A new amide from the marine sponge Haliclona baeri

Article abstract of DOI:10.1080/14786419.2021.1941950

A new amide, baeriamide (1), along with nine known diketopiperazines (2-10), was isolated from the marine sponge Haliclona baeri. Their structures were identified by the means of UV, IR, MS and NMR. The absolute configuration of 1 was established by Marfey’s method and comparing the specific optical rotation with the known compound HCO-Val-Gly methyl ester. Compound 1 was derived from dehydration of formylated L-valine with γ-amino-butanoic acid methyl ester. Compounds 2-10 were isolated from the genus of Haliclona for the first time. The absolute confirmation of 7 was confirmed first by the means of single-crystal X-ray diffraction. The cytotoxic, antibacterial, antiviral and antifouling activities of these compounds were also tested. However, none of them exhibited significant bioactivities.

Full text of DOI:10.1080/14786419.2021.1941950

Natural Product Research
Formerly Natural Product Letters
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gnpl20
A new amide from the marine sponge Haliclona
baeri
Yan-Fang Xiao, Jia-Yi Xu, Le-Zhi Cui, Can-Bin Wang, Yu Lei, Xiao-Jian Liao, Shi-
Hai Xu & Bing-Xin Zhao
To cite this article: Yan-Fang Xiao, Jia-Yi Xu, Le-Zhi Cui, Can-Bin Wang, Yu Lei, Xiao-Jian Liao,
Shi-Hai Xu & Bing-Xin Zhao (2021): A new amide from the marine sponge Haliclonaꢀbaeri, Natural
Product Research, DOI: 10.1080/14786419.2021.1941950
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NATURAL PRODUCT RESEARCH
https://doi.org/10.1080/14786419.2021.1941950
A new amide from the marine sponge Haliclona baeri
ꢀ
ꢀ
Yan-Fang Xiao , Jia-Yi Xu , Le-Zhi Cui, Can-Bin Wang, Yu Lei, Xiao-Jian Liao,
Shi-Hai Xu and Bing-Xin Zhao
Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou,
Guangdong, P. R. China
ABSTRACT
ARTICLE HISTORY
A new amide, baeriamide (1), along with nine known diketopiper-
azines (2-10), was isolated from the marine sponge Haliclona
baeri. Their structures were identified by the means of UV, IR, MS
and NMR. The absolute configuration of 1 was established by
Marfey’s method and comparing the specific optical rotation with
the known compound HCO-Val-Gly methyl ester. Compound 1
was derived from dehydration of formylated L-valine with
c-amino-butanoic acid methyl ester. Compounds 2-10 were iso-
lated from the genus of Haliclona for the first time. The absolute
confirmation of 7 was confirmed first by the means of single-crys-
tal X-ray diffraction. The cytotoxic, antibacterial, antiviral and anti-
fouling activities of these compounds were also tested. However,
none of them exhibited significant bioactivities.
Received 11 March 2021
Accepted 6 June 2021
KEYWORDS
Sponge; Haliclona
baeri; amide
1. Introduction
The marine sponges of genus Haliclona, belonging to the family Chalinidae, were
mainly discovered in Mediterranean Sea (Defant et al. 2011; Nuzzo et al. 2012; Genta-
Jouve and Thomas 2013), Arctic Ocean (K o€ ck et al. 2013), Pacific Ocean (Casapullo
et al. 2009) and South China Sea (Kong et al. 2016; Chen et al. 2017). The genus of
Haliclona contained over 600 species (Zhu et al. 2019), most of which had been widely
investigated since1970s (Bach et al. 1978). Previous studies on chemical constituents
of this genus led to different types of compounds, most of which were nitrogenous
compounds, including amides (Wang, Lee et al. 2009), cyclic peptides (Rashid et al.
2000; Randazzo et al. 2001), alkaloids (Einarsdottir et al. 2017; Zhu et al. 2019),
CONTACT Bing-Xin Zhao
zbx840622@163.com; Shi-Hai Xu
txush@jnu.edu.cn; Xiao-Jian Liao
tliaoxj@jnu.edu.cn
ꢀ
These authors contributed equally to this work.
Supplemental data for this article can be accessed online at https://doi.org/10.1080/14786419.2021.1941950.
ß 2021 Informa UK Limited, trading as Taylor & Francis Group

2
Y.-F. XIAO ET AL.
