Abstract
Marine bis-indole alkaloids comprise a large and increasingly growing class of secondary metabolites, and continue to deliver a great variety of structural templates for diverse biological targets. The alkaloids derived from marine resources play a crucial role in medicinal chemistry and as chemical agents. In particular, bis-indole alkaloid caulerpin which has been isolated from marine green algae Caulerpa and a red algae Chondria armata at various places around the world, was tested for several therapeutic potentials such as anti-diabetic, antinociceptive, anti-inflammatory, anti-tumor, anti- larvicidal, anti-herpes, anti-tubercular, anti-microbial and immunostimulating activities as well as a means of other chemical agents. Herein, we summarized the discovery and isolation of caulerpin, and its potential medicinal and chemical applications in chronological order with various aspects. Additionally, synthesis of caulerpin and its functional analogues have also been reviewed.
Keywords: Bis-indole alkaloid, caulerpin, biological activity, marine natural product, total synthesis, secondary metabolites.
Graphical Abstract
[1]
Molinski, T.F.; Dalisay, D.S.; Lievens, S.L.; Saludes, J.P. Drug development from marine natural products. Nat. Rev. Drug Discov., 2009, 8, 69-85.
[2]
Haefner, B. Drugs from the deep: Marine natural products as drug candidates. Drug Discov. Today, 2003, 8(12), 536-544.
[3]
Simmons, T.L.; Andrianasolo, E.; McPhail, K.; Flatt, P.; Gerwick, W.H. Marine natural products as anticancer drugs. Mol. Cancer Ther., 2005, 4(2), 333-342.
[5]
Koehn, F.E.; Carter, G.T. The evolving role of natural products in drug discovery. Nat. Rev. Drug Discov., 2004, 4, 206-220.
[6]
Mayer, A.M.; Glaser, K.B.; Cuevas, C.; Jacobs, R.S.; Kem, W.; Little, R.D.; McIntosh, J.M.; Newman, D.J.; Potts, B.C.; Shuster, D.E. The odyssey of marine pharmaceuticals: A current pipeline perspective. Trends Pharmacol. Sci., 2010, 31(6), 255-265.
[7]
Krause, J.; Tobin, G. Discovery; Development, and Regulation of Natural Products, InTech, 2013.
[http://dx.doi.org/10.5772/56424]
[http://dx.doi.org/10.5772/56424]
[8]
Williams, D.H.; Stone, M.J.; Hauck, P.R.; Rahman, S.K. Why are secondary metabolites (natural products) biosynthesized? J. Nat. Prod., 1989, 52, 1189-1208.
[9]
Firn, R.D.; Jones, C.G. Natural products: A simple model to explain chemical diversity. Nat. Prod. Rep., 2003, 20, 382-391.
[11]
Hu, G.P.; Yuan, J.; Sun, L.; She, Z.G.; Wu, J.H.; Lan, X.J.; Zhu, X.; Lin, Y.C.; Chen, S.P. Statistical research on marine natural products based on data obtained between 1985 and 2008. Mar. Drugs, 2011, 9, 514-525.
[12]
Gul, W.; Hamann, M.T. Indole alkaloid marine natural products: An established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases. Life Sci., 2005, 78, 442-453.
[13]
França, P.H.B.; Barbosa, D.P.; da Silva, D.L.; Ribeiro, Ê.A.N.; Santana, A.E.G.; Santos, B.V.O.; Barbosa-Filho, J.M.; Quintans, J.S.S.; Barreto, R.S.S.; Quintans-Júnior, L.J.; de Araújo-Júnior, J.X. Indole alkaloids from marine sources as potential leads against
infectious diseases BioMed. Res. Int, 2014, 2014
[15]
Kochanowska-Karamyan, A.J.; Hamann, M.T. Marine indole alkaloids: potential new drug leads for the control of depression and anxiety. Chem. Rev., 2010, 110, 4489-4497.
[16]
Williams, J.E. Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on uña de gato and sangre de grado. Altern. Med. Rev., 2001, 6, 567-579.
[17]
Liu, D-Q.; Mao, S-C.; Zhang, H-Y.; Yu, X-Q.; Feng, M-T.; Wang, B.; Feng, L-H.; Guo, Y-W. Racemosins A and B, two novel bisindole alkaloids from the green alga Caulerpa racemosa. Fitoterapia, 2013, 91, 15-20.
