PEA (β/2-phenylethylamine, phenethylamine) is an aromatic amine made up of a benzene ring to which an ethylamine side chain is attached (Figure 1a). The PEA alkaloid group includes important alkaloids. It is a precursor of many natural and synthetic compounds. Several substituted PEAs are pharmacologically active compounds found in plants and animals. This group includes simple phenylamine (tyramine, hordenine) and catecholamine (dopamine). The latter was found in animals and terrestrial plants [10]. The structure of PEA allows substitutions on the aromatic ring, the α and β carbons and terminal amino group. The published papers concern amine compounds in marine algae [11,12], and in the plant kingdom including algae [13].

Sources: Some brown marine algae containing PEA are [11]: Desmerestia aculeata, Desmerestia viridis; Red: Ceramium rubrum, Cystoclonium purpureum, Delesseria sanguine, Dumontia incrassata, Polysiphonia urceolata, Polyides rotundus. Recently the presence of PEA was examined in 17 marine algae and it was found only in six red algae [14]: Gelidium crinale, Gracilaria bursa-pastoris, Halymenia floresii, Phyllophora crispa, Polysiphonia morrowii, Polysiphonia tripinnata. PEA was also found in the microalgae Scenedesmus acutus [15].

Pharmacological activity: PEA in the human brain acts as a neuromodulator and a neurotransmitter. PEA has been shown to relieve depression in 60% of depressed patients. It has been proposed that a PEA deficit may be the cause of a common form of depressive illness [16]. Substituted PEAs are pharmacologically active compounds as hormones, stimulants, hallucinogens, entactogenes, anorectics, bronchodilators and antidepressants [17].

N-acetylphenylethylamine (N-ACPEA, N-(2-phenylethylacetamide; Figure 1b)

Source: N-acetylphenylethylamine was first isolated from the red algae Phyllophora crispa and Gelidium crinale [18].

Pharmacological activity: N-ACPEA induced also rotations ipsilateral to the side of the brain lesion as PEA but its activity was 90% less active than β-PEA [16].

TYR is a monoamine derivative of the amino acid tyrosine.

Source: TYR occurs widely in plants, fungi and animal but is rare in algae. It was detected in the brown alga Laminaria saccharina, and red algae Chondrus crispus and Polysiphonia urceolata [19] and in the microalgae Scenedesmus acutus [14].

Pharmacological activity: TYR is a pharmacologically important compound. It stimulates the central nervous system, causes vasoconstriction, increases heart rate and blood pressure and is also responsible for migraines.

N-Acetyltyramine (N-ACTYR; Figure 1d)

Acetyl derivative of tyramine

Source: It was found in the marine algae Phyllophora crispa and Gelidium crinale [18] and is produced by many microorganisms [14] and terrestrial plants [20].

Pharmacological activity: N-ACTYR is a neuropeptide and an important amine for chemical and pharmacological purposes. The presence of urinary N-ACTYR in neuroblastoma patients was demonstrated [21].

It was first isolated from terrestrial plant Anhanolium fissuratus in 1894 [22] and its structure was elucidated in 1906 [23].

Source: HORD was first obtained from red algae Phyllophora nervosa [new name: Phyllophora crispa] [8a,b], and later from Ahnfeltia paradoxa [24], from Gigartina stellata (Mastocarpus stellatus) [25] and from Gelidium crinale [26]. The amount of HORD was determined in Gelidium crinale [26] and Phyllophora nervosa [27] as 9.54–39.66 μg/g, respectively.

Pharmacological activity: The roles of amine compounds in marine algae are not clear [28]. HORD is diuretic and affects the central nervous system. In the past, HORD was used for the treatment of diarrhea and dysentery [29]. It has a positive inotropic effect upon the heart, increases systolic and diastolic blood pressure, peripheral blood volume and inhibits gut movement [30]. All effects are short and only observable with high doses.

DOP is a catecholamine carrying two hydroxyl groups in the position 3 and 4 of the phenyl ring. It is produced in the organism by decarboxylation of dihydroxyphenylalanine.

