β-Carboline (9H-pyrido[3,4-b]indole) represents the basic chemical structure for more than one hundred alkaloids and synthetic compounds. The effects of these substances depend on their respective substituent. Natural β-carbolines primarily influence brain functions but can also exhibit antioxidant effects. Synthetically designed β-carboline derivatives have recently been shown to have neuroprotective, cognitive enhancing and anti-cancer properties.
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical synthesis and have played a central role in the development of the field of organic chemistry by providing challenging synthetic targets. The term natural product has also been extended for commercial purposes to refer to cosmetics, dietary supplements, and foods produced from natural sources without added artificial ingredients.
2-Imidazoline (Preferred IUPAC name: 4,5-dihydro-1H-imidazole) is one of three isomers of the nitrogen-containing heterocycle imidazoline, with the formula C3H6N2. The 2-imidazolines are the most common imidazolines commercially, as the ring exists in some natural products and some pharmaceuticals. They also have been examined in the context of organic synthesis, coordination chemistry, and homogeneous catalysis.
Chelerythrine is a benzophenanthridine alkaloid present in the plant Chelidonium majus. It is a potent, selective, and cell-permeable protein kinase C inhibitor in vitro. And an efficacious antagonist of G-protein-coupled CB1 receptors. This molecule also exhibits anticancer qualities and it has served as a base for many potential novel drugs against cancer. Structurally, this molecule has two distinct conformations, one being a positively charged iminium form, and the other being an uncharged form, a pseudo-base.
A depsipeptide is a peptide in which one or more of its amide, -C(O)NHR-, groups are replaced by the corresponding ester, -C(O)OR-. Many depsipeptides have both peptide and ester linkages. Elimination of the N–H group in a peptide structure results in a decrease of H-bonding capability, which is responsible for secondary structure and folding patterns of peptides, thus inducing structural deformation of the helix and β-sheet structures. Because of decreased resonance delocalization in esters relative to amides, depsipeptides have lower rotational barriers for cis-trans isomerization and therefore they have more flexible structures than their native analogs. They are mainly found in marine and microbial natural products.
5-Bromo-DMT (5-bromo-N,N-dimethyltryptamine) is a psychedelic brominated indole alkaloid found in the sponges Smenospongia aurea and Smenospongia echina, as well as in Verongula rigida alongside 5,6-Dibromo-DMT and seven other alkaloids. It is the 5-bromo derivative of DMT, a psychedelic found in many plants and animals.
Cryptophycins are a family of macrolide molecules that are potent cytotoxins and have been studied for potential antiproliferative properties useful in developing chemotherapy. They are members of the depsipeptide family.
Nitroxoline is an antibiotic that has been in use in Europe for about fifty years, and has proven to be very effective at combating biofilm infections. Nitroxoline was shown to cause a decrease in the biofilm density of P. aeruginosa infections, which would allow access to the infection by the immune system in vivo. It was shown that nitroxoline functions by chelating Fe2+ and Zn2+ ions from the biofilm matrix; when Fe2+ and Zn2+ were reintroduced into the system, biofilm formation was reconstituted. The activity of biofilm degradation is comparable to EDTA, but has a history of human use in clinical settings and therefore has a precedent with which to allow its use against “slimy” biofilm infections.
Tropane alkaloids are a class of bicyclic [3.2.1] alkaloids and secondary metabolites that contain a tropane ring in their chemical structure. Tropane alkaloids occur naturally in many members of the plant family Solanaceae. Certain tropane alkaloids such as cocaine and scopolamine are notorious for their psychoactive effects, related usage and cultural associations. Particular tropane alkaloids such as these have pharmacological properties and can act as anticholinergics or stimulants.
Ageliferin is a chemical compound produced by some sponges. It was first isolated from Caribbean and then Okinawan marine sponges in the genus Agelas. It often co-exists with the related compound sceptrin and other similar compounds. It has antibacterial properties and can cause biofilms to dissolve.
Halichondrin B is a polyether macrolide originally isolated from the marine sponge Halichondria okadai by Hirata and Uemura in 1986. In the same report, these authors also reported the exquisite anticancer activity of halichondrin B against murine cancer cells both in culture and in in vivo studies. Halichondrin B was highly prioritized for development as a novel anticancer therapeutic by the United States National Cancer Institute and, in 1991, was the original test case for identification of mechanism of action by NCI's then-brand-new "60-cell line screen" The complete chemical synthesis of halichondrin B was achieved by Yoshito Kishi and colleagues at Harvard University in 1992, an achievement that ultimately enabled the discovery and development of the structurally simplified and pharmaceutically optimized analog eribulin. Eribulin was approved by the U.S. Food and Drug Administration on November 15, 2010, to treat patients with metastatic breast cancer who have received at least two prior chemotherapy regimens for late-stage disease, including both anthracycline- and taxane-based chemotherapies. Eribulin is marketed by Eisai Co. under the tradename Halaven.