[18]
aKnolker, H-J.; Reddy, K.R. Isolation and synthesis of biologically active carbazole alkaloids. Chem. Rev., 2002, 102, 4303-4427.
bHibino, S.; Choshi, T. Simple indole alkaloids and those with a nonrearranged monoterpenoid unit. Nat. Prod. Rep., 2001, 18, 66-87.
cNishizawa, Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature, 1984, 308, 693-698.
dNishizawa, Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature, 1988, 334, 661-665.
eNishizawa, Y. Studies and perspectives of protein kinase C. Science, 1986, 233, 305-312.
fStewart, A.F.; Schultz, G. Camptothecin-induced in vivo topoisomerase I cleavages in the transcriptionally active tyrosine aminotransferase gene. Cell, 1987, 50, 1109-1117.
gMerino, A.; Madden, K.R.; Lane, W.S.; Champoux, D. DNA topoisomerase I is involved in both repression and activation of transcription. Nature, 1993, 365, 227-232.
bHibino, S.; Choshi, T. Simple indole alkaloids and those with a nonrearranged monoterpenoid unit. Nat. Prod. Rep., 2001, 18, 66-87.
cNishizawa, Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature, 1984, 308, 693-698.
dNishizawa, Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature, 1988, 334, 661-665.
eNishizawa, Y. Studies and perspectives of protein kinase C. Science, 1986, 233, 305-312.
fStewart, A.F.; Schultz, G. Camptothecin-induced in vivo topoisomerase I cleavages in the transcriptionally active tyrosine aminotransferase gene. Cell, 1987, 50, 1109-1117.
gMerino, A.; Madden, K.R.; Lane, W.S.; Champoux, D. DNA topoisomerase I is involved in both repression and activation of transcription. Nature, 1993, 365, 227-232.
[19]
Rubnov, S.; Chevallier, C.; Thoison, O.; Debitus, C.; Laprevote, O.; Guénard, D.; Sévenet, T. Echinosulfonic acid D: An ESI MSn evaluation of a new cytotoxic alkaloid from the New-Caledonian sponge Psammoclemma sp. Nat. Prod. Res., 2005, 19, 75-79.
[20]
Reyes, F.; Fernández, R.; Rodríguez, A.; Bueno, S.; de Eguilior, C.; Francesch, A.; Cuevas, C. Cytotoxic staurosporines from the marine ascidian Cystodytes solitus. J. Nat. Prod., 2008, 71, 1046-1048.
[21]
Jimenez, P.C.; Wilke, D.V.; Ferreira, E.G.; Takeara, R.; de Moraes, M.O.; Silveira, E.R.; da Cruz Lotufo, T.M.; Lopes, N.P.; Costa-Lotufo, L.V. Structure elucidation and anticancer activity of 7-oxostaurosporine derivatives from the Brazilian endemic tunicate Eudistoma vannamei. Mar. Drugs, 2012, 10, 1092-1102.
[22]
aKobayashi, J.; Murayama, T.; Ishibashi, M.; Kosuge, S.; Takamatsu, M.; Ohizumi, Y.; Kobayashi, H.; Ohta, T.; Nozoe, S.; Sasaki, T. Hyrtiosins A and B, new indole alkaloids from the Okinawan marine sponge Hyrtios erecta. Tetrahedron, 1990, 46, 7699-7702.
bBergman, J.; Venemalm, L. Synthesis of cyclopent[b]indolones. Tetrahedron, 1990, 46, 6061-6066.
bBergman, J.; Venemalm, L. Synthesis of cyclopent[b]indolones. Tetrahedron, 1990, 46, 6061-6066.