Figure 1. Structures of 1-10 isolated from H. baeri.
nulcleosides (Wang, Dong et al. 2009) and glycosphingolipids (Ayyad et al. 2009).
Moreover, some of them exhibited a variety of biological activities such as antifouling
(Sera et al. 2003), cytotoxic (Reyes et al. 2007) and antimicrobial (Arai et al. 2009). It
was worth mentioning that Marfey’s method was always used to determine the abso-
lute configurations of amino acid residues in these nitrogenous compounds. Briefly, a
mixture of D- and L-amino acids could be separated by HPLC after derivation with
Marfey’s reagent so that we could compare the retention time of the derivative of
amino acid residue with the derivative of standard D- and L-amino acid (Marfey 1984;
Khedr et al. 2013). So far, only one literature about the chemical constituents investi-
gation of Haliclona baeri had been reported (Wattanadilok et al. 2007).
In our ongoing search for new bioactive marine natural products from the sponges
(Liang, Liao, Lin, et al. 2019; Liang, Liao, Zhao, et al. 2019; Liang et al. 2020; Zhang
et al. 2020), 10 nitrogenous compounds, including a new amide, baeriamide (1),
together with nine known diketopiperazines (2-10) had been isolated from H. baeri
(Figure 1). Compound 1 was derived from dehydration of formylated L-valine with
c-amino-butanoic acid methyl ester. Compounds 2-10 were isolated from the genus of
Haliclona for the first time. Herein, we described the isolation, structure identification
and biological activities of these compounds.
2. Results and discussion
Baeriamide (1) was isolated as white powders. The molecular formula of 1 was deter-
þ
mined as C H N O by HR-ESI-MS at m/z 267.1310 [M þ Na]
(calcd for
1
1 20 2 4
C H N O Na: 267.1315) The IR bands of 1 indicated the presence of aldehyde group
2875 cm ) and carbonyl groups (1731 and 1651 cm ). The NMR spectra of 1
1
1 20 2 4
ꢁ
1
ꢁ1
(
revealed that 1 possessed two carbonyls [d 175.3, and 173.3], an aldehyde group [d
C
H
0
8
.11 (br s, CHO); d 163.7], two methines [d 4.19 (d, J ¼ 6.6 Hz, H-2 ) and 2.06 (m, H-
C
H

NATURAL PRODUCT RESEARCH
3
0
3
3
); d 58.8 and 31.9], a methoxyl [dH 3.65 (s, OCH ); d 52.1], three methylenes [d
C
3
C
H
.22 (td, J ¼ 6.6, 1.2 Hz, H-4), 2.36 (t, J ¼ 7.2 Hz, H-2) and 1.79 (m, H-3); d 39.6, 32.0
C
0
0
and 25.6] and two methyl [d 0.95 (d, J ¼ 6.6 Hz, H-5 ) and 0.93 (d, J ¼ 6.6 Hz, H-4 ); d
H
C
1
9.7 and 18.3]. With the aid of 1 D and 2 D NMR experiments, the full assignment of
protons and carbon signals of 1 were shown in Table S1.
1
1
The comprehensive analysis of H- H COSY correlations of 1 displayed two spin
coupling systems in bold as shown in Figure S1. In the HMBC spectrum, the correla-
0
0
0
0
tions between CHO and C-2 , between H-2 /H-3 and C-1 indicated the presence of
formylated valine moiety. The correlations between H-2/H-3/OCH and C-1 verified the
3
establishment of c-amino-butanoic acid methyl ester unit. In addition, the HMBC cor-
0
relation between H-4 and C-1 together with the molecular formula information sug-
gested that the units of formyl valine and c-amino-butanoic acid methyl ester were
connected by amido bond. Thus, the planar structure of 1 was deduced.
The absolute configuration of 1 was determined by Marfey’s method. HPLC-HRMS
analysis of the Na-(5-fluoro-2,4-dinitrophenyl)-L-leucinamide (FDLA) derivative of the
hydrolysate of 1 gave the same retention time as the FDLA derivative of standard L-
valine. (Marfey 1984; Khedr et al. 2013). Thus, the stereochemistry of 1 was elucidated
as S, which was further confirmed by comparing the specific optical rotation of 1 with
that of the similar compound HCO-Val-Gly methyl ester (Ranjalahy-rasoloarijao
et al. 1989).
