Table 1 General summary of the articles on marine natural products and their in vitro activity included in this review
Parasite form (IC50 or EC50) | Cytotoxicity | Compounds | Classes | Sources | Organisms | Country | Refs |
|---|---|---|---|---|---|---|---|
Marine-derived alkaloids | |||||||
Leishmania major (0.75 µmol/L) and L. donovani (7.02 µmol/L) promastigotes; Plasmodium falciparum 3D7 late trophozoites and schizonts (9.08 µmol/L); Trypanosoma brucei brucei intracellular amastigotes (0.78 µmol/L) | NT | Paenidigyamycin A (1) (Fig. 2a) | Alkaloid | Mangrove rhizosphere soil bacterium | Paenibacillus polymyxa strain De2sh | Ghana | [22] |
L. donovani (115.41 µmol/L) promastigotes; T. brucei brucei intracellular amastigotes (28.75 µmol/L) | Mouse macrophages RAW 264.7 cells (selectivity index 8.70) | Paenidigyamycin G (2) | [23] | ||||
L. infantum, L. amazonensis (promastigotes), and T. cruzi epimastigotes (NA) | HepG2 (16 ± 1 μmol/L) | Pseudoceratidine (1) and its derivatives (2–12) (Fig. 2b) | Alkaloid | Marine sponge | Tedania braziliensis | Brazil | [24] |
P. falciparum 3D7 and K1 strains trophozoites and schizonts (0.96–1.24, 5.11–6.49, and 3–6 μmol/L) | Pseudoceratidine (1), 4 + 5, and 9 + 10 (inseparable structural isomers) | ||||||
T. brucei brucei trypanosomes (15.26 and 7.48 μmol/L) | J774.1 macrophages (IC50 > 200 μmol/L) | Hyrtiodoline A (1) and known compounds (2–5) (Fig. 2c) | Alkaloid | Coasts of the Red Sea sponge | Hyrtios sp. | Egypt | [25] |
P. falciparum (K1 and FCR3) late trophozoites and schizonts (1.03 and 0.77 μg/ml) | MRC-5 (15.99 μg/ml) | Ceratinadin E (1) | Alkaloid (Fig. 2d) | Marine sponge | Pseudoceratina sp. | Japan | [26] |
NA | MRC-5 (> 50 μg/ml) | Ceratinadin F (2) | |||||
P. falciparum (K1 and FCR3) (3.77 and 2.45 μg/ml) | MRC-5 (12.65 μg/ml) | Psammaplysin F (3) | |||||
P. falciparum 3D7 late trophozoites and schizonts (12–21 μmol/L) | HEK293 at 40 μmol/L (17–37%) | Orthoscuticellines A and B (1 and 2), orthoscuticellines C−E(3−5), and six known compounds (6−11) (Fig. 2e) | Alkaloid | Bryozoa from storm debris from Korora beach | Orthoscuticella ventricosa | Australia | [27] |
L. amazonensis promastigotes and amastigote (0.06–10.65 μmol/L), L. donovani promastigotes (0.50– > 40 μmol/L) and T. cruzi epimastigote (2.86–14.56 μmol/L) | J774A.1 (8.74 ± 0.72, 5.20 ± 1.75; > 40, > 40 μmol/L) | Indolocarbazole staurosporine (STS, 1–4) (Fig. 2f) | Alkaloids | Sediment bacterium | Streptomyces sanyensis | Ecuador | [28] |
Marine-derived terpenes and terpenoids | |||||||
L. donovani amastigotes (18.8 µg/ml), T. brucei rhodesiense trypomastigotes (11.8 µg/ml), T. cruzi trypomastigotes (47.8 µg/ml); and drug-resistant P. falciparum K1 late trophozoites and schizonts (0.65 µg/ml) | RSM L6 (56.6 μg/ml) | Bifurcatriol (1) (Fig. 3a) | Diterpene | Shore of Kilkee brown alga | Bifurcaria bifurcate | Ireland | [29] |
L. donovani amastigotes (NA) | A549 (> 50 μmol/L) | Keikipukalides (1), | Diterpene (Fig. 3b) | Antarctic deep-sea octocoral—Cnidaria | Plumarella delicatissima | Falkland Islands (Islas Malvinas) | [30] |