[23]
aBartik, K.; Braekman, J-C.; Daloze, D.; Stoller, C.; Huysecom, J.; Vandevyer, G.; Ottinger, R. Topsentins, new toxic bis-indole alkaloids from the marine sponge Topsentiagenitrix. Can. J. Chem., 1987, 65, 2118-2121.
bTsuji, S.; Rinehart, K.L.; Gunasekera, S.P.; Kashman, Y.; Cross, S.S.; Lui, M.S.; Pomponi, S.A.; Diaz, M.C. Topsentin, Bromotopsentin, and Dihydrodeoxybromotopsentin: Antiviral and Antitumor bis (indolyl)imidazoles from Caribbean deep-sea sponge of the family Halichondriidae. Structural and synthetic studies. J. Org. Chem., 1988, 53, 5446-5453.
cMorris, S.A.; Andersen, R.J. Nitrogenous metabolites from the deep water sponge Hexadella sp. Can. J. Chem., 1989, 67, 677-681.
dMurray, L.M.; Lim, T.K.; Hooper, J.N.A.; Capon, R.J. Isobromotopsentin: a new bis(indo1e) alkaloid from a deep-water marine sponge Spongosorites sp. Aust. J. Chem., 1995, 48, 2053-2058.
eShin, J.; Seo, Y.; Cho, K.W.; Rho, J-R.; Sim, C.J. New bis(indole)alkaloids of the topsentin class from the sponge Spongosorites genitrix. J. Nat. Prod., 1999, 62, 647-649.
bTsuji, S.; Rinehart, K.L.; Gunasekera, S.P.; Kashman, Y.; Cross, S.S.; Lui, M.S.; Pomponi, S.A.; Diaz, M.C. Topsentin, Bromotopsentin, and Dihydrodeoxybromotopsentin: Antiviral and Antitumor bis (indolyl)imidazoles from Caribbean deep-sea sponge of the family Halichondriidae. Structural and synthetic studies. J. Org. Chem., 1988, 53, 5446-5453.
cMorris, S.A.; Andersen, R.J. Nitrogenous metabolites from the deep water sponge Hexadella sp. Can. J. Chem., 1989, 67, 677-681.
dMurray, L.M.; Lim, T.K.; Hooper, J.N.A.; Capon, R.J. Isobromotopsentin: a new bis(indo1e) alkaloid from a deep-water marine sponge Spongosorites sp. Aust. J. Chem., 1995, 48, 2053-2058.
eShin, J.; Seo, Y.; Cho, K.W.; Rho, J-R.; Sim, C.J. New bis(indole)alkaloids of the topsentin class from the sponge Spongosorites genitrix. J. Nat. Prod., 1999, 62, 647-649.
[24]
aBonjouklian, R.; Smitka, T.A.; Doolin, L.E.; Molloy, R.M.; Debono, M.; Shaffer, S.A.; Moore, R.E.; Stewart, J.B.; Patterson, G.M.L. Tjipanazoles, new antifungal agents from the blue-green alga Tolypothrix tjipanasensis. Tetrahedron, 1991, 47, 7739-7750.
bKuethe, J.T.; Wong, A.; Davies, I.W. Effective strategy for the preparation of indolocarbazole aglycons and glycosides: Total synthesis of tjipanazoles B, D, E, and I. Org. Lett., 2003, 5, 3721-3723.
cGilbert, E.J.; Ziller, J.W.; Van Vranken, D.L. Cyclizations of unsymmetrical bis-1,2-(3-indolyl)ethanes: Synthesis of (−)-tjipanazole F1. Tetrahedron, 1997, 53, 16553-16564.
bKuethe, J.T.; Wong, A.; Davies, I.W. Effective strategy for the preparation of indolocarbazole aglycons and glycosides: Total synthesis of tjipanazoles B, D, E, and I. Org. Lett., 2003, 5, 3721-3723.
cGilbert, E.J.; Ziller, J.W.; Van Vranken, D.L. Cyclizations of unsymmetrical bis-1,2-(3-indolyl)ethanes: Synthesis of (−)-tjipanazole F1. Tetrahedron, 1997, 53, 16553-16564.