The nine known compounds were elucidated as cyclo (D-6-Hyp-L-Ile) (2) (Yang et al.
2
2
016), bacillusamide B (3) (Yonezawa et al. 2011), staphyloamide B (4) (Khedr et al.
013), cyclo(L-Pro-L-Val) (5) (Furtado et al. 2005; Pedras et al. 2005), cyclo (L-Pro-L-Leu)
(
(
6) (Li et al. 2013), cyclo (L-6-Hyp-L-Leu) (7) (Li et al. 2011) and cyclo (L-Pro-L-Phe) (8)
Wang et al. 2010; Xie et al. 2018), cyclo (D-6-Hyp-L-Phe) (9) (Park et al. 2006) and
cyclo (L-Pro-L-Tyr) (10) (Jayatilake et al. 1996) by comparing their spectroscopic data
with those reported in literatures. The absolute configuration of 7 was firstly con-
firmed by the means of single-crystal X-ray diffraction with suitable Flack parameter of
0.03 (11). Compounds 1-10 were test for cytotoxic activities against K562 and A549
human cancer cell lines (Liang, Liao, Lin, et al. 2019), antibacterial activities against
Escherichia coli and Salmonella (Ukwueze et al. 2015), antiviral activities against herpes
simplex virus (HSV-1) (Wu et al. 2020) as well as antifouling activities against bryozo-
ans (Wang et al. 2017). However, none of them exhibited significant inhibi-
tory activities.
3. Experimental
3.1. General experimental procedures
Optical rotations were detected using P-2000 Digital Polarimeter (JASCO International
Co. Ltd., Hachioji, Japan). The IR and UV spectra were performed on a Shimadzu UV-
2
(
6
401PC spectrometer (Shimadzu, Kyoto, Japan) and an IR Affinity-1 spectrometer
Shimadzu, Kyoto, Japan), respectively. The NMR spectra were recorded on a Bruker Av
00 NMR spectrometer. HR-ESI-MS was carried out on an AB SCIEX 500 R QTOF mass
spectrometer. HPLC-HRMS [Rp-C : 4.6 ꢂ 250 mm i.d 5 lm (Cosmosil, Nacalai, Japan)]
18
was generated using Agilent 1290LC-6545 QTOF mass spectrometer. Preparative HPLC

4
Y.-F. XIAO ET AL.
[
Rp-C : 20 ꢂ 250 mm i.d 5 lm (Cosmosil, Nacalai, Japan)] and semi-preparative HPLC
1
8
[Rp-C : 10 ꢂ 250 mm i.d 5 lm (Cosmosil, Nacalai, Japan)] was performed on an Agilent
1
8
1
200 series apparatus (Agilent, Palo Alto, America). Silica gel (300-400 mesh, Qingdao
Marine Chemical Co., Qingdao, China) and Sephadex LH-20 (GE Healthcare, Uppsala,
Sweden) were used for column chromatography. The thin-layer chromatography was
accomplished by precoated silica gel plates (HSGF-254, Qingdao Marine Chemical
Factory, Qingdao, China).
3.2. Material
The sponge was collected from Xuwen County, Zhanjiang City, Guangdong Province,
China, in May 2017, which was identified by Prof. De-Xiang Wang as H. baeri. The spe-
cimen (2017-C) had been deposited in the Department of Chemistry, College of
Chemistry and Materials Science, Jinan University.
3.3. Extraction and isolation
The dried and powdered sponge H. baeri (20.0 kg) was extracted totally with 95%
EtOH at room temperature to obtain the crude extract (778.0 g). The extract was sus-
pended in water and partitioned with EtOAc and n-butanol successively to afford two
corresponding portions. The EtOAc extract (174.0 g) was subjected to silica gel column
(
9
1
U 150 mm ꢂ l200 mm) with gradient elution using cyclohexane/acetone (100:0, 99:1,
8:2, 97:3, 96:4, 95:5, 93:7, 90:10, 80:20, 70:30, 50:50, 0:100) to yield 12 fractions (Frs.
