Structure, synthesis and biological properties of the pentacyclic guanidinium alkaloids

Abstract

The pentacyclic guanidinium alkaloids (PGAs) are a family of marine natural products that possess a poly-cyclic guanidine-containing core and a long alkyl chain tethered spermidine-derived tail that is rarely observed in other natural products. These natural products exhibit potent activities on a wide range of organisms and therefore have attracted the attention of many synthetic chemists; however, the structure-activity relationships and mechanisms of action of PGAs remain largely elusive. Herein we summarize the structure, synthesis, toxicity and mechanisms of action of PGAs and highlight their potential as chemical probes and/or therapeutic leads.

Monanchocidin A From Subarctic Sponges of the Genus Monanchora and Their Promising Selectivity Against Melanoma in vitro

“…Ptilomycalin A like compounds are known to activate the ERK1/2 and JNK1/2, ensuing AP-1 activation and resulting in p53-independent programmed cell-death and the arrest of S-phase cell cycle (Dyshlovoy et al, 2016). While there are several hypotheses for the mechanism of action (MOA) of this class of molecules, the function at a molecular level remains largely unresolved (Shi et al, 2017). This data shows the potential of monanchocidin A in anticancer activity and hence, further studies should be done to modulate the activity and to further explore the mechanism of action in these kinds of cancer cells.…”

Recent Advances in the Isolation, Synthesis and Biological Activity of Marine Guanidine Alkaloids

“…Among these, Monanchora was the most popular genus to have been chemically investigated, with diverse and complex cyclic or linear MGAs being isolated and determined. Accordingly, this section will be described based on the MGAs from different sponge genera [ 7 , 11 ].…”

“…In recent years, the impressive diversity and complexity of cyclic and/or linear guanidine MNPs were observed as PKS (polyketide synthase) and/or NRPS (nonribosomal peptide synthetase) derivatives, terpene and/or peptide conjugates, etc. [ 7 , 11 ]. These metabolites were mainly derived from various beautiful marine sponges, mollusks, and ascidians in different locations.…”

The Oxepane Motif in Marine Drugs

“…Concerning the synthesis of the members in this family, fantastic efforts towards the development of chemical tools to prepare these intriguing structures have been addressed [ 121 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ]. Since there are several in-depth works regarding the total synthesis of many compounds (or their fragments) in the family [ 141 , 142 , 143 , 144 , 145 ], addressing all of them would be out of the scope of this review.…”