[25]
aSu, J-Y.; Zhu, Y.; Zeng, L-M.; Xu, X-H. A new bisindole from alga Caulerpa serrulata. J. Nat. Prod., 1997, 60, 1043-1044.
bWahlstrom, N.; Stensland, B.; Bergman, J. Synthesis of the marine alkaloid caulersin. Tetrahedron, 2004, 60, 2147-2153.
cBourderioux, A.; Routier, S.; Beneteau, V.; Merour, J-Y. Synthesis of benzo analogues of oxoarcyriaflavins and caulersine. Tetrahedron, 2007, 63, 9465-9475.
dMiki, Y.; Aoki, Y.; Miyatake, H.; Minematsu, T.; Hibino, H. Synthesis of caulersin and its isomers by reaction of indole-2,3-dicarboxylic anhydrides with methyl indoleacetates. Tetrahedron Lett., 2006, 47, 5215-5218.
bWahlstrom, N.; Stensland, B.; Bergman, J. Synthesis of the marine alkaloid caulersin. Tetrahedron, 2004, 60, 2147-2153.
cBourderioux, A.; Routier, S.; Beneteau, V.; Merour, J-Y. Synthesis of benzo analogues of oxoarcyriaflavins and caulersine. Tetrahedron, 2007, 63, 9465-9475.
dMiki, Y.; Aoki, Y.; Miyatake, H.; Minematsu, T.; Hibino, H. Synthesis of caulersin and its isomers by reaction of indole-2,3-dicarboxylic anhydrides with methyl indoleacetates. Tetrahedron Lett., 2006, 47, 5215-5218.
[26]
Aguilar-Santos, G. Caulerpin, a new red pigment from green algae of the genus Caulerpa. J. Chem. Soc., 1970, 6, 842-843. [C].
[27]
Aguilar-Santos, G. Doty. M.S. in Drugs from the sea (1968)
(Freudenthal, H.D., ed.) p. 173 Marin Technology Society, Washington,
DC
[28]
Dumay, O.; Fernandez, C.; Pergent, G. Primary production and vegetative cycle in Posidonia oceanica when in competition with the green algae Caulerpa taxifolia and Caulerpa racemosa. J. Mar. Biol. Assoc. U. K., 2002, 82, 379-387.
[29]
Capon, R.J.; Ghisalberti, E.L.; Jefferies, P.R. Metabolites of the green algae, Caulerpa Species. Phytochemistry, 1983, 22(6), 1465-1467.
[30]
Vest, S.E.; Dawes, C.J.; Romeo, J.T. Distribution of caulerpin and caulerpicin in eight species of the green alga Caulerpa (Caulerpales). Bot. Mar., 1983, XXVI, 313-316.
[31]
Schwede, J.G.; Cardellina, J.H.; Grode, S.H.; James, Jr, T.R.; Blackman, A.J. Distribution of the pigment caulerpin in species of the green alga Caulerpa. Phytochemistry, 1987, 26(1), 155-158.
[32]
Raub, M.F.; Cardellina, J.H.; Schwede, J.G. The green algal pigment caulerpin as a plant growth regulator. Phytochemistry, 1987, 26, 619-620.
[33]
Anjaneyulu, A.S.R.; Prakash, C.V.S.; Mallavadhani, U.V. Two caulerpin analogues and a sesquiterpene from Caulerpa racemosa. Phytochemistry, 1991, 30(9), 3041-3042.
[34]
Govenkar, M.B.; Wahidulla, S. Constituents of Chondria armata. Phytochemistry, 2000, 54, 979-981.
[35]
Vottero, E.; Balgi, A.; Woods, K.; Tugendreich, S.; Melese, T.; Andersen, R.J.; Grant Mauk, A.; Roberge, M. Inhibitors of human indoleamine 2,3-dioxygenase identified with a target-based screen in yeast. Biotechnol. J., 2006, 1, 282-288.
[36]
Mao, S-C.; Guo, Y-W.; Shen, X. Two novel aromatic valerenane-type sesquiterpenes from the Chinese green alga Caulerpa taxifolia. Bioorg. Med. Chem. Lett., 2006, 16, 2947-2950.
[37]
Rocha, F.D.; Soares, A.R.; Houghton, P.J.; Pereira, R.C.; Kaplan, M.A.C.; Teixeira, V.L. Potential cytotoxic activity of some Brazilian seaweeds on human melanoma cells. Phytother. Res., 2007, 21, 170-175.
[38]
de Souza, É.T.; de Lira, D.P.; de Queiroz, A.C.; da Silva, D.J.C.; de Aquino, A.B.; Campessato Mella, E.A.; Lorenzo, V.P.; de Miranda, G.E.C.; de Araújo-Júnior, J.X.; de Oliveira Chaves, M.C.; Barbosa-Filho, J.M.; de Athayde-Filho, P.F.; de Oliveira Santos, B.V.; Alexandre-Moreira, M.S. The antinociceptive and anti-inflammatory activities of caulerpin, a bisindole alkaloid isolated from seaweeds of the genus Caulerpa. Mar. Drugs, 2009, 7, 689-704.