L. donovani amastigotes (1.9–12 μmol/L) | Keikipukalides (2–5), pukalide aldehyde (6), and norditerpenoid ineleganolide (7) | ||||||
L. amazonensis promastigotes (15.47 ± 0.26 and 36.81 ± 5.20 μmol/L) and T. cruzi epimastigotes ( 5.62 ± 2.48 and 35.29 ± 4.09 μmol/L) | J774.A1 (23.4 ± 5.62 μmol/L and 69.98 ± 0.14 μmol/L) | Spiralyde A (1) and 3,4-epoxy-7,18-dolabelladiene (2) (Fig. 3c) | Diterpene | Off the coast (1.5 m) brown alga | Dictyota spiralis | Tunisia | [31] |
L. amazonensis and T. cruzi (> 100.00 μmol/L) | NT | Compounds 3–6 | |||||
P. falciparum strain Dd2 trophozoites (3.51, 2.11 and 0.8 µmol/L) | NT | Smenotronic acid (1), ilimaquinone (2), and pelorol (3) (Fig. 3d) | Sesquiterpenoids | Near shore sponge | Hyrtios erectus | Chuuk Island, Federated States of Micronesia | [32] |
L. infantum promastigotes and amastigotes (44.9 ± 4.3 and 94.4 ± 10.1 µmol/L) | Murine macrophages (126.6 ± 21.1 and 84.5 ± 12.5 μmol/L) | (3R)- and 1(3S)-tetraprenyltoluquinol (1a/1b) and (3R)- and (3S)-tetraprenyl Toluquinone (2a/2b) (Fig. 3e) | Terpenoids | Marine macroalgae | Cystoseira baccata | Portugal | [33] |
L. amazonensis intracellular amastigotes (20.2 and 22.9 μmol/L) | Mouse peritoneal macrophages (300 and 200 μmol/L) | Atomaric acid and its methyl ester derivative (Fig. 3f) | Diterpene | Brown alga snorkeling at a depth of 2–3 m | Stypopodium zonale | Brazil | [34] |
T. cruzi intracellular amastigote 5.4 µmol/L) | Vero cells (21.0 ± 0.9 μg/ml) | 5-chloro-1-(E)-chlorovinyl-2,4-dibromo-1,5-dimethylcyclohexane (1) | Terpenes (Fig. 3g) | Snorkeling at a depth of 2–5 m red and brown algae | Plocamium brasiliense | Brazil | [9] |
T. cruzi (2 µmol/L) | Vero cells (40.2 ± 4.9 μg/ml) | Halogenated monoterpenes (F), and atomaric acid meroditerpene (2) | Stypopodium zonale | ||||
Promastigotes of L. amazonensis, L. donovani and epimastigote of T. cruzi (5.40–46.45 μmol/L) | J774A.1 (> 100 µmol/L) | Oxasqualenoid metabolites (1–11) (Fig. 3h) | Polyether triterpenoids | Marine red alga | Laurencia viridis | Spain | [35] |
T. cruzi trypomastigote (32 μmol/L) and intracellular amastigotes (40 μmol/L) | BMM (> 200 μmol/L) | Isololiolide (Fig. 3i) | Carotenoid | Cnidarian got at depth of 1 to 14 m | Macrorhynchia philippina | Brazil | [36] |
P. falciparum 3D7 (80 µmol/L) | Jurkat, MDA-MB-231, U2OS, and A549 cell lines (24.9, 32.3, 41.7 and > 100 μmol/L) | Sinuketal (1), | Terpenoids (Fig. 3j) | South China Sea soft corals | Sinularia sp. | Yongxing Island, China | [37] |
P. falciparum 3D7 (NT) | HeLa, HCT-116 and 11.6, 33.3 and > 100 μmol/L) | Sinulins A and B (2 and 3), sinulins C and D (4 and 5), sesquiterpenoids (6–13) and cembranoids (14–21) | |||||
Marine-derived amino acids, peptide, amides, and polyketide | |||||||
T. brucei brucei trypanosomes (47 nmol/L) | MRC-5 cells (> 10 μmol/L) | Janadolide (Fig. 4a) | Cyclic polyketide-peptide | Marine coast cyanobacterium | Okeania sp. | Japan | [38] |
