in the chemistry and pharmacology of opioids and their receptors, with the prospect of developing improved therapies for human diseases, but also improving health and quality of life in general.

opioid receptors --- neurokinin-1 receptor --- peptide synthesis --- receptor binding studies --- functional assay --- writhing test --- tolerance --- Leu-enkephalin --- beta-arrestin --- mu opioid receptor --- delta opioid receptor --- biased signaling --- DADLE --- ischemia --- plasma stability --- morphinan --- BNTX --- δ opioid receptor antagonist --- 1H-NMR experiments --- mechanism elucidation --- peripheral antinociception --- 14-methoxycodeine-6-O-sulfate --- codeine-6-O-sulfate --- opioid peptides and peptidomimetics --- DAMGO --- DALDA --- [Dmt1]DALDA --- KGOP01 --- binding --- molecular docking --- structure-activity relationships --- β2-amino acids --- β2-Homo-amino acids --- µ-opioid receptor --- opioid peptides --- TAPP --- racemic synthesis of β2-amino acids --- peripheral µ-opioid receptors --- analgesia --- peripheral analgesic tolerance --- dysbiosis --- opioid --- bifunctional ligands --- (−)-N-phenethylnorhydromorphone analogs --- [35S]GTPgammaS assay --- forskolin-induced cAMP accumulation assays --- β-arrestin recruitment assays --- MOR and DOR agonists --- respiratory depression --- bias factor --- molecular modeling &amp --- simulation --- δ opioid receptor --- NTI derivative --- sulfonamide --- inverse agonist --- neutral antagonist --- agonist --- opioids --- mu receptor --- opioid side effects --- biased agonism --- partial agonism --- zerumbone --- chronic constriction injury (CCI) --- allodynia --- hyperalgesia --- potassium channels --- over-the-counter drugs --- misuse --- abuse --- opioid drugs --- pharmacology --- codeine --- dihydrocodeine --- loperamide --- opioid peptide --- macrocyclic tetrapeptide --- multifunctional ligands --- kappa opioid receptor --- analgesics --- opioid liabilities --- μ opioid receptor --- receptor model --- biased ligands --- dependence --- pain therapy --- neonatal opioid withdrawal syndrome --- naltrexone --- 6β-naltrexol --- buprenorphine --- G-protein bias --- arrestin recruitment --- respiration --- mitragynine --- heteromer --- internalization --- primary hippocampal culture --- lysosomes --- µ opioid receptor --- molecular dynamics --- docking --- interaction fingerprints --- biased agonists --- SR-17018 --- PZM21 --- morphine --- fentanyl --- diphenethylamines --- design and synthesis --- structure–activity relationships --- partial agonist --- biased agonist --- antagonist --- binding affinity --- selectivity --- n/a

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The present book, a reprint of the Molecules Special Issue "Insecticide, Acaricide, Repellent and Antimicrobial Development", presents key advances in the development of effective and eco-friendly insecticides, acaricides, repellents, and antimicrobials, including products of natural origin.

Lauraceae --- Aedes aegypti --- Aedes albopictus --- Culex quinquefasciatus --- antibacterial --- antifungal --- antioxidants --- compatibility --- date palm dust mites --- host defense --- Oligonychus afrasiaticus --- Metarhizium anisopliae --- natural acaricide --- synergism --- 1-Chlorooctadecane --- Lamiaceae --- Clinopodium nepeta subsp. nepeta --- Clinopodium nepeta subsp. glandulosum --- essential oils --- chemical variability --- biological activities --- Citrullus colocynthis --- spinasterol, 22,23-dihydrospinasterol --- fernenol --- insecticidal activity --- LC50 --- electrical penetration graph --- peach potato aphid --- antifeedants --- attractants --- structure-activity relationships --- fractionation --- reducing activity --- biomolecules --- antibiofilm --- microbial infection --- mangrove --- larvicidal activity --- enzyme inhibition --- Rhizophora mucronata --- repellent --- mosquitoes --- Erigeron --- Conyza bonariensis --- Conyza canadensis --- Conyza sumatrensis --- mosquito --- vector control --- naphthoquinones --- plumbagin --- Spodoptera littoralis --- insect growth inhibition --- carnivorous plants --- Nepenthes --- botanical-based insecticide --- cereals --- green grain protectant --- essential oil nanoformulation --- stored-product beetles --- Tenebrionidae --- Chagas’ disease transmission --- triatomines --- peridomiciliary use --- Argentina --- biopesticides --- bio-based pesticides --- chemical ecology --- pest control --- natural products --- storage --- monoterpenes --- bioinsecticide --- insect pest --- toxicity --- eugenol derivatives --- amino alcohols --- semisynthetic insecticides --- bioinsecticides --- phenylpropanoids --- Spodoptera frugiperda --- urban pests --- agricultural pests --- aphids --- cockroaches --- kissing bugs --- insect vectors --- green insecticides --- moth pests --- non-target toxicity --- stored product pests --- termites --- n/a --- Chagas' disease transmission