Source: DOP was found in animals and several terrestrial plants [9] and only one reference mentions its presence in the green alga Monostroma fuscum [31].

Pharmacological activity: It is a hormone and a neurotransmitter. DOP is a sympathomimetic compound. It was used to treat cardiovascular and kidney disorders [32].

Caulerpin contains two indole groups linked by a cyclic ring containing eight carbons with two carboxy groups. The structure of CLP (I) was first proposed [33,34] and later revised [35]. Its crystal structure [36] was studied. Two CLP (I) analogues CLP (II) and (III) were also isolated from Caulerpa racemosa [37].

Source: CLP (I) was isolated especially from green algae and some from red algae. CLP (I) was first extracted from Caulerpa racemosa, C. sertularioides, C. serrulata [33,34] and later, isolated from various Caulerpa sp. as: C. lamourouxii [38], C. racemosa var. macrophysa, C. racemosa var. laetevirens, C. ashmeadii [39], C. cupressoides, C. paspaloides, C. prolifera, C. sertularioides [40], C. peltata [40–42], C. racemosa var. clavifera [43], C. taxifolia [44,45], C. serrulata [33]. CLP (I) was also isolated from other algae: green; Codium decorticatum [46], Halimeda incrassate [47], and red; Laurencia majuscula (CLP I, II) [48], Hypnea concornis [48], Caloglossa leprieurii [48,49], Chondria armata [50].

The content of CLP (I) in Caulerpa sp. are 15% for C. lentilifera, 5% for C. rasemosa, 2% for C.microphysa and 8% for C. sertulorides [51]. C. taxifolia has bloomed explosively in the Mediterranean Sea and has become a major ecological problem [52].

Pharmacological activity: There are different opinions on the toxicity of CLP (I). Symptoms were observed after the ingestion of Caulerpa genus [33]. It shows low toxicity [43]. C. racemosa extracts showed some cytotoxicity, but CLP (I) isolated from these extracts did not show any activity [53]. CLP (I) exhibited a moderate in-vitro antitumor activity against crown gall tumor [54]. CLP (I) showed moderate antibacterial activity against 8 species of bacteria isolated from algal surface [51]. CLP (I) containing alga Laurencia majuscula showed antifungal activity [55]. CLP (I) has been shown to be a plant growth regulator [55–57]. CLP (I) showed no peroxidase activity [58].

CLS is a bisindole alkaloid with a 7 members central ring and two ≪anti parallel≫ indole cores [59] (Figure 3). It was synthesized by several authors [60–63]. CLS has three isomers: A, B and C [62].

Source: CLS was isolated from Caulerpa serrulata [59].

Several compounds were isolated from Martensia fragilis (M. denticulata) such as: fragilamide, martensines, martefragin A, and denticins.

ALM was isolated from the red alga Haraldiophyllum sp. collected in Dakar (Senegal). ALM is a disubstituted oxazolindole derivate. It has two steroisomers, which correspond to synthesized E and Z isomers [69] (Figure 8).

Laurencia brongniartii is an exceptionally important red algae. The isolated compounds were:

These results showed that halogenated alkaloid types depended on the same algae and collection areas [71].

Many polyhalogenated indoles were identified in Rhodophyllis membranacea collected from the Kaikoura coast (New Zealand). The fractions obtained from the extract of R. membranacea contain polychlorinated and polybrominated alkaloids [75] (Figure 12).

Pharmacological activity: Crude extract of R. membranacea showed strong antifungal activity due to the presences of these polyhalogenated indoles [75].

There are two derivatives: lophocladine A and lophocladine B which were isolated from a red alga Lophocladia sp. collected from Fijian Island (New Zealand) [78] (Figure 15).

Pharmacological activity: The cytotoxic activities of LO A and B were investigated on NCI-H-460 lung cancer and neuro-2a neuroblastoma and MDA-MB-435 breast cancer lines. Only LO B showed moderate cytotoxic activity on MDA-MB-435 and NCI-H-460 cell lines but not on neuro 2-a cell [78].