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El-Sawy, E.R.; Kirsch, G. Chemical Structures and Biological Activities of of Aplysinopsins. Encyclopedia. Available online: https://encyclopedia.pub/entry/43992 (accessed on 02 July 2024).
El-Sawy ER, Kirsch G. Chemical Structures and Biological Activities of of Aplysinopsins. Encyclopedia. Available at: https://encyclopedia.pub/entry/43992. Accessed July 02, 2024.
El-Sawy, Eslam R., Gilbert Kirsch. "Chemical Structures and Biological Activities of of Aplysinopsins" Encyclopedia, https://encyclopedia.pub/entry/43992 (accessed July 02, 2024).
El-Sawy, E.R., & Kirsch, G. (2023, May 08). Chemical Structures and Biological Activities of of Aplysinopsins. In Encyclopedia. https://encyclopedia.pub/entry/43992
El-Sawy, Eslam R. and Gilbert Kirsch. "Chemical Structures and Biological Activities of of Aplysinopsins." Encyclopedia. Web. 08 May, 2023.
Chemical Structures and Biological Activities of of Aplysinopsins
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This entry is adapted from the peer-reviewed paper 10.3390/md21050268

Marine products are among the most promising sources of biologically active molecules. Aplysinopsins, tryptophan-derived marine natural products, were isolated from different natural marine sources including sponges, stony corals (hard corals) especially genus scleractinian, as well as sea anemone, in addition to one nudibranch. Aplysinopsins were reported to be isolated from different marine organisms related to various geographic areas such as Pacific, Indonesia, Caribbean, and Mediterranean regions.