ꢃ 12). Fr. 9 (6.6 g) was applied to silica gel column (U 60 mm ꢂ 800 mm) eluted with
CH Cl /CH OH (100:0, 99:1, 98:2, 97:3, 96:4, 95:5, 93:7, 90:10, 80:20, 70:30, 50:50, 0:100)
2
2
3
to gain 4 fractions (Frs. 9-1 ꢃ 9-4). Fr. 9-2 (2.3 g) was separated by Sephadex LH-20 col-
umn (U 30 mm ꢂ 1700 mm) with CH Cl /CH OH (1:1, 1 mL/min) to give Frs. 9-2-1 ꢃ 9-
2
2
3
2
-8. Fr. 9-2-3 (907.9 mg) was subjected to silica gel column (U 20 mm ꢂ 400 mm) and
eluted with petroleum ether/EtOAc (100:0, 99:1, 98:2, 97:3, 96:4, 95:5, 93:7, 90:10,
0:20, 70:30, 50:50, 0:100) to give 9 fractions (Frs. 9-2-3-1 ꢃ 9-2-3-9). Further purifica-
tion of Fr. 9-2-3-9 (489.6 mg) was performed by preparative reversed-phase HPLC
8
(
2
3
6 mL/min, CH OH/H O ¼ 30:70) to give 3 (7.8 mg, t ¼ 13.1 min), 7 (23.6 mg, t ¼
3
2
R
R
4.0 min) and other 3 fractions (Frs. 9-2-3-9-1 ꢃ 9-2-3-9-3). Compounds 2 (14.5 mg, t ¼
R
2.1 min), 4 (4.6 mg, t ¼ 41.7 min) and 5 (12.0 mg, t ¼ 45.5 min) were isolated by
R
R
semi-preparative reversed-phase HPLC (2 mL/min, CH OH/H O ¼ 30:70) from Fr. 9-2-3-
3
2
9
-1 (37.5 mg). Fr. 9-2-3-9-2 (13.1 mg) was purified by semi-preparative reversed-phase
HPLC (2 mL/min, CH OH/H O ¼ 13:87) to obtain 1 (1.7 mg, t ¼ 59.6 min) and 8
3
2
R
(
2
1
6.9 mg, t ¼ 57.4 min). Compound 9 (6.5 mg, t ¼ 28.5 min) was obtained from Fr. 9-
R
R
-3-9-3 (34.8 mg) by semi-preparative reversed-phase HPLC (2 mL/min, CH CN/H O ¼
3
2
0:90). Fr. 9-3 (2.1 g) was subjected to Sephadex LH-20 column (U 30 mm ꢂ1700 mm)
with CH Cl /CH OH (1:1, 1 mL/min) to give Frs. 9-3-1 ꢃ 9-3-6. Fr. 9-3-3 (754.0 mg) was
2
2
3
chromatographed on silica gel column (U 20 mm ꢂ 400 mm) eluting with petroleum
ether/EtOAc (100:0, 99:1, 98:2, 97:3, 96:4, 95:5, 93:7, 90:10, 80:20, 70:30, 50:50, 0:100) to
give 5 fractions (Frs. 9-3-3-1 ꢃ 9-3-3-5). Fr. 9-3-3-4 (169.2 mg) was purified by semi-pre-
parative reversed-phase HPLC (2 mL/min, CH CN/H O ¼ 15:85) to obtain 6 (1.6 mg, t
3
2
R

NATURAL PRODUCT RESEARCH
5
¼
28.3 min). Fr. 10 (9.5 g) was applied to silica gel column (U 60 mm ꢂ 800 mm) eluted
with CH Cl /CH OH (100:0, 99:1, 98:2, 97:3, 96:4, 95:5, 93:7, 90:10, 80:20, 70:30, 50:50,
2
2
3
0
:100) to gain 9 fractions (Frs. 10-1 ꢃ 10-9). Fr. 10-4 (1.6 g) was subjected to silica gel
column (U 40 mm ꢂ 500 mm) eluted with CH Cl /acetone (100:0, 99:1, 98:2, 97:3, 96:4,
2
2
9
1
5:5, 93:7, 90:10, 80:20, 70:30, 50:50, 0:100) to gain 4 fractions (Frs. 10-4-1 ꢃ 10-4-4). Fr.
0-4-4 (592.8 mg) was isolated by semi-reparative reversed-phase HPLC (2 mL/min,
CH OH/H O ¼ 20:80) to give 10 (9.7 mg, t ¼ 28.6 min).