[39]
Alarif, W.M.; Abou-Elnaga, Z.S.; Ayyad, S-E.N.; Al-lihaibi, S.S. Insecticidal metabolites from the green alga Caulerpa racemosa. Clean Soil, Air. Water, 2010, 38(5-6), 548-557.
[40]
Kamal, C.; Sethuraman, M.G. Caulerpin-a bis-indole alkaloid as a green inhibitor for the corrosion of mild steel in 1 M HCl solution from the marine alga Caulerpa racemosa. Ind. Eng. Chem. Res., 2012, 51, 10399-10407.
[41]
Macedo, N.R.P.V.; Ribeiro, M.S.; Villaça, R.C.; Ferreira, W.; Pinto, A.M.; Teixeira, V.L.; Cirne-Santos, C.; Paixão, I.C.N.P.; Giongo, V. Caulerpin as a potential antiviral drug against herpes simplex virus type 1. Rev. Bras. Farmacogn., 2012, 22(4)
[42]
Pinto, A.M.V.; Leite, J.P.G.; Ferreira, W.J.; Cavalcanti, D.N.; Villaça, R.C.; Giongo, V.; Teixeira, V.L.; de Palmer Paixão, I.C.N. Marine natural seaweed products as potential antiviral drugs against Bovine viral diarrhea virus. Rev. Bras. Farmacogn., 2012, 22(4)
[43]
Cavalcante-Silva, L.H.A.; de Carvalho Correia, A.C.; Barbosa-Filho, J.M.; da Silva, B.A.; de Oliveira Santos, B.V.; de Lira, D.P.; Sousa, J.C.F.; de Miranda, G.E.C.; de Andrade Cavalcante, F.; Alexandre-Moreira, M.S. Spasmolytic effect of caulerpine involves blockade of Ca2+ influx on guinea pig ileum. Mar. Drugs, 2013, 11, 1553-1564.
[44]
Nagappan, T.; Vairappan, C.S. Nutritional and bioactive properties of three edible species of green algae, genus Caulerpa (Caulerpaceae). J. Appl. Phycol., 2014, 26, 1019-1027.
[45]
Maiti, B.C.; Thomson, R.H.; Mahendran, M.J. The structure of caulerpin, a pigment from Caulerpa algae. Chem. Res. Synop, 1978, 4, 126-127.
[46]
Canché Chay, C.I.; Cansino, R.G.; Espitia Pinzón, C.I.; Torres-Ochoa, R.O.; Martínez, R. Synthesis and anti-tuberculosis activity of the marine natural product caulerpin and its analogues. Mar. Drugs, 2014, 12, 1757-1772.
[47]
Talaz, O.; Saracoglu, N. A study on the synthesis of structural analogues of bis-indole alkaloid caulerpin: A step-by-step synthesis of a cyclic indole-tetramer. Tetrahedron, 2010, 66, 1902-1910.
[48]
Vidal, J.P.; Laurent, D.; Kabore, S.A.; Rechencq, E.; Boucard, M.; Girard, J.P.; Escale, R.; Rossi, J.C. Caulerpin, caulerpicin, Caulerpa scalpelliformis: comparative acute toxicity study. Bot. Mar., 1984, XXVII, 533-537.
[49]
Schwede, J.G. Process for promoting and regulating plant growth
with caulerpin. U.S. Patent 4,608,077, August 26. 1986.
[50]
Liu, L.; Pohnert, G.; Wei, D. Extracellular metabolites from industrial microalgae and their biotechnological potential. Mar. Drugs, 2016, 14, 191.
[51]
Saltiel, A.R.; Kahn, C.R. Insulin signaling and the regulation of glucose and lipid metabolism. Nature, 2001, 414, 799-806.
[52]
Obici, S.; Feng, Z.; Karkanias, G.; Baskin, D.G.; Rossetti, L. Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat. Neurosci., 2002, 5, 566-572.
[53]
Saltiel, A.R.; Pessin, J.E. Insulin signaling pathways in time and space. Trends Cell Biol., 2002, 12, 65-71.
