Chemical cues from sessile hosts can attract mobile and associated organisms and they are also impotant to maintain associations and overall biodiversity, but the identity and molecular structures of these chemicals have been little explored in the marine environment. Secondary metabolites are recognized as possible chemical mediators in the association between species of Laurencia and Aplysia, but the identity of the compounds has not been established. Here, for the first time, we experimentally verify that the sesquiterpene (+)-elatol, a compound produced by the red seaweed Laurencia dendroidea, is a chemical cue attracting the associated sea hare Aplysia brasiliana. In addition to revealing the nature of the chemical mediation between these two species, we provide evidence of a chemical cue that allows young individuals of A. brasiliana to live in association with L. dendroidea. This study highlights the importance of chemical cues in Laurencia-Aplysia association.
Leishmaniasis and Chagas disease are neglected tropical diseases that cause problems in developing countries. The causative agents, Leishmania spp. and Trypanosoma cruzi, produce a clinical picture that can be fatal for the patient, such as Chagas heart disease, visceral leishmaniasis and megacolon, among others. Current treatments for these diseases are not very effective and highly toxic, since they require very prolonged treatments. The development of innovative, effective and safe drugs to fight infections caused by these parasites remains a challenge. For this reason, in recent years, there has been an increase in the search for new therapies. In this study, the antikinetoplastid activity of 13 sesquiterpene lactones obtained from Palythoa aff. clavata was screened against L. amazonensis, L. donovani and T. cruzi. The results revealed that the sesquiterpene lactones anhydroartemorin (2), cis,trans-costunolide-14-acetate (3) and 4-hydroxyarbusculin A (11) were the most selective against the kinetoplastid species studied. These molecules seem to induce the mechanisms involved in an apoptotic-like death or programmed cell death (PCD) in the kinetoplastids, and since they do not cause necrosis, the inflammatory events associated with this type of cell death will not be triggered.
Naegleria fowleri is an opportunistic protozoon that can be found in warm water bodies. It is the causative agent of the primary amoebic meningoencephalitis. Focused on our interest to develop promising lead structures for the development of antiparasitic agents, this study was aimed at identifying new anti-Naegleria marine natural products from a collection of chamigrane-type sesquiterpenes with structural variety in the levels of saturation, halogenation and oxygenation isolated from Laurencia dendroidea. (+)-Elatol (1) was the most active compound against Naegleria fowleri trophozoites with IC50 values of 1.08 μM against the ATCC 30808™ strain and 1.14 μM against the ATCC 30215™ strain. Furthermore, the activity of (+)-elatol (1) against the resistant stage of N. fowleri was also assessed, showing great cysticidal properties with a very similar IC50 value (1.14 µM) to the one obtained for the trophozoite stage. Moreover, at low concentrations (+)-elatol (1) showed no toxic effect towards murine macrophages and could induce the appearance of different cellular events related to the programmed cell death, such as an increase of the plasma membrane permeability, reactive oxygen species overproduction, mitochondrial malfunction or chromatin condensation. Its enantiomer (−)-elatol (2) was shown to be 34-fold less potent with an IC50 of 36.77 μM and 38.03 μM. An analysis of the structure–activity relationship suggests that dehalogenation leads to a significant decrease of activity. The lipophilic character of these compounds is an essential property to cross the blood-brain barrier, therefore they represent interesting chemical scaffolds to develop new drugs.
The concept of “Smart Secondary Metabolites” is introduced here to describe a privileged class of natural products defined by structural originality, biosynthetic adaptability, and broad interaction potential with biological systems. Elatol, a halogenated sesquiterpene chiefly produced by Laurencia red seaweeds and occasionally accumulated by their consumers, exemplifies this concept with remarkable clarity. Its biosynthesis unfolds from farnesyl diphosphate via γ-bisabolane cations, bromochlorination, and stereoselective cyclization to chamigrene scaffolds, generating both (+)- and (–)-enantiomers, two metabolites with clearly distinct potential ecological roles and pharmacological profiles. This review synthesizes the current state of knowledge on elatol’s distribution, biosynthetic origins, ecological relevance, and therapeutic potential. Elatol serves as a multifunctional chemical mediator, fulfilling defensive, communicative, and regulatory roles whose intensity shifts in response to herbivory, biofouling, temperature, and salinity. In parallel, its potent activities against infectious, metabolic, and neoplastic diseases highlight its growing value as a drug lead, reflected in a rising number of patent claims. Altogether, elatol emerges as a model Smart Secondary Metabolite whose ecological sophistication and biochemical versatility position it as a promising scaffold for marine-derived drug discovery.
In recent years, the pufferfish Lagocephalus lagocephalus has been recorded with unusual frequency in coastal areas of the Canary Islands. The most notable episodes occurred in March and November 2017, when numerous shoals were observed along the coasts of the Western Canary Islands. A toxicological study of these episodes was carried out, analyzing liver, kidney, gonads, skin, and muscle of a representative population. In all toxic samples (33.3% and 41.7% of specimens in March and November 2017, respectively), only the liver extract showed toxicities, using a mouse biological assay (MBA). The toxicological profile was determined by UHPLC-MS-MS, identifying saxitoxin (STX) and tetrodotoxin (TTX) congeners. This analytical methodology was optimized to determine 26 marine toxins. Thus, in the March 2017 episode, the toxicological profile was characterized by the co-occurrence of tetrodotoxins (TTX and 4-epiTTX) and paralytic shellfish toxin (PST) analogues (dcSTX, dcneoSTX, and doSTX); however, STX and neoSTX emerged as the dominant toxins in specimens collected during the November 2017 episode. The results show that L. lagocephalus in the Canary Islands presents a variable and dynamic toxicological profile, strongly influenced by environmental factors. These findings highlight the need for continued monitoring and for analytical approaches capable of capturing this complexity and assessing potential risks to public health.