Indian Journal of Chemistry Vol. 39B, October 2000, pp. 723 - 733

Review Article

Chemical constituents and their biological activities of the sponge family Aplysinellidae: A reviewt

M Rarna Rao, U Venkatesham, K V Sridevi & Y Venkateswarlu* Natural Products Laboratory, Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 D07,

India

Bromo tyrosine derived metabolites are a group of alkaloids, frequently encountered in the sponges of the order Verongida. Several bromotyrosine derived alkaloids have been isolated from the sponges family Aplysinellidae (order Verongida) with varied biological activities. A concise review of the family of the sponges Aplysinellidae has been summarized till June 1 999 that have been abstracted in chemical abstracts.

The chemistry of marine natural products has been reviewed time to time covering the literature on isolation and biological activity of second� metabolites from marine flora and fauna. J A literature survey revealed that the sponges yielded compounds with unique structural features and high biological activities. Among these species, the sponges of the order Verongida, family Aplysinellidae has largely produced (95%) bromine containing secondary metabolites. The present review covers the literature till June 1 999 abstracted in chemical abstracts on isolation and biological activities of the secondary metabolites the sponges of the family Aplysinellidae.

The family Aplysinellidae is further subdivided in the following way. Aplysinellidae

(i) Psammaplysilla : (a) P. arabica; (b) P. purea; (c) P. purpurea; (ii) Pseudoceratina: (a) P. crassa; (b) P. purpurea; (c) P. verrucosa.

Chemical constituents of the genus Psammaplysilla Very early studies by Chang et al 2 on the sponge

Psammaplysilla purpurea afforded a dibromotyrosine derived metabolite, 2-hydroxy-3,5-dibromo-4-methoxyphenyl acetamide 1 and characterized through interpretation of spectral data. In 1 978, Ayanoglu et al 3 reported four sterols, aplysterol 2, 3�-hydroxy-26,27-bis norcholest-5-en-24-one 3, 3�hydroxy pregna-5-en-20-one 4 and 3�-hydroxy-5apregnan-20-one 5 along with the usual sterols in minor amounts . Later compound 3 was also synthesized. Rotem et al 4 isolated two new bromo

t liCT Communication No. 4308

metabolites 6 and 7 from the sponge P. purea. The structures of 6 and 7 have been elucidated by using spectroscopic methods and chemical degradation. Two new antimicrobi.li constituents psammaplysin-A 8 and psammaplysin-B 9 were isolated from a Palau sponge P. purea by Roll et al. 5 These two compounds were characterized by spectroscopic analysis. The structure of compound 8 was further confirmed by single crystal X-ray diffraction studies on acetamide acetate 8a. Biogenetically the psammaplysins 8 and 9 are derived from dibromotyrosine via benzene oxideoxepin intermediates. Compounds 8 and 9 were reported as antimicrobial constituents.

The FA'BMS of the known metabolites of aerophobin- l 10 and aerophobin-2 1 1 have been discussed in detail by Cimino et al.6 Nakamura et al isolated a novel secondary metabolite purealin 12 from the Okinawan sponge P. purea and the structure . 1, J I d J H J3C was determmed by H- H homonuc ear an -heteronuclear NMR chemical shift correlations and CD spectra.7 Purealin 12 moderates enzymic reactions of ATPases. Subsequently lipopurealins-A, B, and C 13-15 have been isolated from the Okinawan marine sponge P. purea by Wu et al. 8 and the structures were elucidated on the basis of spectral data. Compounds 13-15 are inhibitors of Na, K-ATPase .

Purealin 16, a novel stabilizer of smooth muscle myosin filaments that modulates- ATPase activity of dephosphorilated myosin, has been isolated from the sponge P. purea by Takito et al.9 The structure of compound 16 was established on the basis of spectral studies. Demethoxy derivative of purealin, 17 activates myosin EDTA-ATPase at 0.3-30 Jlm and inhibited myosin Ca-ATPase and Na+, K+-ATPase

724 INDIAN J CHEM, SEC B, OCTO BER 2000

o 2

HO

Br�R2 r:j.HR, 1 .&

YHN�o Bf

6 R, = R2 = R3 = H 7 R, = R3 = H. � = OH

S R, = R2 = H Sa R, = Ac. R, = H 9 R, = H. R, = OH 9a R, = Ac. R2 = H

12 �e Br Br HO -:r ... 1 �. 13 0 �X

14 0

3

5

y .