aplysinopsin sources synthesis bioactivity

1. Different Sources and Chemical Structures of Aplysinopsins

The chemical backbone of the natural aplysinopsins include a simple configuration of monomeric aplysinopsin-type structures and their brominated derivatives at the A ring, variation in the structure of the C ring, the presence and configuration of the C-8-C-1′ double bond, the oxidation state of the 2-aminoimidazoline fragment and N-alkylated at the B ring (Figure 1), in addition to the aplysinopsin dimers form.
Marinedrugs 21 00268 g001 550
Figure 1. The chemical configuration of monomeric aplysinopsin-type structures shows detailed segmentation of the rings, carbon numbering, and type of bonds.
Aplysinopsin, (E)-5-((1H-indol-3-yl)methylene)-2-imino-1,3-dimethylimidazo-li-din-4-one (1), was first isolated from the sponge genus Thorecta of the Australian Great Barrier Reef by Kazlauskas et al. [1]. Sequentially, aplysinopsin and its derivatives have been reported in many other marine organisms from various geographic areas (Table 1, Table 2, Table 3 and Table 4) [2].
Table 1. Monomeric aplysinopsin-type structures and their brominated derivatives.
Marinedrugs 21 00268 i001
Aplysinopsin Derivatives X1 X2 R1 R2 Y Source [Ref.]
Aplysinopsin (1) H H Me Me NH Thorecta sp. sponge Great Barrier Reef Australia [1], Verongia spengelli sponge Florida Keys [3], Dercitus sp. sponge Caribbean [4], Smenospongia aurea sponge Caribbean [5], Astroides calycularis anthozoan Mediterranean [6], Tubastraea aurea Japan scleractinian coral [7], Tubastraea sp. scleractinian coral Philippines [8], Radianthus kuekenthali sea anemone Japan [9], Aplysina sp. sponge Japan [10], Tubastraea faulkneri scleractinian coral Australia [11], Tubastraea sp. scleractinian Japane [12], Smenospongia sp. sponge Indo-Pacific reefs [13], and Verongula rigida sponge Florida Keys [14].
Isoaplysinopsin (2) H H H Me NMe Aplysina sp. sponge Japan [10] and Smenospongia aurea sponge Jamaica [15].
2′-de-N-methylaplysinopsin (3) H H H Me H Dercitus sp. sponge Caribbean [4], Tubastrea coccinea coral Hawaii [16], Phestilla melanobrachia mollusk [16], Dendrophyllia sp. scleractinian coral Philippines [8], Smenospongia aurea sponge Jamaica [15], Verongula rigida sponge Florida Keys [14].
Methylaplysinopsin
(4)		 H H Me Me NMe Aplysinopsis reticulata sponge Australia [2] and Smenospongia aurea sponge Jamaica [15].
4′-Demethyl-3′-N-methylaplysinopsin (5) H H Me H NMe Dendrophyllia sp. scleractinian coral Philippines [8] and Smenospongia aurea sponge Jamaica [15].
N-3′-ethyl-aplysinopsin (6) H H Me Et NMe Smenospongia aurea sponge Jamaica [15].
3′-Deimino-2′,4′-bis(demethyl)-3′-oxo-aplysinopsin (7) H H H H O Leptopsammia pruvoti scleractinian coral France [8].
3′-Deimino-3′oxoaplysinopsin
(8)		 H H Me Me O Thorecta sp. sponge Great Barrier Reef Australia [1] and Tubastraea sp. scleractinian coral Philippines [8].
6-Bromo-2′-de-N-methylaplysinopsin
(9)		 Br H Me H NH Dercitus sp. sponge Caribbean [4], Tubastrea coccinea coral Hawaii [16], Phestilla melanobrachia mollusk [16], Dendrophyllia sp. scleractinian coral Philippines [8], Tubastraea faulkneri scleractinian coral Australia [11], Smenospongia aurea sponge Jamaica [15], Hyrtios erecta sponge Japan [17].
6-Bromoaplysinopsin (10) Br H Me Me NH Tubastrea coccinea coral Hawaii [16], Smenospongia aurea sponge Caribbean [5], Astroides calycularis anthozoan Mediterranean [6], Radianthus kuekenthali sea anemone Japan [9], Tubastraea faulkneri scleractinian coral Australia [11], Smenospongia aurea sponge Jamaica [15], Smenospongia aurea sponge Florida Keys [14].
6-Bromo-4′-de-N-methylaplysinopsin (11) Br H H Me NH Smenospongia aurea sponge Caribbean [5].
6-Bromo-4′-demethyl-
3′-N-methyl-aplysinopsin (12)		 Br H H Me NMe Dendrophyllia sp. scleractinian coral Philippines [8].
5,6-Dibromo-2′-demethylaplysinopsin (13) Br Br Me H NH Hyrtios erecta sponge Japan [17].
6-Bromo-3′-deimino-2′,4′-bis(demethyl)-3′-
Oxoaplysinopsin (14)		 Br H H H O Smenospongia aurea sponge Caribbean [18] and Leptopsammia pruvoti scleractinian coral France [8].
6-Bromo-3′-deimino-3′-oxoaplysinopsin
(15)		 Br H Me Me O Astroides calycularis anthozoan Mediterranean [6] and Tubastraea sp. scleractinian coral Philippines [8].
Table 2. Aplysinopsins substituted at the nitrogen atom.
Marinedrugs 21 00268 i002
Aplysinopsin Derivatives X R Sources [Ref.]
N-propionylaplysinopsin (16) H OCCH2CH3 Astroides calycularis anthozoan Mediterranean [6].
6-Bromo-N-propionylaplysinopsin (17) Br OCCH2CH3
N-methylaplysinopsin (18) H CH3 Aplysina sp. sponge Japan [10].
Table 3. Aplysinopsins with a single C-8-C-1′ bond.
Marinedrugs 21 00268 i003
Aplysinopsin Derivatives R X Sources [Ref.]
1′,8-Dihydroaplysinopsin (19) H H Tubastrea coccinea coral Hawaii [16], Radianthus kuekenthali sea anemone Japan [9], and Thorectandra sp. sponge Indo-Pacific reefs [13].
6-Bromo-1′,8-dihydroaplysinopsin (20) Br H
6-Bromo-1-hydroxy-1′,8-dihydroaplysinopsin (21) Br OH Thorectandra sp. sponge Indo-Pacific reefs [13].
6-Bromo-1-methoxy-1′,8-dihydroaplysinopsin (22) Br OCH3
6-Bromo-1-ethoxy-1′,8-dihydroaplysinopsin (23) Br OCH2CH3
Table 4. Aplysinopsin dimers.
Marinedrugs 21 00268 i004
Aplysinopsin Dimers Sources [Ref.]
Cycloaplysinopsin (24) Scleractinian corals of the family Dendrophylliidae from Comoro islands and hard coral Tubastraea sp., from the Great Hanish in the Archipelago of the Hanish Islands, Yemen, tropical Indo-Pacific (Comoros, Philippines) scleractinian corals of the family Dendrophylliidae [19][20].
Tubastrindoles A–C (25) Stony Coral, Tubastraea sp. scleractinian Japane [12].
Tubastrindole B (26) Australian Marine Sponge, a specimen of the sponge Ianthella cf. flabelliformis [21].
Tubastrindoles D–H (27) Stony Coral, Tubastraea aurea Odomari area, Kagoshima Prefecture, Japan [22].
Dictazolines A and B Marine Sponge Smenospongia cerebriformis, Hospital Point on Solarte Isle, Boca del Toro, on the northwest coast of Panama [23].
Dictazolines C–E (28) and
Dictazoles A and B (29)		 Marine Sponge Smenospongia cerebriformis, Panamanian sponge [24].