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Cancer is one of the major causes of death worldwide. It is a multifactorial heterogeneous disease characterized by the transformation of normal cells into malignant cells, which acquire an uncontrolled growth, immortality, invasiveness, and ability to form distant metastasis. Natural bioactive molecules may interfere with these processes and inhibit the carcinogenesis process. In this book, new molecules and extracts, mainly derived from plants, have been described as being able to alter tumor cell behavior and target several abnormal molecular pathways in cancer cells. Among different cancer cells, the more studied include those derived from glioblastoma, osteosarcoma, lung, breast and gastric cancer. These natural products could be an attractive source for the development of new preventative and therapeutic agents against cancer. They may be more selective and have weaker adverse effects compared to conventional chemotherapy drugs that are actually used for cancer treatment. Clinical trials are necessary to demonstrate whether the in vitro and in vivo animal data are reproduced in humans before the application of natural products in cancer prevention and treatment.

cytotoxic activity --- NCI-60 cancer cell line --- pristimerin --- Salacia crassifolia --- Celastraceae --- Brazilian Cerrado biome --- Salacia elliptica --- Cheiloclinium cognatum --- Plenckia populnea --- Aspergillus fumigatus --- Cordyceps sinensis --- isochromanes --- chiral resolution --- ECD calculation --- cytotoxicity --- coronarin D --- JNK --- osteosarcoma --- Zeylenone --- gastric cancer --- invasion --- migration --- apoptosis --- anti-cancer agents --- anthraquinones --- glycosyltransferase --- Dendrobium officinale --- structure elucidation --- anti-tumor activity --- plantation mode --- AR --- Ganoderma tsugae --- lipogenesis --- prostate cancer --- SREBP-1 --- ursolic acid --- betulinic acid --- triterpenoids --- necrotic --- quercetin --- quercetagetin --- patuletin --- lichen --- secondary metabolites --- tumidulin --- stemness potential --- colorectal cancer cells --- oncogene --- transcriptional regulation --- neferine --- FAK/S6K1 --- autophagy --- human neuroblastoma cells --- natural yellow Monascus pigments --- water-soluble --- antioxidation --- MCF-7 cells --- phloretin --- cell proliferation --- inflammation --- glucose uptake --- Catalpa speciosa --- Taxus cuspidata --- Magnolia acuminata --- phenols --- antioxidants --- anticancer --- Colocasia esculenta --- food bioactive --- tarin --- stable nanocapsules --- entrapment efficiency --- no-toxicity --- preclinical tests --- antitumoral activity --- chemotherapeutic adjuvant --- grape leaves --- ASE --- TP --- Antioxidant activities --- Antiproliferative --- pro-apoptotic effects --- Gene expression --- Nutraceuticals --- Cucurbitacin B --- gefitinib-resistant NSCLC --- EGFR --- lysosomal degradation --- CIP2A --- zerumbone --- cancer --- NF-κB --- IL-6/JAK2/STAT3 --- Akt --- FOXO1 --- multiple myeloma --- quality control --- naringenin --- flavonoids --- traditional preparation --- cancer stem cells --- phytochemicals --- plant-derived foods --- fruit --- vegetable --- cell signaling --- Artemisia absinthium --- endoplasmic reticulum stress --- mitochondrial-dependent pathway --- melanoma --- bee venom --- melittin --- temozolomide --- AKT --- MAPK --- antrodin C --- mTOR --- metabolic stability --- capsazepine --- inflammatory diseases --- ROS --- TRPV1 --- PI3K/AKT/mTOR --- CLE-10 --- LC3 --- MDA-MB-231 --- lactoferrin hydrolysate --- copper --- manganese --- gastric cancer cells --- anti-cancer activity --- molecular mechanism --- natural product alkaloids --- cephalotaxine --- protein synthesis inhibition --- antiproliferation agents --- folk medicine --- DLD-1 cells --- doxorubicin --- chemotherapy --- drug resistance --- CrataBL --- glioblastoma --- mesenchymal stem cells --- microenvironment --- plant lectin --- protease inhibitor --- cryptolepine --- neocryptolepine --- isocryptolepine --- antiproliferative activity --- structure activity relationships --- Licochalcone A --- ATM-Chk2 --- 13-ethylberberine --- mitochondrial ROS --- RT-R breast cancer cells --- diallyl disulfide --- PI3K/Akt/mTOR pathway --- Pulsatilla saponin D --- SB365 --- glioblastoma multiforme --- autophagic flux inhibition --- lysosomal membrane permeabilization --- mitochondrial membrane potential --- CLEFMA --- p38 --- proanthocyanins --- TNF-α --- lung adenocarcinoma --- natural compounds --- cervical cancer --- cell cycle arrest --- dicentrine --- metastasis --- glioma --- semi-synthetic derivative --- ingenol --- Euphorbia tirucalli --- protein kinase C --- seaweed --- porphyran --- carrageenan --- anti-cancer --- natural products --- n/a