OM

10 X = H 11 X = NH,

'f'YX f5 0

RAO et af. : CHEMICAL CONSTITUENTS OF APL YSINELLIIDAE 725

Br Br . -9" . Yo 1 . . " MeO' q� . ..... , lit \ -

H 0:CvyNOH. H 1 0 N�N

Mo 0 Br

\l }--NH, Y 16 0 � . Br Br -9" 1 , •... 1040 '" ft. q. '" � \ d it .--. �0.:Cuy N y """"""' '''''''''''' 1 -...:::: NOH o 0 � N Br

0 L�NH' was isolated from the sponge P. purpurea by'

Nakamura et al. 10. 1 1

The cytotoxic extract of the sponge Psammaplysilla sp. from Tonga contains the monobromotyrosine-deri vati ves, 3-bromo-4-hydroxyphenylacetonitrile 18 and psammaplysin-A 19, containing a disulfide bridge. 1

2 These compounds

18 and 19 were characterized by the study of their spectral data. Longeon et al 13 isolated araplysillins I and II 20 and 21 from the sponge P. arabica and their structures were elucidated by spectroscopic methods. Compounds 20 and 21 inhibited of Na+/K+-ATPase and had antimicrobial activity. Three new bromotyrosine-cysteine derivatives, psammaplins B , C and D 22-24 including 3-bromo-4-hydroxybenzene aldehyde 25 and 3-bromo-4-hydroxyphenyl acetonitrile 18 were isolated from the sponge P. purpurea. These compounds were characterized through the interpretation of spectral data. Psammaplin D showed antimicrobial and mild tyrosine kinase inhibitory activity. 1

4

Purealidin-A 26, a new cytotoxic bromotyrosinederived alkaloid was isolated from the Okinawan marine sponge P. pureal5 and its chemical structure elucidated on the basis of spectroscopic data. Purealidin-A 26 is promising antileukemic activity. Later, Kobayashi et a/16 reported purealidins B and C 27 and 28 from the Okinawan marine sponge P. purea and their structures were elucidated on the basis of spectroscopic data. Compound 27 showed antibacterial activity while compound 28 exhibited antifungal and antineoplastic activities. Two new tyrosine derived metabolites, 14-debromo araplysillin 29 and 14-debromo prearaplysillin 30 together with

17 H

the known compound araplysillin 31 have been isolated from the sponge Druinella = Psammaplysilla purpurea by James et al. 1 7 Purealidin D 32 and purealidins E-G (33-35) were isolated from the Ok

· . . P b T d I 1 8. 1 9 . maw an· manne sponge . purea y su a et a

and their structures were elucidated on the basis of spectroscopic data.

Copp et al. 20 isolated a new cytotoxic dibromotyrosine-derived metabolite psammaplysin-c 36 along with two known psammaplysins A and B . All these compounds were found to possess moderate in vitro �ytotoxicity towards the human colon tumor cell line HCT 1 16. A new macrocyc1ic peptide, bastadin 2 37 and the previously reported bastadins 5, 7 and 1 2 (38-40) were isolated from the sponge P. purpurea collected at Phonpei by Carney et ae l Compound 40 is mildly cytotoxic against several cell l ines and inhibits the enzymes topoisomerase II and dehydrofolate reductase . Nine new bromotyrosine derived metabolites, purpuramines A-I (41-49) were isolated from the marine sponge P. purpurea22. and their structures were determined by the interpretation of spectral data. Compounds 41-49 exhibited antibacterial activity against Staphylococcus aurells.

Three new cytotoxic bromotyrosine-derived secondary metabolites, aplysamines 3, 4 and 5 (50-52) were isolated from the sponge P. purpurea by Jurek et

. al 23 and characterized by the interpretation of spectral data. In 1 994, Pakrashi et at 24 reported two new bromotyrosine-derived metabol ites (53 and 54) from the sponge P. purpurea collected from Bay of Bengal and the structures assigned . on the basis of spectroscopic analysis on their acetates (53a and 54a). Honma et at 25 reported two new guanidine alkaloids,