2. Biological Activity

Aplysinopsins possess an array of biological activities (Table 5).
Table 5. Biological activities of aplysinopsins.
Aplysinopsin Derivatives Activity [Ref.]
Aplysinopsin (1) - CNS permeable scaffold for dual inhibition of cholinesterase and BACE-1 inhibition [25][26].
- Possess monoamine oxidase (MAO) inhibitory activity (IC50 of 5.6 nM) [27].
- Antiplasmodial activity (IC50: 0.43 µg/mL) [28].
- Antineoplastic activity (IC50 values against L-1210 and KB cells, respectively, 2.3 and 6.4 µg/mL [3][10].
- Inhibit the growth of Staphylococcus epidermidis [13].
- An inhibitor of development of fertilized sea urchin eggs at 2.5 µg/mL [7].
- Induce symbiosis between sea anemone and anemonefish [9].
Isoaplysinopsin (2) - Showed cytotoxic against murine lymphoma L-1210 (IC50 11.5 µg/mL) and human epidermoid carcinoma KJ3 (31% inhibition at 20 µg/mL) cells [10].
Methylaplysinopsin (4) - Antidepressant activity by enhancing serotonin activity in the central nervous system [29][30].
- Inhibition of monoamine oxidase (MAO) [30].
- Showed cytotoxicity (IC50 values against L-1210 and KB cells of 3.5 and 6.7 µg/mL, respectively) [10].
N-3′-ethyl-aplysinopsin (6) - Serotonin receptors modulator with Ki value 1.7 µM to the 5-HT2A and 3.5 µM to 5-HT2C serotonin subtypes [15].
6-Bromo-2′-de-N-methylaplysinopsin (9) - Serotonin receptors modulator (showed significant selectivity to the 5-HT2C serotonin subtype over the 5-HT2A subtype) [15].
- Antiplasmodial.
- Inhibitor of nitric oxide synthase (nNOS).
6-Bromoaplysinopsin (10) - Serotonin receptors modulator (showed highest affinity to 5-HT2C with a Ki value similar to that of serotonin 0.33 µM) [15].
5,6-Dibromo-2′-demethylaplysinopsin (13) - Inhibitor of nitric oxide synthase (nNOS) [17].
6-Bromo-3′-deimino-3′-oxoaply-sinopsin (15) - Antiplasmodial activity [20].
1′,8-Dihydroaplysinopsin (19) - Induce symbiosis between sea anemone and anemonefish [9].
6-Bromo-1′,8-dihydroaplysinopsin (20)
6-Bromo-1-hydroxy-1′,8-dihydroaplysinopsin (21)
6-Bromo-1-methoxy-1′,8-dihydroaplysinopsin (22)
6-Bromo-1-ethoxy-1′,8-dihydroaplysinopsin (23)		 - Inhibit the growth of Staphylococcus epidermidis [13].

References

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  27. Lewellyn, K.; Bialonska, D.; Loria, M.J.; White, S.W.; Sufka, K.J.; Zjawiony, J.K. In vitro structure–activity relationships of aplysinopsin analogs and their in vivo evaluation in the chick anxiety–depression model. Bioorganic Med. Chem. 2013, 21, 7083–7090.
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  30. Baird-Lambert, J.; Davis, P.A.; Taylor, K.M. Methylaplysinopsin: A natural product of marine origin with effects on serotonergic neurotransmission. Clin. Exp. Pharmacol. Physiol. 1982, 9, 203–212.
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Eslam R. El-Sawy
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