**9. Secondary metabolites derived from Cyanobacteria strains**

Natural bioactive products have been isolated from a varied diversity of strains and verified for numerous biological activities. Among these strains, cyanobacteria strains signify such a source.

Secondary metabolites derived from cyanobacteria strains were identified as a rich source of bioactive compounds [69–71]. Several bioactive compounds isolated from different cyanobacterial strains showed a varied range of chemical structures *Cyanobacteria Natural Products as Sources for Future Directions in* Antibiotic *Drug Discovery DOI: http://dx.doi.org/10.5772/intechopen.106364*

and biological activities comprising new peptides, amides, terpenes, carbohydrates, polyketides, fatty acids, alkaloids, and other organic chemicals [41, 72–74]. These compounds are regarded as good candidates for drug discovery, with functions in the industry [75–77], agriculture [19], and in pharmacy [69, 77, 78].

The cyanobacterial bioactive compounds specify useful pharmaceuticals that are problematic to produce synthetically [79]. The variety of structures found in *Lyngbya majuscula* is just incredible. Compounds isolated from this strain are amino acids, fatty acids, depsipeptides, pyrroles, amides, alkaloids, lactones, lipopeptides, and many others [40, 72, 80, 81]. Totally, cyanobacterial bioactive compounds show an exciting range of biological activities ranging from insecticidal, immunosuppressant, antiviral, anticancer, antimicrobial, and anti-inflammatory to proteinase-inhibiting activities which are outstanding targets of biomedical research (**Table 2**) [ 2, 5–8, 78, 113–118].

### **10. Antiviral activity**

The extension of fatal, virus-related diseases, such as HIV, has resulted in several considerable consequences. Since the only accredited therapy (HAART, highly active antiretroviral therapy) has shown toxic effects, severe induction to viral resistance, and disability to eliminate viral agents, thus the need for new and safe antiviral therapies is an urgent issue [119, 120]. Some potential antiviral compounds are described below:

#### **10.1 Polysaccharides**

Spirulan and Ca-spirulan derived from *Spirulina sp*. are regarded as the most notable antiviral polysaccharide compounds provided their broad-spectrum activity against HIV-1, HIV-2, H, influenza and other enveloped viruses. These compounds disable the reverse transcriptase activity of HIV-1 and prevent the attachment and fusion of virus cells with host cells. Additionally, the fusion between HIV-infected and uninfected CD4+ lymphocytes, which boosts the viral infectivity, is inhibited [29]. Their reduced anticoagulant properties make them more advantageous antiviral agents over other sulfated polysaccharides. Another interesting compound is nostoflan from *Nostoc flagelliforme*, an acidic polysaccharide showing potent virucidal activity against herpes simplex virus-1 [121, 122].

#### **10.2 Carbohydrate-binding proteins**

A couple of carbohydrate-binding proteins have shown promising activity as antiviral agents. Ichthyopeptins A and B, derived from *Microcystis ichthyoblabe*, are potential agents against influenza virus, with an IC50 value of 12.5 mg ml–1 [123]. Cyanovirin-N and scytovirin are also potent virucidal drugs that interfere with several steps of the viral fusion process. Cyanovirin-N, for example, shows both *in vitro* and *in vivo* activity against HIV and other lentiviruses in nanomolar concentrations. These 101 amino acids long, 11 kDa polypeptide derived from *Nostoc ellipsosporum* is being developed as a vaginal gel for preventing sexual transmission of HIV by Cellegy Pharmaceuticals, San Francisco, CA, provided its inhibitory effects upon HIV virus-CD4 cell membrane fusion [124]. Scytovirin, on the other hand, is a 95 amino acid long, 9.7 kDa polypeptide (that includes five intra-chains disulfide bonds) derived


#### *Cyanobacteria – Recent Advances and New Perspectives*


*Cyanobacteria Natural Products as Sources for Future Directions in* Antibiotic *Drug Discovery DOI: http://dx.doi.org/10.5772/intechopen.106364*


**Table 2.** *Bioactive compounds from cyanobacteria.* *Cyanobacteria Natural Products as Sources for Future Directions in* Antibiotic *Drug Discovery DOI: http://dx.doi.org/10.5772/intechopen.106364*

from aqueous extracts of *Scytonema varium*, that is able to attach to the glycoprotein envelope of HIV (gp120, gp160, and gp41), thus making the virus inactive even in low nanomolar concentrations [125].

#### **10.3 Sulfoglycolipids**

Natural cyanobacterial sulfoglycolipids show confirmed HIV-reverse transcriptase and DNA polymerase inhibitory effects [29].

### **11. Antibacterial activity**

If bacterial resistance strengthens, the treatment may become impossible for some diseases. Nosocomial infections such as those caused by the methicillin-resistant *Staphylococcus aureus* or the vancomycin-resistant enterococci, caused by multidrug-resistant bacteria, create therapeutic problems of worldwide concern [126], hence the urgency of developing new antibiotics. Accordingly, new attempts to find antibacterial activity via screening of cyanobacterial extracts have started [127], although very few cyanobacteria-related antibacterial compounds have been detected to date. Noscomin57, from *Nostoc commune* [128], shows antibacterial activity against *Bacillus cereus, Staphylococcus Epidermidis,* and *Escherichia coli*. Antibacterial activity of Anabaena extracts against vancomycin-resistant S. aureus with a MIC of 32–64 mg ml-1 has been reported by [129].

### **12. Antiprotozoal activity**

The estimations of the World Health Organization indicate that >109 people over the world suffer from tropical diseases caused by *Schistosoma, Trypanosoma*, *Leishmania, Plasmodium,* and others [130]. The unsuccessful treatment of such diseases (especially malaria) is related to the growing resistance shown by these protozoa and the slow pace of drug discovery [131, 132]. In a recent project operated by the Panamanian International Co-operative Biodiversity Group, five classes of antiprotozoal compounds were isolated from cyanobacteria*. Nostocarboline*, an alkaloid protease inhibitor isolated from *Nostoc sp.* 78-12 A, displayed activity against *T. cruzi, Leishmania donovani, Trypanosoma brucei,* and *Plasmodium falciparum* [133]*.* Moreover, aerucyclamide C68 isolated from *Microcystis aeruginosa PCC 7806* has been also detected to be active against *T. brucei.*

### **13. Protease inhibition activity**

More than 120 cyanobacterial alkaloids with various biological activities (including protease inhibition) were introduced between 2001 and 2006. Some of these compounds, such as microginins (used for the treatment of high blood pressure), aeruginosins, and cyanopeptolins (a serine inhibitor used for asthma and viral infections) are described by Jaspars and Lawton [29]. Kempopeptins are other groups of protease inhibitory products, for example, kempopeptin B (with activity against trypsin, with an IC50 of 8.4 mM), kempopeptin A (a cyclodepsipeptide derived from marine *Lyngbya* with activity against elastase), and chymotrypsin with an IC50 of 0.32 mM and 2.6 mM, respectively [46].