726 OCTOBER 2000 M SEC B, INDIAN J CHE ,

.� � 18

Br

OH

N H � �s-s-V

19 ty Br � I� ,-HO � ""� W _�O . I ·-";;::;: .. "If' I 6 NHR, o Br 20 R, = H ,.. ... -(CH,).-CH(CH:J, 21 R, = CO-�'2

�R N H

�. X

22 R = SCN

o H 25

23 R = SO,NH, HCOOMe 24 R = S,CH,N

���r� . 26

.+ . HO ���'" � \- H 0 � I 6 �CH,J, o Br o ......... NOH �Br

Br

� ..... � -..;;::;: . I b o �o� 21 -}Y' �

29 R = H oo� , 0 '" " ' 0 '. � t 6 NH, R

RAO et at. : CHEMICAL CONSTITUENTS OF APLYSINELLIIDAE

32

OOCCF, .... �O

33

Rl�O�� I A Br 112

37 X = Sr, Y = Sr, R = H 39 X = H, Y = Br, R = H

H N�N)-

Ifl, o · \LN H

+ - + 34 R, = NH,Me q R, = NHMe, CI .. - + -35 R, = NHMe, q R, = NH,Me CI

8r�W � I �

�

HO�O

X Dr

� I :::,... Br H H I H ,

38 W = H, X = H, Y = Br OH

� W = OH, X = Br, Y = H

.,. R, = Br, R, = NH,

42 R, = H, R,:NH'0 , "I:: 43 R, = Br, R, = -N + �

.. R = H

46 R, = H , R, = H .7 R, = H, R, = C H, 46 R , = CH" R, = H ., R, = CH,. R, = CH,

727

728 INDIAN J CHEM, SEC B, OCTOBER 2000

S7 X = CO(CH,),-CH=CH-(CH,).-CH(CH3), 58 X = CO-{CH')11-CH3

aplysillamides A and B (55 and 56) from the marine sponge P. purea and the structures elucidated on the basis of spectroscopic data. Compounds 55 and 56 are having antimicrobial activity.

Lipopurealins D and E (57 and 58) and purealidin H (59) were isolated from the Okinawan marine sponge P. purea by Kobayashi et at 26 and the structures were elucidated on the basis of 2D NMR and FABMSIMS data. Further, Kobayashi et aF7 reported nine bromotyrosine alkaloids, purealidins JR (60-68) from the sponge P. purea. Pureal idins N, P and Q (64, 66 and 67) are cytotoxic to tumor cell lines, while purealidins J, K, P and Q (60, 61, 66 and 67) showed moderate inhibitory activity against epidermal growth factor (EGF) receptor kinase. Venkateswarlu et aP8 isolated three compounds, 3,5-

dibromo-4-methoxyphenyacetonitrile 69, 3,5-dibromo-4-methoxybenzoic acid 70 and 3-bromo-4-methoxyphenyl acetonitrile 71 from the sponge P. purpurea collected from Tuticonn coast India, and characterized through the spectral data. New bromotyrosine alkaloids, purealidins A-R have been isolated from an Okinawan marine sponge P. purea by Kobayashi et at and their structures were elucidated on the basis of spectroscopic data.29 Venkateswarlu and his co_workers30.3 1 .32 isolated four new bromo-tyrosine derived metabolites 72-75 and the known compounds' 'molaka' iamine 764, 2,6-dibromo-4-hydroxy-4-ac�iamido- l , I -dimethoxy-2,5-cyclohexadiene 7743, aerothionin 7844, bastadin-6 7945, bastadin- 1 6 8046, purealidin P 6627, purealidin G 3519 and aplysamine-2 8147 from the sponge P.

Br

Br

RAO et a/. : CHEMICAL CONSTITUENTS OF APLYSINELLIIDAE

OMe

OMe

8r

He

Br

HO

NH � I I �N�NH H '

Br

Br

B

� H �'l-N

� o 61 0 �

�L

N \ 'l-R o N 63 R = NH� X " OH H

64 R = H, X = OH

��O,� o 66 8r�N(CH,)'

Bf

OM.

OM.

69 R, = Br, R, = CH,CN 70 R, = Br, R, = COOH 71 R, = H, R, = CH,CN

729

730

,..

Br

HO

INDIAN J CHEM, SEC B, OCTOBER 2000

. '-':::: Br�R

' .0 �O 75 R = NHz Br 75a R = NHAc

Br�,-,:::: N� H N�O .0 z

Br 76

NH,

OMe

Br purpurea collected from Mandapam coast, India. All these compounds were characterized through the interpretation of spectral data.

o

H N�N

H

78

OH /

:RJ��. HO�, Br , "=::: OHBr � 0 h

R N H

OH

79 R = Br 80 R = H

N(CH,),H+X.

