One-pot synthesis and biological evaluation of (2E,4E)-4-arylidene-2-styryl-5-oxopyrrolidine derivatives

Many marine alkaloids possess interesting structures and antitumor activities. Thus, we have synthesized (2 E,4 E)-4-arylidene-2-styryl-5-oxopyrrolidine derivatives of the marine alkaloids, rhopaladins A–D. The cytotoxicities of these derivatives against C-33A, CaSki, SiHa, HeLa, HepG2, and LO2 cells are evaluated by MTT assays. The results show that (2 E,4 E)-2-(4-chlorostyryl)-4-benzylidene- N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide significantly inhibits cancer cell proliferation, with IC50 values against C-33A, CaSki, SiHa, HeLa, and HepG2 cells of 5.56, 9.15, 12.5, 21.4, and 14.5 μM, respectively, and an IC50 value of 86.77 μM against the normal LO2 cell line.

Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2

There have been more than 150 million confirmed cases of SARS-CoV-2 since the beginning of the pandemic in 2019. By June 2021, the mortality from such infections approached 3.9 million people. Despite the availability of a number of vaccines which provide protection against this virus, the evolution of new viral variants, inconsistent availability of the vaccine around the world, and vaccine hesitancy, in some countries, makes it unreasonable to rely on mass vaccination alone to combat this pandemic. Consequently, much effort is directed to identifying potential antiviral treatments. Marine brominated tyrosine alkaloids are recognized to have antiviral potential. We test here the antiviral capacity of fourteen marine brominated tyrosine alkaloids against five different target proteins from SARS-CoV-2, including main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H). These marine alkaloids, particularly the hexabrominated compound, fistularin-3, shows promising docking interactions with predicted binding affinities (S-score = −7.78, −7.65, −6.39, −6.28, −8.84 Kcal/mol) for the main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H), respectively, where it forms better interactions with the protein pockets than the native interaction. It also shows promising molecular dynamics, pharmacokinetics, and toxicity profiles. As such, further exploration of the antiviral properties of fistularin-3 against SARS-CoV-2 is merited.

Synthesis of a new phorbazole and its derivatives

Phorbazoles are chlorinated marine alkaloids isolated from sea sponges and nudibranchs. In this work, a convenience synthetic method leading to a new phorbazole and its derivatives was developed. This synthesis of the novel phorbazole G and its derivatives has been Phorbazoles are chlorinated marine alkaloids containing pyrrole, oxazole, phenol ring units and differ in the number and positions of chlorine atoms. They are isolated from sea sponges and nudibranchs. In this work, a convenient synthetic method leading to a new phorbazole and its derivatives was developed. This synthesis of the synthetic phorbazole G and its derivatives has been achieved in seven steps in good overall yields of 26-52 %. It involved formation of the pyrrole oxazole skeleton followed by chlorination. The pyrrole oxazole skeleton was synthesized from pyrrole and substituted acetophenones, and the key step was cyclodehydration of the amides to give protected oxazoles, followed by hydrolysis. achieved in seven steps in good overall yields of 26.3 - 52.5 %. It involved formation of the pyrrole oxazole skeleton followed by chlorination. The pyrrole oxazole skeleton was synthesized from pyrrole and substituted acetophenones, and the key step was cyclodehydration of the amides to give protected oxazoles, followed by hydrolysis

Marine Alkaloids: Compounds with In Vivo Activity and Chemical Synthesis

Marine alkaloids comprise a class of compounds with several nitrogenated structures that can be explored as potential natural bioactive compounds. The scientific interest in these compounds has been increasing in the last decades, and many studies have been published elucidating their chemical structure and biological effects in vitro. Following this trend, the number of in vivo studies reporting the health-related properties of marine alkaloids has been increasing and providing more information about the effects in complex organisms. Experiments with animals, especially mice and zebrafish, are revealing the potential health benefits against cancer development, cardiovascular diseases, seizures, Alzheimer’s disease, mental health disorders, inflammatory diseases, osteoporosis, cystic fibrosis, oxidative stress, human parasites, and microbial infections in vivo. Although major efforts are still necessary to increase the knowledge, especially about the translation value of the information obtained from in vivo experiments to clinical trials, marine alkaloids are promising candidates for further experiments in drug development.

Magnificines A and B, Antimicrobial Marine Alkaloids Featuring a Tetrahydrooxazolo[3,2-a]azepine-2,5(3H,6H)-dione Backbone from the Red Sea Sponge Negombata magnifica

Investigation of the Red Sea sponge Negombata magnifica gave two novel alkaloids, magnificines A and B (1 and 2) and a new β-ionone derivative, (±)-negombaionone (3), together with the known latrunculin B (4) and 16-epi-latrunculin B (5). The analysis of the NMR and HRESIMS spectra supported the planar structures and the relative configurations of the compounds. The absolute configurations of magnificines A and B were determined by the analysis of the predicted and experimental ECD spectra. Magnificines A and B possess a previously unreported tetrahydrooxazolo[3,2-a]azepine-2,5(3H,6H)-dione backbone and represent the first natural compounds in this class. (±)-Negombaionone is the first β-ionone of a sponge origin. Compounds 1-3 displayed selective activity against Escherichia coli in a disk diffusion assay with inhibition zones up to 22 mm at a concentration of 50 µg/disc and with MIC values down to 8.0 µM. Latrunculin B and 16-epi-latrunculin B inhibited the growth of HeLa cells with IC50 values down to 1.4 µM.

Formal Syntheses of Dictyodendrins B, C, and E by a Multi-substituted Indole Synthesis

The dictyodendrins are a family of marine alkaloids, which possess a highly substituted pyrrolo[2,3-<i>c</i>]carbazole core. This core structure can be regarded as a multi-substituted indole and aniline moiety. To achieve a concise synthesis of dictyodendrins, we planned to capitalize on our previously developed multi-substituted indole synthesis. By using this method along with two C–H functionalizations, formal syntheses of dictyodendrin B, C, and E were achieved.

Formal Syntheses of Dictyodendrins B, C, and E by a Multi-substituted Indole Synthesis

The dictyodendrins are a family of marine alkaloids, which possess a highly substituted pyrrolo[2,3-<i>c</i>]carbazole core. This core structure can be regarded as a multi-substituted indole and aniline moiety. To achieve a concise synthesis of dictyodendrins, we planned to capitalize on our previously developed multi-substituted indole synthesis. By using this method along with two C–H functionalizations, formal syntheses of dictyodendrin B, C, and E were achieved.