Comparative Biochemistry and Physiology, Part C 145 (2007) 553–581 www.elsevier.com/locate/cbpc Marine pharmacology in 2003–4: Marine compounds with anthelmintic antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems, and other miscellaneous mechanisms of action ⁎ Alejandro M.S. Mayer a, , Abimael D. Rodríguez b, Roberto G.S. Berlinck c, Mark T. Hamann d a Department of Pharmacology, Chicago College of Osteopathic Medicine, Midwestern University, 555 31st Street, Downers Grove, Illinois 60515, USA b Department of Chemistry, University of Puerto Rico, San Juan, Puerto Rico 00931, USA c Instituto de Quimica de Sao Carlos, Universidade de Sao Paulo, Sao Carlos, 13560-970, Brazil d School of Pharmacy, The University of Mississippi, Faser Hall, University, Mississippi 38677, USA Received 28 October 2006; received in revised form 29 January 2007; accepted 30 January 2007 Available online 9 February 2007 Abstract The current marine pharmacology review that covers the peer-reviewed literature during 2003 and 2004 is a sequel to the authors' 1998–2002 reviews, and highlights the preclinical pharmacology of 166 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria. Anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 67 marine chemicals. Additionally 45 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as possessing anti-inflammatory effects. Finally, 54 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2003–2004, research on the pharmacology of marine natural products which involved investigators from Argentina, Australia, Brazil, Belgium, Canada, China, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Morocco, the Netherlands, New Zealand, Norway, Panama, the Philippines, Portugal, Russia, Slovenia, South Korea, Spain, Thailand, Turkey, United Kingdom, and the United States, contributed numerous chemical leads for the continued global search for novel therapeutic agents with broad spectrum activity. © 2007 Elsevier Inc. All rights reserved. Keywords: Drug-leads; Marine; Metabolites; Natural products; Pharmacology; Review; Toxicology 1. Introduction chemicals whose structures have been established are included in the present review. As in our previous reviews, we have used The purpose of this article is to review the 2003–4primary Schmitz's chemical classification (Schmitz et al., 1993) to assign literature on pharmacological studies with marine natural each marine compound to a major chemical class, namely, products using the same format as in our previous reviews of polyketides, terpenes, nitrogen-containing compounds or poly- the marine pharmacology peer-reviewed literature (Mayer and saccharides. Those publications reporting anthelmintic antibac- Lehmann, 2000), (Mayer and Hamann, 2002, 2004, 2005). terial, anticoagulant, antifungal, antimalarial, antiplatelet, Consistent with our previous reviews, only those articles antiprotozoal, antituberculosis or antiviral properties of 67 marine reporting on the bioactivity or pharmacology of 166 marine chemicals have been tabulated in Table 1 with the corresponding structures shown in Fig. 1. The articles reporting on 45 marine ⁎ Corresponding author. Tel.: +1 630 515 6951; fax: +1 630 971 6414. compounds affecting the cardiovascular, immune and nervous E-mail address: [email protected] (A.M.S. Mayer). systems, as well as those with anti-inflammatory effects are 1532-0456/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.cbpc.2007.01.015 554 A.M.S. Mayer et al. / Comparative Biochemistry and Physiology, Part C 145 (2007) 553–581 Table 1 Marine pharmacology in 2003–4: marine compounds with anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities Drug class Compound/organisma Chemistry Pharmacologic activity MMOAb Countryc References Anthelmintic Thiocyanatins (1–4)/sponge Polyketide d Nematocidal activity to Undetermined AUS (Capon et al., 2004b) Haemonchus contortus Antibacterial Kalihinol Y and X (5,6)/ Diterpene e B. subtilis inhibition Folate biosynthesis PHIL, USA (Bugni et al., 2004) sponge inhibition Antibacterial MC21A (7)/bacterium Bromophenol Methicillin-resistant Permeabilization of JAPN (Isnansetyo et al., 2003) S. aureus inhibition cell membrane comparable to vancomycin Antibacterial Nagelamide A (8)/sponge Alkaloidf M. luteus, B. subtilis and Protein phosphatase AUS, JAPN (Endo et al., 2004) E. coli inhibition 2A inhibition Antibacterial Plicatamide (9)/tunicate Peptidef Methicillin-resistant Bind to plasma USA (Tincu et al., 2003) S. aureus, L. monocytogenes, membrane