Palau'amine is a toxic alkaloid compound synthesized naturally by Stylotella agminata, a species of sea sponge found in the southwest Pacific Ocean. The name of the molecule derives from the island nation of Palau, near which the sponges are found.
Tubulin inhibitors are chemotherapy drugs that interfere directly with the tubulin system, which is in contrast to those chemotherapy drugs acting on DNA. Microtubules play an important role in eukaryotic cells. Alpha- and beta-tubulin, the main components of microtubules, have gained considerable interest because of their function and biophysical properties and has become the subject of intense study. The addition of tubulin ligands can affect microtubule stability and function, including mitosis, cell motion and intracellular organelle transport. Tubulin binding molecules have generated significant interest after the introduction of the taxanes into clinical oncology and the general use of the vinca alkaloids. These compounds inhibit cell mitosis by binding to the protein tubulin in the mitotic spindle and preventing polymerization or depolymerization into the microtubules. This mode of action is also shared with another natural agent called colchicine.
Tectitethya crypta is a species of demosponge belonging to the family Tethyidae. Its classified family is characterized by fourteen different known genera, one of them being Tectitethya. It is a massive, shallow-water sponge found in the Caribbean Sea. This sponge was first discovered by Werner Bergmann in 1945 and later classified by de Laubenfels in 1949. It is located in reef areas situated on softer substrates such as sand or mud. Oftentimes, it is covered in sand and algae. This results in an appearance that is cream colored/ gray colored; however, when the animal is washed free of its sediment coverings, its body plan appears more green and gray. It's characterized with ostia peaking out of its body cavity, with the ability to abruptly open or close, changing its desired water flow rate through its mesohyl.
Stevensine is a bromopyrrole alkaloid originally isolated from an unidentified Micronesian marine sponge, as well as a New Caledonian sponge, Pseudaxinyssa cantharella and Axinella corrugata. Total synthesis of stevensine has been achieved by Ying-zi Xu et al., and investigations into the biosynthetic origin has been explored by Paul Andrade et al. Understanding methods to synthesize stevensine and other similar compounds is an important step to accomplish, as marine sponges contain numerous biologically active metabolites that have been shown to function as anything from antitumor to antibacterial agents when tested for medicinal applications. Reasons for why marine sponges contain so many bio-active chemicals has been attributed to their sessile nature, and the need to produce chemical defenses to ensure survival. However, since many of these compounds naturally occur in small amounts, harvesting the sponges has in the past led to near-extinction of some species.
Dideoxyverticillin A, also known as (+)-11,11′-dideoxyverticillin A, is a complex epipolythiodioxopiperazine initially isolated from the marine fungus Penicillium sp. in 1999. It has also been found in the marine fungus Bionectriaceae, and belongs to a class of naturally occurring 2,5-diketopiperazines.
Fungal isolates have been researched for decades. Because fungi often exist in thin mycelial monolayers, with no protective shell, immune system, and limited mobility, they have developed the ability to synthesize a variety of unusual compounds for survival. Researchers have discovered fungal isolates with anticancer, antimicrobial, immunomodulatory, and other bio-active properties. The first statins, β-Lactam antibiotics, as well as a few important antifungals, were discovered in fungi.
Lacking an immune system, protective shell, or mobility, sponges have developed an ability to synthesize a variety of unusual compounds for survival. C-nucleosides isolated from Caribbean Cryptotethya crypta, were the basis for the synthesis of zidovudine (AZT), aciclovir (Cyclovir), cytarabine (Depocyt), and cytarabine derivative gemcitabine (Gemzar).
Lamellarins are a group of pyrrole alkaloids first isolated in 1985 from the marine mollusk Lamellaria in the waters of Palau. Over 70 lamellarins and similar compounds were subsequently isolated. Other similar compounds include ningalins, lukianols, polycitones, and storniamides.
Pseudoceratina is a genus of sponge within the family Pseudoceratinidae. They are characterized by possession of a dendritic fiber skeleton lacking laminar bark but containing pith. They have been found in a variety of habitats including the Great Barrier reef, the Red Sea, and Jamaica. Sponges of this genus have a microbiome known to produce a variety of chemicals that are used in pharmaceutical and anti-fouling activities. Notably, a species in this genus produces a chemical that is effective in inhibiting the migration of metastatic breast cancer cells.