P. falciparium late trophozoites and schizonts (0.14 μmol/L) | MRC-5 cells (> 10 μmol/L) | Ikoamide (Fig. 4b) | Lipopeptide | Okeania sp. | Japan | [39] | |
P. falciparum late trophozoites and schizonts (0.52 and 1.0 μmol/L) | HeLa cells (10 μmol/L) | Hoshinoamides A (1) and B (2) (Fig. 4c) | Lipopeptides | Caldora penicillata | Japan | [40] | |
T. brucei brucei GUT trypanosomes (IC50 = 6.1 nmol/L) | MRC-5 cells (IC50 > 25 μmol/L) | Hoshinolactam (1) (Fig. 4d) | Lactam | Oscillatoria sp. | Japan | [41] | |
P. falciparum 3D7 and Dd2 ring stage (777.9–598.5 nmol/L) | HEK-293 cells (Only comp. 2–cytotoxic) | Herbimycin G (1) and elaiophylin (2), Cyclo-l-Pro-l-Leu (3), Cyclo-l-Pro-l-Phe (4), Cyclo-l-Pro-l-Val (5), Cyclo-l-Pro-l-Tyr (6) (Fig. 4e) | Polyketides | Bacterium from ascidian Symplegma rubra | Streptomyces sp. (USC-16018) | Australia | [42] |
P. falciparum blood-stages (0.99 and 1.5 µmol/L) | HEK293T (> 4.8 and 19 μmol/L), HepG2 (NT and > 23 μmol/L) | Ulongamide A (2), lyngbyabellin A (3), | Peptide | Reef slopes offshore cyanobacterium | Moorea producens | Island in Fiji | [43] |
Liver-stage P. berghei liver schizonts (EC50 = 11, 7.1, and 4.5 µmol/L) | HEK293T (> 23, > 31, and > 13 μmol/L), HepG2 (> 23, 17, and > 13 μmol/L) | Kakeromamide B (1), 18E-lyngbyaloside C (4), and lyngbyaloside (5) (Fig. 4f) | |||||
Marine-derived quinones, macrolide, lactones, and sterol | |||||||
T. brucei strain TC221 trypanosomes (3.38 (48 h) and 5.26 μmol/L (72 h) | Macrophages (J774.1) (> 200 μmol/L) | Fridamycin H (1) | Anthraquinones (Fig. 5a) | Bacterium from red Sea sponge | Actinokineospora spheciospongiae sp. nov | Egypt | [44] |
NA | Fridamycin I (2), actinosporin C (3), D (4), and G (5) | ||||||
P. falciparum Dd2 in blood-stage (223 nmol/L) and intracellular L. donovani (4.67 μmol/L) | HepG2 (extract not cytotoxic 25 μg/ml) | Palstimolide A (Fig. 5b) | Macrolide | Central Pacific Ocean cyanobacterium | Leptolyngbya sp. | USA | [45] |
P. falciparum strain HB3 (NA and 5.7 ± 0.7 μmol/L) | NT | Bastimolide A (1) and B (2) (Fig. 5c) | Macrolide | Tropical marine cyanobacterium | Okeania hirsute | USA | [46] |
Active against stages/forms of P. falciparum; L. infantum amastigote (7.64 and 3.19 µmol/L) and promastigotes (28.1 and 7.42 µmol/L), and L. tropica promastigotes (20.28 and 7.08 µmol/L) | HMEC‐1 (62.19 ± 1.98 and 36.85 ± 5.79 µmol/L); THP‐1 (> 100 and 31.75 µmol/L) | Sesquiterpene avarone (1) and avarol (3) (Fig. 5d) | Quinone | Coast area sponge | Dysidea avara | Turkey | [47] |
L. amazonensis promastigotes forms (5.25 µg/ml) and intracellular amastigotes (18.18 µg/ml) | NT | Harzialactone A (Fig. 5e) | Lactone | Marine fungus | Paecilomyces sp. 7A22 | Brazil | [48] |
chloroquine-resistant P. falciparum 3D7 strain blood stage (3.0 μmol/L and NA) | RAW 264.7 cells and N2A cells (Not cytotoxic) | Halymeniaol (1) and cholesterol (2) (Fig. 5f) | Sterol | Arabian sea red alga | Halymenia floresii | India | [49] |
P. falciparum 3D7 strains blood stage (359 and 0.250 nmol/L) | NT | Kaimanol (1) and saringosterol (2) | Sterol | Marine marine sponge | Xestospongia sp. | Indonesia | [50] |