causing E. coli and P. aeruginosa K+ efflux and inhibition depolarization Antibacterial Manoalide (10)/sponge Sesterterpene e S. aureus inhibition Undetermined JAPN (Namikoshi et al., 2004) Antibacterial Melophlin C (11)/sponge Polyketide d B. subtilis and S. aureus Undetermined CHI, INDO, (Wang et al., 2003a) inhibition GER, NETH Antibacterial Eudistomin X (12)/tunicate Alkaloidf S. aureus, B. subtilis and Undetermined GER (Schupp et al., 2003) E. coli inhibition Antibacterial Dolabellanin B2 (13)/sea hare Peptidef B. subtilis, H. influenza and Undetermined JAPN (Iijima et al., 2003) V. vulnificus inhibition Antibacterial Pseudopterosin X and Y Diterpene e S. aureus, S. pyogenes, and Undetermined CAN, USA (Ata et al., 2004) (14,15)/soft coral E. faecalis inhibition Antibacterial Sinularia lipids (16–18)/ Polyketide d B. subtilis, B. pumilus, Undetermined RUS (Dmitrenok et al., 2003) soft coral E. coli and P. aeruginosa inhibition Antibacterial Rhodomela Bromophenol d S. aureus, S. epidermidis Undetermined CHI (Xu et al., 2003) bromophenol (19)/alga and P. aeruginosa inhibition Antibacterial Cribrostatin 6 (20)/sponge Alkaloidf S. pneumoniae inhibition Undetermined USA (Pettit et al., 2004) Antibacterial Purpuramine L (21)/sponge Bromotyrosine S. aureus, B. subtilis and Undetermined IND (Goud et al., 2003b) alkaloids f C. violaceum inhibition Antibacterial Germacrane (22)/sponge Sesquiterpene e S. aureus and B. subtilis Undetermined THAI (Satitpatipan et al., 2004) inhibition Antibacterial Ptilocaulis Alkaloidf S. aureus inhibition Undetermined USA (Yang et al., 2003c) guanidine (23)/sponge Antibacterial Membranolides C and Diterpene e S. aureus and E. coli Undetermined USA (Ankisetty et al., 2004) D(24,25)/sponge inhibition Antibacterial Arenicins 1 and 2 Peptidef E. coli, L. monocytogenes Undetermined RUS (Ovchinnikova et al., (26,27)/polychaeta and C. albicans inhibition 2004) Antibacterial Perinerin (28)/ Peptidef Gram-negative, Gram- Undetermined CHI (Pan et al., 2004) polychaeta positive and fungal inhibition Antibacterial Hippoglossoides peptide Peptidef P. aeruginosa and S. aureus Undetermined CAN (Patrzykat et al., 2003) (29)/American plaice inhibition Anticoagulant Dysinosin C (30)/sponge Peptidef Factor VIIa and thrombin Two structural AUS (Carroll et al., 2004) inhibition motifs contribute to protease binding Anticoagulant Fucosylated Polysaccharide g Anticoagulant, bleeding Accelerated BRA (Zancan et al., 2004) chondroitin sulfate and antithrombotic effects thrombin inhibition (31)/sea cucumber in vivo Anticoagulant Sulfated galactans Polysaccharide g Antithrombin-mediated Interaction holds BRA (Melo et al., 2004) (32,33)/alga and sea urchin anticoagulant activity antithrombin inactive Antifungal Astroscleridae sterol Sterol sulfated S. cerevisiae inhibition Undetermined USA (Yang et al., 2003b) (34)/sponge Antifungal Dysidea arenaria Terpene e Fluconazole resistance MDR1-type efflux USA (Jacob et al., 2003) sterol (35)/sponge reversal in C. albicans pump inhibition Antifungal Massadine (36)/sponge Alkaloidf Geranylgeranyltransferase I Undetermined JAPN, NETH (Nishimura et al., 2003) inhibition Antifungal Naamine G (37)/sponge Alkaloidf C. herbarum inhibition Undetermined GER, NETH (Hassan et al., 2004) Antifungal Utenospongin B (38)/sponge Diterpene e C. tropicales and Undetermined NETH, MOR, (Rifai et al., 2004) F. oxysporum inhibition PORT Antifungal (2S,3R)-2-aminododecan-3-ol Polyketide d C. albicans inhibition Undetermined BRA, USA (Kossuga et al., 2004) (39)/ascidian Antimalarial Bielschowskysin (40)/coral Diterpene e P. falciparum inhibition Undetermined PAN, USA (Marrero et al., 2004) Antimalarial Briarellins (41–43)/coral Diterpene e P. falciparum inhibition Undetermined PAN, USA (Ospina et al., 2003) A.M.S. Mayer et al. / Comparative Biochemistry and Physiology, Part C 145 (2007) 553–581 555 Table 1 (continued ) Drug class Compound/organisma Chemistry Pharmacologic activity MMOAb Countryc References Antimalarial Cembradiene (44)/sea whip Diterpene e P. falciparum inhibition Undetermined PAN, USA (Wei et al., 2004) Antimalarial Dolastatin 10 (45)/sea hare Peptidef P. falciparum FCH5.C2 Microtubule and USA (Fennell et al., 2003) inhibition mitotic inhibition Antimalarial Manzamine A (46)/sponge Alkaloidf P. falciparum D6 and W2 Undetermined USA (Rao et al., 2003) inhibition Antimalarial Trioxacarcin A and D Glycosided, g P. falciparum strains NF54 Undetermined NETH, GER (Maskey et al., 2004) (48,49)/bacterium