3
2
R
2
D
5
Baeriamide (1): white powders; ½aꢄ ꢁ22.2 (c 0.3, CH CH OH); HR-ESI-MS: m/z
3
2
þ
2
67.1310 [M þ Na] (calcd for C H N O Na: 267.1315); UV (CH CN) k : 191 nm; IR
11
20
2
4
3
max
ꢁ1 1 13
(KBr) ꢀmax: 3280, 2961, 2975, 2852, 1731, 1651, 1439 and 1385 cm ; H and C NMR
data see Table S1.
3.4. Marfey’s analysis of 1
ꢅ
A solution of 1 (0.3 mg) in 6 N (HCl) was heated at 110 C for 16 h. After removing the
excess HCl under vacuum, the dry hydrolysate was dissolved in pure water (50 lL) and
treated with 1% solution of FDLA (100 mL) in acetone followed by 1.0 M NaHCO3
ꢅ
(
20 mL). The reaction mixture was heated at 43 C under ultrasonication for 1 h and
cooled. Then 20 lL of 1 N HCl was added. The solution of derivative was evaporated
to dryness and dissolved in 300 lL MeOH. Likewise, authentic D- and L-valine were
derivatised separately. The derivatised hydrolysate of 1 and standard amino acids
were applied to HPLC-HRMS using the following gradient program. Solvent A: H O
2
(0.1% HCOOH). Solvent B: acetonitrile. Linear gradient, 30% to 70% of B in 50 min,
flow rate 1 mL/min. The retention time of FDLA derivatives of the hydrolysate of 1 and
standard L- and D-valine were observed at 21.6, 21.6 and 30.6 min, respectively.
4. Conclusions
The chemical investigation of the marine sponge H. baeri led to the isolation of a new
amide (1) and nine known diketopiperazines (2-10). Compound 1 was derived from
dehydration of formylated L-valine with c-amino-butanoic acid methyl ester.
Compounds 2-10 were isolated from the sponge of genus Haliclona for the first time.
The absolute confirmation of 7 was confirmed firstly by the means of single-crystal X-
ray diffraction. The cytotoxic, antibacterial, antiviral and antifouling activities of these
compounds were also tested. However, Compounds 1-10 exhibited no significant
activities. Therefore, the biological activities of 1-10 will be further explored such as
the neuro differentiation, cytotoxic against other cell lines and antifungal activities.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was financially supported by the National Key Research and Development Plan of
China [grant Nos. 2019YFD0901905 and 2018YFC0310900]; the National Natural Science

6
Y.-F. XIAO ET AL.
Foundation of China [grant Nos. 41876145, 81874292 and 21672084]; the Science and
Technology Planning Project of Guangzhou (grant Nos. 202102010066 and 201704030042); the
Key Program of Marine Economy Development (Six Marine Industries) Special Foundation of
Department of Natural Resources of Guangdong Province (grant No. [2020]037).
References
Arai M, Ishida S, Setiawan A, Kobayashi M. 2009. Haliclonacyclamines, tetracyclic alkylpiperidine
alkaloids, as anti-dormant mycobacterial substances from a marine sponge of Haliclona sp.
Chem Pharm Bull (Tokyo). 57(10):1136–1138.
Ayyad SEN, Bahaffi SOS, Hashish NE. 2009. Isolation and structure determination of the biologic-
ally active sphingolipids from marine sponge Haliclona species. Nat Prod Res. 23(1):44–50.
Bach B, Gregson RP, Holland GS, Quinn RJ, Reichelt JL. 1978. L-Azetidine-2-carboxylic acid, the
antidermatophyte constituent of two marine sponges. Cell Mol Life Sci. 34(6):688–688.
Casapullo A, Pinto OC, Marzocco S, Autore G, Riccio R. 2009. 3-Alkylpyridinium alkaloids from
the Pacific sponge Haliclona sp. J Nat Prod. 72(2):301–303.
Chen M, Wu XD, Shen NX, Wang CY. 2017. Four new 6-oxy purine alkaloids from the South
China Sea sponge Haliclona cymaeformis. J Ocean Univ China. 16(6):1183–1186.
Defant A, Mancini I, Raspor L, Guella G, Turk T, Sep ꢀc i ꢁc K. 2011. New structural insights into sar-
aines A, B, and C, macrocyclic alkaloids from the Mediterranean sponge Reniera (Haliclona)
sarai. Eur J Org Chem. 20-21:3761–3767.
