A Review on bioactive Secondary Metabolites Reported from Actinomycetes Isolated from Marine soil Samples of Indian Peninsula

 

Lokesh Ravi, Krishnan Kannabiran*

Department of Biomedical Sciences, School of Biosciences and Technology, VIT University, Tamil Nadu, INDIA

*Corresponding Author E-mail: kkb@vit.ac.in

 

ABSTRACT:

The aim of this review is to give an update on actinobacteria derived bioactive secondary metabolites reported from Indian Peninsula. Several research groups in India are working on actinomycetes diversityand focusing more on antimicrobial, antiparasitic, anticancer activity and enzymes produced by these species. Several reports are available on multiple biological activitiesof culture filtrate/ crude extracts obtained from actinomycetes isolates. Bioactivity guided extraction, purification andcompound identification has yielded several novel compounds. Scalable production of bioactive compounds from potential actinomycetes is under different phases of clinical trials for drug development as antibiotics worldwide.  Currently actinomycetes research is more intense and more predominant not only in India but throughout the world due to its well-known ability to produce novel antibiotics and new chemical entities. The demand for new antibiotics from marine actinomycetes to overcome microbial drug resistance and to develop a new anticancer drug leads is ever persistent. Several novel antibiotics and anticancer metabolites are already been reported from actinomycetes in the recent past. In this review the bioactive compounds reported from marine actinomycetes species isolated from samples collected at various locations of IndianPeninsula has been reviewed.. The focus of the present review is to summarize the antimicrobial (antibacterial-ESBL, MRSA, VRE, antidermatophytic and anticandidal) and anticancer secondary metabolites reported from actinomycetes.

 

KEYWORDS: Actinomycetes, Secondary metabolites, Antimicrobial, Antiparasitic, Anticancer.

 

 


INTRODUCTION:

Actinomycetes are considered as natures treasure chest for numerous novel secondary metabolites and new chemical entities. With an ever increasing health issues throughout the world, the demand for control through treatment and cure for such issues increases faster than ever. As researchers ran out of options for cure/control of diseases using the existing drugs, due to toxicity, side effects, effect on long-term use, etc., most of them are now exploring the natural sources for effective and safer bioactive molecules1. Phytochemicals and microbial secondary metabolites are the natural source and they have proven to have many advantages over the chemically synthesized compounds.

 

While looking into the natural source for bioactive molecules, medicinal plants are already been explored to a large extent. As, phytochemicals were extensively studied in the last few decades worldwide, researchers are now started exploring more on marine actinomycetes. Actinomycetes have already provided several secondary metabolites of commercial and therapeutic values2. The actinomycetes diversity and their secondary metabolites need to be explored further from the unexploited marine sources of India3.

 

Actinomycetes are soil microbes, which play a significant role in the food web as the decomposers and recycler of nutrients. The “Earthy Smell” obtained during rainy season, is due to the volatile compound “geosmin” produced by these actinomycetes in the soil4. Actinomycetes are well known for its ability to produce antibiotics, especially the genus Streptomyces which produced more than 70% antibiotics available in the market5.  Several secondary metabolites obtained from actinomycetes exhibited strong bioactivity. These actinomycetes habitats in all types of soils like, agricultural, rhizosphere, barren-lands, marine, mangroves, volcano, ice point, mountains, forests, etc,6. Studies on actinomycetes have accelerated greatly in the last decade and actinomycetes research has taken the stage in many parts of India. Number of publications in actinomycetes research in India has increased considerably during 2011-2015, while comparing to 2001-20107. In this review, the summary of major biological studies carried out with the bioactive secondary metabolites extracted from actinomycetes in the last two decades in India was discussed. The number of sampling sites for actinomycetes isolation is plotted in Google-maps. As it is evident from Figure1, majority of the sampling sites are in the southern part of the country.    Isolation of actinomycetes from marine habitats has improved in the recent years, due to the novelty of the various secondary metabolites and enzymes produced by them. A review published in the year 2007 states that, 8 genera and 41 species of marine actinobacteria has been reported from the Indian peninsula8. India being a tropical country with rich source of unexplored ecosystems and not been completely explored for novel actinomycetes and their secondary metabolites. Although the natural resources are balanced throughout the country, the southern part of the country has the advantage of both fertile and marine ecosystems, which could be a reason for more research on actinomycetes in the southern part of the country. This could be due to the obvious fact that Bay of Bengal and Arabian Sea are bordering the southern part of the country and southern states are quite rich in forest, mountain and fertile lands. Few reports are also available on actinomycetes isolated from Andaman and Nicobar Islands and its bioactivity. Even though many reports are available on marine actinomycetes derived bioactive compounds in India, in this review the bioactive compounds isolated and identified from marine actinomycetes species isolated from Indian Peninsula.

