There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

This review gives a survey on the latest most representative developments and progress concerning ionic liquids, from their fundamental properties to their applications in catalytic processes. It also highlights their emerging use for biomass treatment and transformation.

Ionic liquids and catalysis: Recent progress from knowledge to applications

The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the br...

Endocannabinoid-Mediated Control of Synaptic Transmission

Historically, natural products have been used since ancient times and in folklore for the treatment of many diseases and illnesses. Classical natural product chemistry methodologies enabled a vast array of bioactive secondary metabolites from terrestrial and marine sources to be discovered. Many of these natural products have gone on to become current drug candidates. This brief review aims to highlight historically significant bioactive marine and terrestrial natural products, their use in folklore and dereplication techniques to rapidly facilitate their discovery. Furthermore a discussion of how natural product chemistry has resulted in the identification of many drug candidates; the application of advanced hyphenated spectroscopic techniques to aid in their discovery, the future of natural product chemistry and finally adopting metabolomic profiling and dereplication approaches for the comprehensive study of natural product extracts will be discussed.

https://minerva-access.unimelb.edu.au/bitstream/handle/11343/265172/PMC3901206.pdf

A historical overview of natural products in drug discovery.

1. Bioactive Metabolites of Marine Algae, Fungi and Bacteria 1. Introduction 2. Secondary Metabolites of Marine Algae 3. Bioactive Metabolites 3.1 Brominated phenols 3.2 Brominated oxygen heterocyclics 3.3 Nitrogen heterocyclics 3.4 Kainic acids 3.5 Guanidine derivatives 3.6 Phenazine derivatives 3.7 Amino acids and amines 3.8 Sterols 3.9 Sulfated polysaccharides 4. Marine Bacteria and Fungi 5. Micro Algae 6. Concluding Remarks References 2. Bioactive Metabolites of Marine Invertebrates 1. Introduction 2. Bioactive Metabolites 2.1 Steroids 2.2 Terpenoids 2.3 Isoprenoids 2.4 Prostaglandins 2.5 Quinones 2.6 Brominated compounds 3. Marine Toxins 3.1 Tetrodotoxin 3.2 Saxitoxin 3.3 Pahutoxin 4. Marine Nucleosides 4.1 Nitrogen-sulphur heterocyclics 5. Bioactive Metabolites of Marine Sponges 6. Marine Invertebrates of the Andaman and Nicobar Islands 6.1 Coelenterates 6.2 Sea Anemones 6.3 Corals 6.4 Bryozoans 6.5 Molluscs 6.6 Echinoderms 6.7 Sea-urchins 6.8 Tunicates 7. Concluding Remarks References 3. Separation and Isolation Techniques 1. Introduction 2. Separation Techniques 2.1 Water soluble constituents 2.2 Ion-exchange chromatography 2.3 Reverse-phase (RP) columns 2.4 High/medium pressure chromatography 2.5 Combination of ion-exchange and size-exclusion chromatography 3. Bioassay Directed Fractionation 4. General Fractionation 5. Isolation Procedures 5.1 Amino acids and simple peptides 5.2 Peptides 5.3 Nucleosides 5.4 Cytokinins 5.5 Alkaloids 6. Marine Toxins 6.1 Saxitoxin 6.2 Brevetoxins 6.3 Tetrodotoxin 6.4 Ciguatoxin and its congeners 6.5 Maitotoxin 6.6 Palytoxin and its congeners 6.7 Gambierol 6.8 Okadaic acids and its congeners 6.9 Miscellaneous toxins 7. Concluding Remarks 4. Biological, Toxicological and Clinical Evaluation 1. Introduction 2. Types of Screening 2.1 Individual activity screening 2.2 Broad biological screening 3. Screening Models and Activity 3.1 Antibacterial and antifungal activities 3.2 Antileishmanial activity 3.3 Anthelmintic activity 3.4 Antimalarial activity 3.5 Antiviral activity 3.6 Antiinflammatory activity 3.7 Analgesic activity 3.8 Antiallergic activity 3.9 Antiarrhythmic and antithrombotic activities 3.10 Hypolipidaemic activity 3.11 Hypoglycaemic activity 3.12 Hypotensive activity 3.13 Antihypertensive activity 3.14 Diuretic activity 3.15 Adaptogenic and immunomodulatory activities 3.16 Immunomodulation activity 3.17 Hepatoprotective activity 3.18 Choleretic and anticholestatic activities 3.19 Acute toxicity and CNS activities 3.20 Isolated tissues 4. Anticancer Screening 4.1 Selection of materials 4.2 In vitro and in vivo activity 4.3 Screening methods 4.4 Screening problems 4.5 Current approach and status 5. Testing Methods 6. Toxicity Evaluation 6.1 Regulatory toxicity 6.2 Reproductive studies 6.3 Teratological study 6.4 Pre- and postnatal study 6.5 Carcinogenic study 6.6 Mutagenic study 7. Use of Animals in Experiments 8. Clinical Trials 8.1 Clinical trials prot

/pdf/bioactive-marine-natural-products-56ivkjgxsn.pdf

Bioactive Marine Natural Products

A role for caveolae/lipid rafts in the uptake and recycling of the endogenous cannabinoid anandamide.