Chemical constituents of the genus Pseudoceratina:

Br�N ,Jl) llOH H CH,o 81

So far th�re are onl.y few r��o�s on the genus Pseudoceratma. Faulkner et aL. - · In 199 1 reported two new dibromotyrosine derived metabolites 82 and 83 from the Caribbean sponge P. crassa . The structures were proposed on the basis of spectroscopic evidences and were confirmed by synthesis. In 1 993, Costantino et al. 34 reported unique five membered glycolipids, crasserides 84-89, from the sponge P. crassa. Their structures were determined by spectroscopic and chemical methods. A new triterpene 90 and four new bromotyrosine derived metabolites 91-94 have been isolated from the Caribbean sponge P. crassa by Ciminiello et al.35 and their structures were determined by spectroscopic analysis. Ciminiello et al.36 reported three more new brominated metabolites 95-97 from the sponge P. crassa and the structures were determined on the basis of spectral methods. The bromo compounds of P. crassa can be used as chemical markers to support the identification of sponge based on morphological characters.

A detailed analysis of a Carribbean specimen of Pseudoceratina sp. yielded brominated products 98 and 99 which were characterized on the basis of spectral analysis. Compounds 98 and 99 which are the major brominated metabolites of the specimen and which have not yet been isolated from any Pseudoceratina sp. could be usefully employed as

, '-':::: Br�COOR

(CH,l2N�O .0 Br

82 R = Et 83 R = H

RAO et at. : CHEMICAL CONSTITUENTS OF APL YSINELLJIDAE

��O H OR, 010, H o 'S R, . H, R2 •

II R, . H, R2 •

• 7 R, · H, R2 •

88 R, . H, R, E

�"-':: NOH H � N�

I JNH o N� M

OMe

";Jy " HO·····X �==Z COOH

98

OMe ";Jy" HO·····X ' d

H �

N yNLrNH2 H 100

8.

BrX(J!:N(CH,l3 I � COO>

RO

X

91 R = X : H 92 R : H, X = Br 93 R : Me, X : H N R : Me, X : Br

Meo�. COO-I +N

HO � / 'CH,

OMe

87 H,C 99

8.

+ ... NMe3 f�)--NH'

N�N H H 1 0 1

73 1

732 INDIAN J CHEM, SEC B, OCTO BER 2000

OMe sr:Qr" . �

I Sr

" HO 0 .••••• " �=Y��O

o

$: O�NJlCN I H � �N fu 104

105 R = CHO 106 R E CO(CH'}l1CHMe,

OM. Br

1 07

Sr 102

103

chemotaxonomic markers·H. Benharref et al. J8 reported three new bromotyrosine derived alkaloids, pseudoceratinamines A, B and C (100-102) from the sponge P. verrucosa in 1 996. The structures and absolute configuration of these compounds were e lucidated by spectral methods. A new spermidine,

Sr

pseudoceratidin 103 with two 4,5-dibromopyrrole-2-carbamyl units was reported from sponge Pseudoceratina purpurea by Tsukamoto et al.J9 Its structure was elucidated on the basi s of spectral data. Compound 103 inhibited larval settlement and metamorphosis of the barnacle Balanus amphitrite with on ED50 value of 8.0 Ilg/mL.

Tsukamoto et al.4o reported an unprecedented antifouling cyanoformamide derivative pseudoceratinamine 104 from the sponge P. purpurea. Its structure was elucidated on the basis of spectral and chemical evidences. Two new bromotyrosine derivatives ceratinamides A and B 105 and 106, have been isolated from the sponge P. purpurea by Tsukamoto et al.4 1 These compounds inhibited larval settlement and metamorphosis of the barnacle Balanus amphitrite with ED50 values of 0. 1-0.8 Ilg/mL.

Breakman et al.42 reported a novel antifouling tyrosine alkaloid 5-bromo verongamine 107 from Caribbean sea specimen of the sponge Pseudoceratina sp. Its structure was determined on the basis of spectral data.

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- RAO et af.: CHEMI CAL CONSTITUENTS OF APL y'SINELLIIDAE 733

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