Marine-Derived Macrocyclic Alkaloids (MDMAs): Chemical and Biological Diversity

Abstract

The curiosity and attention that researchers have devoted to alkaloids are due to their bioactivities, structural diversity, and intriguing chemistry. Marine-derived macrocyclic alkaloids (MDMAs) are considered to be a potential source of drugs. Trabectedin, a tetrahydroisoquinoline derivative, has been approved for the treatment of metastatic soft tissue sarcoma and ovarian cancers. MDMAs displayed potent activities that enabled them to be used as anticancer, anti-invasion, antimalarial, antiplasmodial, and antimicrobial. This review presents the reported chemical structures, biological activities, and structure–activity relationships of macrocyclic alkaloids from marine organisms that have been published since their discovery until May 2020. This includes 204 compounds that are categorized under eight subclasses: pyrroles, quinolines, bis-quinolizidines, bis-1-oxaquinolizidines, 3-alkylpiperidines, manzamines, 3-alkyl pyridinium salts, and motuporamines.

Exploitation of Marine Molecules to Manage Alzheimer’s Disease

“…Manzamine A ( Figure 2 B) was isolated for the first time from the marine sponge Haliclona sp. in 1986 [ 129 ]. Its activity to inhibit the GSK3beta enzyme noncompetitively was later discovered by in vitro studies when it was observed that an increase in the concentration of ATP did not cause a change in its inhibitory activity.…”

“…About 100 manzamine alkaloids have been isolated from more than 16 species of marine sponges belonging to 10 genera ( Amphimedon, Pachypellina, Haliclona, Reniera, Cribochalina, Petrosia, Ircinia, Hyrtios, Acanthostrongylophora, and Xestospongia ) and belonging to five families (Chalinidae, Niphatidae, Petrosiidae, Thorectidae, Irciniidae). These sponges are found in Okinawa, the Philippines, Indonesia, the Red Sea, Italy, South Africa, and Papua New Guinea [ 128 , 129 ]. AlTarabeen and colleages purified seven manzamines (ircinal E, manzamine A, 8-hydroxymanzamine A, manzamine F, manzamine A N-oxide, 3,4-dihydromanzamine A N-oxide, and nakadomarin A) from Acanthostrongylophora ingens collected at Ambon, Indonesia [ 153 ].…”

Structure–Activity Relationship of Cytotoxic Natural Products from Indonesian Marine Sponges

“…Alkaloids are the most well-known cytotoxic compounds of MNPs isolated from sponges (Althagbi et al 2020 ) and have established their superiority among other classes of compounds (Izzati et al 2021 ). A relatively common moiety found is the β-carboline (a tricyclic 9 H -pyrido[3,4-b]indole ring structure), also known as norharman (Cao et al 2007 ).…”

“…Indonesian marine sponges also provide nitrogenous alkaloid compounds besides the exclusive β-carboline group (Althagbi et al 2020 ). Two of the recent ones are haliclocyclamines C ( 11 ) and cyclostellettamines F ( 12 ), which were isolated from Haliclona sp.…”

Advances in the Global Distribution, Chemical Constituents, and Pharmacology of Hippocampus, a Traditional Marine Chinese Medicine

“…The ocean is rich in biodiversity, and many organisms have evolved unique morphological and physiological characteristics to adapt to challenging environments (Conte et al, 2021). Marine organisms further produce marine natural products (MNPs) with chemical diversity and interesting structures, including peptides, terpenoids, steroids, polyphenols, alkaloids, etc., (Sable et al, 2017;Murray et al, 2018;Wu et al, 2018;Carroll et al, 2019;Althagbi et al, 2020;Ermolenko et al, 2020). Currently, thousands of new MNPs are being reported every year (Carroll et al, 2020(Carroll et al, , 2021.…”