Antimicrobial Activity of Securamines From the Bryozoan Securiflustra securifrons

Abstract

Natural products and their derivatives have served as powerful therapeutics against pathogenic microorganisms and are the mainstay of our currently available treatment options to combat infections. As part of our ongoing search for antimicrobial natural products from marine organisms, one fraction prepared from the Arctic marine bryozoan Securiflustra securifrons was found to be active against the human pathogenic bacterium Streptococcus agalactiae (gr. B). Chemical investigation of the fraction revealed that it contained several variants of the highly modified secondary metabolites known as securamines. The securamines are alkaloids sharing a common isoprene-histamine-tryptamine backbone. In this study, we describe the antimicrobial activities of securamine C, E, and H – J (4, 5, and 1-3) and the attempt to deconvolute the mode of action of 1.

Marine Pharmacology in 2019‐2021: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti‐Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…As shown in Table 1, and Figure 1, in 2019-2021, 13 antiprotozoal (antimalarial, antileishmanial and antitrypanosomal) and antituberculosis studies with structurally characterized marine natural products (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43), isolated from bacteria, sponges, ascidians, zoanthids, hydroids, fish and algae reported novel pharmacological mechanisms of action targeting Plasmodium falciparum (P. falciparum) lysyl-tRNA synthetase, P. falciparum proteins actin and sortilin, P. falciparum liver-stage parasite, P. falciparum transition ring to early trophozoite transition, amoebae Acanthamoeba castellani programmed cell death induction mechanisms, Trichomonas vaginalis membrane disruption, Trypanosoma cruzi trypomastigote and amastigotes plasma membrane integrity, Trypanosoma cruzi cysteine protease cruzain, and Schistosoma mansoni parasite egg-production.…”

“…Chakraborty and colleagues similarly discovered a macrocyclic polyketide (20), isolated from the marine red macroalga Hypnea valentia-associated heterotropic bacterium Shewanella algae, with siderophore mode of action which correlated with docking "with the binding site of PBP2a" [32]. Hansen and colleagues characterized the alkaloid securamine H (21), purified from the Arctic marine bryozoan Securiflustra securifrons, which potently inhibited Staphylococcus aureus by a reduction of metabolic activity that did not appear to involve cell membrane disruption nor "interfere(nce) with DNA replication, transcription or translation" [33]. Hansen and colleagues reported the isolation and characterization of a cysteine-rich peptide turgencin A (22) from the Arctic marine colonial ascidian Synoicum turgens, which displayed potent Gram-negative and Gram-positive antimicrobial activity via a dose-and time-dependent mechanism that caused immediate loss of " membrane integrity" resulting in a "rapid effect on cell viability" [34].…”

Marine natural products

“…602 The antimicrobial activity of several of the brominated indole alkaloids securamines has been assessed and they were shown to be selective inhibitors of Gram-positive strains with securamines E and I displaying weak inhibition of two and three strains respectively, whilst securamine H exhibited moderate inhibition of four strains. 603 A review of the four total syntheses of hinckdentine A has been published 604 and a new application of diffusion ordered NMR spectroscopy (DOSY) for molecular weight determination of NPs used the recently discovered alkaloids convolutamines K and L in comparsion to volutamine F to illustrate the utility of the methodology. 605…”

An oxidative photocyclization approach to the synthesis of Securiflustra securifrons alkaloids

“…We envisioned that N 5 -benzyloxymethyl (BOM) securamine A ( 14) might serve as a common precursor to the three distinct isolates shown in Fig. 1A and that 14 could be derived from the isomeric a,b-unsaturated g-lactam 15 through a cycloisomerization (34,35).…”

“…1A) (2). Subsequently, the cytotoxic hexacyclic bis(aminal) isolates securamines D (3) and C (4) and related isolates that differ in the oxidation state at the C2-C3 linkage [such as securamine G (5)] or the halogenation pattern on the indoline [such as securamine I (6)] were discovered (3)(4)(5). Despite their relatively small structures, these alkaloids present major challenges to chemical synthesis, including an unstable cis-enamide, a neopentylic secondary alkyl chloride, a basic haloimidazole, and a labile halogenated indoline residue.…”