A class of hybrid molecules consisting of 4-aminoquinoline and pyrimidine were synthesized and tested for antimalarial activity against both chloroquine (CQ)-sensitive (D6) and chloroquine (CQ)-resistant (W2) strains of Plasmodium falciparum through an in vitro assay Eleven hybrids showed better antimalarial activity against both CQ-sensitive and CQ-resistant strains of P falciparum in comparison to standard drug CQ Four molecules were more potent (7–8-fold) than CQ in D6 strain, and eight molecules were found to be 5–25-fold more active against resistant strain (W2) Several compounds did not show any cytotoxicity up to a high concentration (60 μM), others exhibited mild toxicities, but the selective index for the antimalarial activity was very high for most of these hybrids Two compounds selected for in vivo evaluation have shown excellent activity (po) in a mouse model of Plasmodium berghei without any apparent toxicity The X-ray crystal structure of one of the compounds was also determined

/pdf/novel-4-aminoquinoline-pyrimidine-based-hybrids-with-krbr66e3er.pdf

Novel 4-aminoquinoline-pyrimidine based hybrids with improved in vitro and in vivo antimalarial activity.

The chemical, biological and ecological diversity of the marine ecosystem has contributed immensely in the discovery of extremely potent compounds that have shown potent activities in antitumor, analgesia, antiinflammatory, immunomodulation, allergy, anti-viral etc. The compounds of marine origin are diverse in structural class from simple linear peptides to complex macrocyclic polyethers. The recent advances in the sophisticated instruments for the isolation and characterization of marine natural products and development of high-throughput screening, have substantially increased the rate of discovery of various compounds of biomedical application. Didemnin was the first marine peptide that entered in human clinical trials in US for the treatment of cancer and other compounds such as dolastatin-10, soblidotin, didemnin B, ecteinascidin 743, girolline, aplidine, cryptophycins (also arenastatin A), bryostatin 1, ILX 651, kahalalide F, E7389, discodermolide, ES-285 (spisulosine), HTI-286 (hemiasterlin derivative), squalamine, KRN-7000, vitilevuamide, Laulimalide, Curacin A, diazonamide, peloruside A, eleutherobin, sarcodictyin, thiocoraline, salicylihalimides A, ascididemnin, CGX-1160, CGX-1007dictyodendrins, GTS-21 (aka DMBX), manoalide, IPL-576,092 (aka HMR-4011A) have entered in the clinical trials. This article summarize clinical status and synthetic advances of some of these compounds.

Clinical status of anti-cancer agents derived from marine sources

The increasing drug resistance of Mycobacterium tuberculosis to the currently used drugs and HIV coinfection has caused alarm in the international scientific community. Subsequently, there is an urgent need for the development of new drug molecules with newer targets and with an alternative mechanism of action. Since the last 50 years, the same long-duration, multidrug treatment plan is being followed for the treatment of tuberculosis. The objective of this review article is to critically analyze the antitubercular potential of various classes of compounds (quinoline, diamine, quinolone, fluoroquinolone, quinone, nitroimidazole, terpenoid, isonicotinyl, oxazolidinone, pyrimidine, and purine), their possibility to be a future drug candidate, and latest information on the clinical status of some novel antitubercular compounds. Compounds such as moxifloxacin, PA824, and TMC207 are well tolerated and there is no adverse effect shown by them. Moxifloxacin and gatifloxacin shows cross-resistance to the currently used drugs while no cross-resistance observed in case of TMC207 and PA824. Some compounds like OPC67683 and PA824 are bactericidal in nature.

Diwan S. Rawat

Papers

Bioactive Marine Natural Products

A role for caveolae/lipid rafts in the uptake and recycling of the endogenous cannabinoid anandamide.

Novel 4-aminoquinoline-pyrimidine based hybrids with improved in vitro and in vivo antimalarial activity.

Clinical status of anti-cancer agents derived from marine sources

Antituberculosis drug research: a critical overview.