Monanchocidins B–E: Polycyclic Guanidine Alkaloids with Potent Antileukemic Activities from the Sponge Monanchora pulchra

Abstract

New unusual polycyclic guanidine alkaloids monanchocidins B-E (2-5) along with monanchocidin A (1), which we recently described, were isolated from the Far-Eastern marine sponge Monanchora pulchra. Their structures were established using spectroscopic data and chemical transformations. Compounds 1-5 show potent cytotoxic activities against HL-60 human leukemia cells with IC50 values of 540, 200, 110, 830, and 650 nM, respectively.

Anticancer agents from marine sponges

“…An interesting fact is that the morpholinone ring unit compound has been found only in the same marine sponge M. pulchra. At the same time, monanchocidin D (20) and monanchocidin E (21) were found with a similar structure of monanchocidin A which was previously described by the same research team [19].…”

“…Sagitol C (17) was investigated for its effects of inhibiting three different tumor cell lines. Sagitol C (17) (19) are special hybrid structures, combined with pentacyclic guanidinium ring systems and the morpholinone ring unit. An interesting fact is that the morpholinone ring unit compound has been found only in the same marine sponge M. pulchra.…”

Structure, synthesis and biological properties of the pentacyclic guanidinium alkaloids

“…in 1989 by Kashman and co-workers. 11 In the following years, several PGA families, namely the crambescidins 12–15 , neofolitispates 16 , fromiamycalin 17 , celeromycalin 17 , monanchocidins 18,19 , monanchomycalins 20,21 and normonanchocidins 22 have been isolated, primarily from marine sponges and other aquatic organisms.…”

Marine Cyclic Guanidine Alkaloids Monanchomycalin B and Urupocidin A Act as Inhibitors of TRPV1, TRPV2 and TRPV3, but not TRPA1 Receptors

“…In recent years it has been shown that the far-eastern marine sponge Monanchora pulchra is also a rich source of novel pentacyclic [3,4,5,6,7], bicyclic [8] and acyclic guanidine alkaloids [9,10]. It is interesting that alkaloids produced in the sponges from different locations and depths had a variety of structures.…”

“…The reasons for these differences are not clear. The alkaloids from the sponge M. pulchra demonstrate a broad spectrum of biological activities, including potent cytotoxic effects [4,5,6], induction of cellular autophagy and lysosomal membrane permeabilization [11], apoptosis [3], as well as inhibition of some cellular receptors [9,10,12,13]. For instance, it was shown earlier that the pentacyclic guanidine alkaloid monanchocidin A demonstrated inhibitory activities in electrophysiology experiments on the mouse muscle and rat α7 nAChRs [13], while acyclic guanidine alkaloids pulchranins A–C inhibited the TRPV1 receptor [9,10,12].…”