[54]
Bryant, N.J.; Govers, R.; James, D.E. Regulated transport of the glucose transporter GLUT4. Nat. Rev. Mol. Cell Biol., 2002, 3, 267-277.
[55]
Smith, U. Impaired (‘diabetic’) insulin signaling and action occur in fat cells long before glucose intolerance — is insulin resistance initiated in the adipose tissue? Int. J. Obes. Relat. Metab. Disord., 2002, 26, 897-904.
[56]
Ostman, A.; Bohmer, F.D. Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatases. Trends Cell Biol., 2001, 11, 258-266.
[57]
Cheng, A.; Dube, N.; Gu, F.; Tremblay, M.L. Coordinated action of protein tyrosine phosphatases in insulin signal transduction. Eur. J. Biochem., 2002, 269, 1050-1059.
[58]
Goldstein, B.J.; Bittner-Kowalczyk, A.; White, M.F.; Harbeck, M. Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the GRB2 adaptor protein. J. Biol. Chem., 2000, 275, 4283-4289.
[59]
Johnson, T.O.; Ermolieff, J.; Jirousek, M.R. Protein tyrosine phosphatase 1b inhibitors for diabetes. Nat. Rev. Drug Discov., 2002, 1, 696-709.
[60]
Cavalcante-Silva, L.H.A.; Falcão, M.A.P.; Vieira, A.C.S.; Viana, M.D.M.; de Araújo-Júnior, J.X.; Sousa, J.C.F.; da Silva, T.M.S.; Barbosa-Filho, J.M.; Noël, F.; de Miranda, G.E.C.; de Oliveira Santos, B.V.; Alexandre-Moreira, M.S. Assessment of mechanisms involved in antinociception produced by the alkaloid caulerpine. Molecules, 2014, 19, 14699-14709.
[61]
Liu, Y.; Morgan, J.B.; Coothankandaswamy, V.; Liu, R.; Jekabsons, M.B.; Mahdi, F.; Nagle, D.G.; Zhou, Y-D. The Caulerpa pigment caulerpin inhibits HIF-1 activation and mitochondrial respiration. J. Nat. Prod., 2009, 72, 2104-2109.
[62]
Yu, H.; Zhang, H. Dong. M.; Wu. Z.; Shen. Z.; Xie, Y.; Kong, Z.; Dai, X.; Xu, B. Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells. Int. J. Oncol., 2017, 50, 161-172.
[63]
El-Bahnasawy, M.M.; Fadil, E.E.; Morsy, T.A. Mosquito vectors of infectious diseases: are they neglected health disaster in Egypt? J. Egypt. Soc. Parasitol., 2013, 43(2), 373-386.
[64]
Arduino, P.G.; Porter, S.R. Oral and perioral herpes simplex virus type 1 (HSV-1) infection: Review of its management. Oral Dis., 2006, 12, 254-270.
[65]
World Health Organization. Global Tuberculosis report 2016.
WHO Press, World Health Organization, Geneva. 2016, ISBN:
978-92-4-156539-4.
[66]
Kumar, V.; Abbas, A.K.; Fausto, N.; Mitchell, R.N. Robbins Basic
Pathology, 8th ed.; Saunders Elsevier: 2007, 516-522. ISBN 978-1- 4160-2973-1.
[68]
Zumla, A.; Raviglione, M.; Hafner, R.; von Reyn, C.F. Tuberculosis. N. Engl. J. Med., 2013, 368(8), 745-755.
[69]
Moloney, M.G. Natural products as a source for novel antibiotics. Trends Pharmacol. Sci., 2016, 37(8), 689-701.
[70]
Chan, G.J.; Lee, A.C.; Baqui, A.H.; Tan, J.; Black, R.E. Risk of early-onset neonatal infection with maternal infection or colonization: A global systematic review and meta-analysis. PLoS Med., 2013, 10(8), e1001502.
[71]
Kumar, M.; Kumari, P.; Trivedi, N.; Shukla, M.K.; Gupta, V.; Reddy, C.R.K.; Jha, B. Minerals, PUFAs and antioxidant properties of some tropical seaweeds from Saurashtra coast of India. J. Appl. Phycol., 2011, 23, 797-810.
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