€
Einarsdottir E, Magnusdottir M, Astarita G, K o€ ck M, Ogmundsdottir H, Thorsteinsdottir M, Rapp
H, Omarsdottir S, Paglia G. 2017. Metabolic profiling as a screening tool for cytotoxic com-
pounds: identification of 3-alkyl pyridine alkaloids from sponges collected at a shallow water
hydrothermal vent site north of Iceland. Mar Drugs. 15(2):52.
Furtado NAJC, Pupo MT, Carvalho I, Campo VL, Duarte MCT, Bastos JK. 2005. Diketopiperazines
produced by an Aspergillus fumigatus Brazilian strain. J Braz Chem Soc. 16(6B):1448–1453.
Genta-Jouve G, Thomas OP. 2013. Absolute configuration of the new 3-epi-cladocroic acid from
the mediterranean sponge Haliclona fulva. Metabolites. 3(1):24–32.
Jayatilake GS, Thornton MP, Leonard AC, Grimwade JE, Baker BJ. 1996. Metabolites from an
Antarctic sponge-associated bacterium, Pseudomonas aeruginosa. J Nat Prod. 59(3):293–296.
Khedr AIM, Kouno I, Tanaka T, Yamada K. 2013. New diketopiperazine derivatives from culture
broth of Staphylococcus sp. isolated from Corallina officinalis Lineaus. Heterocycles. 87(5):
1029–1037.
K o€ ck M, Mu n~ oz J, Cychon C, Timm C, Schmidt G. 2013. The arctic sponge Haliclona viscosa as a
source of a wide array of 3-alkyl pyridine alkaloids. Phytochem Rev. 12(3):391–406.
Kong CJ, Li L, Chen M, Cao F, Wang CY. 2016. Brominated polyunsaturated lipids and steroids
from the South China Sea sponge Haliclona subarmigera. Chem Nat Compd. 52(5):883–885.
Li B, Chen G, Bai J, Jing YK, Pei YH. 2011. A bisamide and four diketopiperazines from a marine-
derived Streptomyces sp. J Asian Nat Prod Res. 13(12):1146–1150.
Li T, Wang G, Huang X, Ye W. 2013. Whitmanoside A, a new a-pyrone glycoside from the leech
Whitmania pigra. Heterocycles. 87(7):1537–1543.
Liang YQ, Liao XJ, Lin JL, Xu W, Chen GD, Zhao BX, Xu SH. 2019. Spongiains a-c: three new
spongian diterpenes with ring a rearrangement from the marine sponge Spongia sp.
Tetrahedron. 75(27):3802–3808.
Liang YQ, Liao XJ, Zhao BX, Xu SH. 2019. (þ)- and (-)-Spongiterpene, a pair of new valerenane
sesquiterpene enantiomers from the marine sponge Spongia sp. Nat Prod Res. :1–6.doi:10.
1080/14786419.2019.1666384.
Liang YQ, Liao XJ, Zhao BX, Xu SH. 2020. Novel 3,4-seco-3,19-dinorspongian and 5,17-epoxy-19-
norspongian diterpenes from the marine sponge Spongia sp. Org Chem Front. 7(20):3253–3261.
Marfey P. 1984. Determination of D-amino acids. II. Use of a bifunctional reagent, 1,5-difluoro-
2,4-dinitrobenzene. Carlsberg Res Commun. 49(6):591–596.

NATURAL PRODUCT RESEARCH
7
Nuzzo G, Ciavatta ML, Villani G, Manzo E, Zanfardino A, Varcamonti M, Gavagnin M. 2012.
Fulvynes, antimicrobial polyoxygenated acetylenes from the Mediterranean sponge Haliclona
fulva. Tetrahedron. 68(2):754–760.
Park YC, Gunasekera SP, Lopez JV, McCarthy PJ, Wright AE. 2006. Metabolites from the marine-
derived fungus Chromocleista sp. isolated from a deep-water sediment sample collected in
the Gulf of Mexico. J Nat Prod. 69(4):580–584.
Pedras MSC, Yu Y, Liu J, Tandron-Moya YA. 2005. Metabolites produced by the phytopathogenic
fungus Rhizoctonia solani: isolation, chemical structure determination, syntheses and bioactiv-
ity. Z Naturforsch C J Biosci. 60(9-10):717–722.
Randazzo A, Bifulco G, Giannini C, Bucci M, Debitus C, Cirino G, Gomez-Paloma L. 2001.
Halipeptins A and B: two novel potent anti-inflammatory cyclic depsipeptides from the
Vanuatu marine sponge Haliclona species. J Am Chem Soc. 123(44):10870–10876.
Ranjalahy-Rasoloarijao L, Lazaro R, Daumas P, Heitz F. 1989. Synthesis and ionic channels of a
linear gramicidin containing naphthylalanine instead of tryptophan. Int J Pept Protein Res.
33(4):273–280.
Rashid MA, Gustafson KR, Boswell JL, Boyd MR. 2000. Haligramides A and B, two new cytotoxic
hexapeptides from the marine sponge Haliclona nigra. J. Nat. Prod. 63(7):956–959.
Reyes F, Fern ꢁa ndez R, Urda C, Francesch A, Bueno S, de Eguilior C, Cuevas C. 2007. Njaoamines
A–F, new cytotoxic polycyclic alkaloids from the haplosclerid sponge Reniera sp. Tetrahedron.
63(11):2432–2438.
Sera Y, Adachi K, Fujii K, Shizuri Y. 2003. A new antifouling hexapeptide from a Palauan sponge,
Haliclona sp. J Nat Prod. 66(5):719–721.
Ukwueze SE, Osadebe PO, Okoye FB. 2015. A new antibacterial benzophenone glycoside from
Psidium guajava (Linn.) leaves. Nat Prod Res. 29(18):1728–1734.
Wang B, Dong J, Zhou X, Lee KJ, Huang R, Zhang S, Liu Y. 2009. Nucleosides from the marine
sponge Haliclona sp. Z Naturforsch C J Biosci. 64(1-2):143–148.
Wang B, Lee KJ, Zhang S, Jung JH, Liu Y. 2009. 2-Palmitamidoethanesulfonic acid, a taurine
derivative from the marine sponge Haliclona sp. Chem Nat Compd. 45(1):137–138.
Wang GH, Dai SK, Chen MJ, Wu HB, Xie LW, Luo XM, Li X. 2010. Two diketopiperazine cyclo (pro-
phe) isomers from marine bacteria Bacillus subtilis sp. 13-2. Chem Nat Compd. 46(4):583–585.
Wang J, Su P, Gu Q, Li WD, Guo JL, Qiao W, Feng DQ, Tang SA. 2017. Antifouling activity against
bryozoan and barnacle by membrane diterpenes from the soft coral Sinularia flexibilis. Int
Biodeter Biodegr. 120:97–103.
Wattanadilok R, Sawangwong P, Rodrigues C, Cidade H, Pinto M, Pinto E, Silva A, Kijjoa A. 2007.
Antifungal activity evaluation of the constituents of Haliclona baeri and Haliclona cymaeformis,
collected from the Gulf of Thailand. Mar Drugs. 5(2):40–51.
Wu Z-N, Chen N-H, Tang Q, Chen S, Zhan Z-C, Zhang Y-B, Wang G-C, Li Y-L, Ye W-C. 2020. b-car-
boline alkaloids from the seeds of peganum harmala and their anti-hsv-2 virus activities. Org
Lett. 22(18):7310–7314.
Xie CL, Niu SW, Xia JM, Peng K, Zhang GY, Yang XW. 2018. Saccharopolytide A, a new cyclic tet-
rapeptide with rare 4-hydroxy-proline moieties from the deep-sea derived actinomycete
Saccharopolyspora cebuensis MCCC 1A09850. Nat Prod Res. 32(14):1627–1631.
Yang B, Huang JX, Lin XP, Zhang YY, Tao HM, Liu YH. 2016. A new diketopiperazine from the
marine sponge Callyspongia species. Rec Nat Prod. 10(1):117–121.
Yonezawa K, Yamada K, Kouno I. 2011. New diketopiperazine derivatives isolated from sea
urchin-derived Bacillus sp. Chem Pharm Bull (Tokyo). 59(1):106–108.
Zhang H, Lai W, Guan ZB, Liao XJ, Zhao BX, Xu SH. 2020. A new thiodiketopiperzaine from the
marine sponge Tedania sp. Nat Prod Res. 34(8):1113–1117.
Zhu JY, Liu Y, Liu ZJ, Wang H, Zhang HW. 2019. Bioactive nitrogenous secondary metabolites
from the marine sponge genus Haliclona. Mar Drugs. 17(12):682.