 

Antibacterial secondary metabolites from actinomycetes:

Actinomycetes (Phylum: Actinobacteria) are well-known for their ability to produce a several natural products with high structural complexity and with diverse biological activities9. Actinomycetes isolated from Indian peninsula are widely studied for antibacterial activity due to the ease of doing in vitro study and low cost of consumables required for antibacterial analysis. Not many reports are available on antibacterial activity of extracted and identified secondary metabolites from actinomycetes. Many researchers arenow focusing their studies on identifying antibacterial secondary metabolites from actinomycetes. Bacterial drug resistance is the major problem for the control and management of bacterial diseases; currently it poses a big challenge for the treatment of urinary react infections (UTI). Resistance to existing drugs are constantly being reported from all parts of the world and it creates a huge demand for identification of new drug molecules that targets these resistant pathogens. Actinomycetes have proven its ability to produce novel secondary metabolites that has strong antibacterial activity against these drug-resistant pathogens10.

 

Antibacterial compounds extracted from marine actinomycetes are given in Table1. Anti-MRSA anti VRE compound 2, 4-dichloro-5-sulfamoylbenzoic acid (DSBA) was extracted from Streptomyces sp. VITBRK3. It showed significant anti-MRSA (MIC 0.5 μg/ml) and anti-VRE (160 μg/ml) activity11.Bhave et al. (2015)10 has identified Mithramycin active against drug resistant pathogens such as methicillin sensitive Staphylococcus aureus (MSSA), methicillin resistant Staphylococcus aureus (MRSA), vancomycin sensitive Enterococci (VSE) and vancomycin resistant Enterococci (VRE) pathogensproduced by Streptomyces sp. PM1129877 isolated from Playa region of Rajasthan, India. Abirami et al. (2015)12 has reported the extraction of antibacterial secondary metabolite coumarin-6-ol, 3,4-dihydro-4,4,5,7-tetramethyl (CDTM) isolated from Streptomyces sp. VITAK1 from marine soil samples of Andaman and Nicobar Islands. The lead compound demonstrated a significant antibacterial activity with an IC50 value of 2.5-40µg/ml against the studied bacterial. Janardhan et al.(2014)13 has reportedthe extraction of antibacterial secondary metabolite, (Z)-1-((1-hydroxypenta-2,4-dien-1-yl)oxy) antracene-9,10-dione from Nocardiopsis albafrom mangrove soils of Nellur, Andhra Pradesh, India. Subhashini and Kannabiran(2014)14have reported the extraction of anti-ESBL compound 1, 2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester (DMEHE) from Streptomyces sp. VITSJK8. DMEHE showed high antagonistic activity against Klebsiella pneumoniae (VITEB8) with the MIC value of 0.125 μg mL-1, Klebsiella pneumonia (VITEB6) with the MIC value of 0.25μg mL-1 and againstKlebsiella pneumonia (VITEB1)with the MIC value of 2.0μg mL-1.Shetty et al. (2014)15 has reported the antibacterial antibiotic, actinomycin D produced by Streptomyces parvulus. Actinomycin D exhibited activity against both Gram positive and Gram negative bacteria and it also inhibited streptomycin resistant bacteria Bacillus cereus and Pseudomonas putida.Nandhini and Selvam (2013)16 has reported two antibacterial secondary metabolites, i) 3-ethyl,3-methyl heptanes and ii) Diisodecyl ether, produced by Streptomyces coelicolor strain SU6, a marine actinomycetes isolate. Holkar et al. (2013)17 has reported three rhodomycin analogues, i.e; i) Rhodomycin B, ii) α2-Rhodomycin II and iii) Obelmycin, produced by Streptomyces purpurascens. Rhodomycin B demonstrated promising antibacterial activity with an MIC value of 2µg/ml against Bacillus subtilis.

 

Kadiri et al.(2013)18 has identified a novel aporphine alkaloid SSV, produced by Streptomycessp. KS1908.  The secondary metabolite was identified based on bioactivity guided purification, against 11 bacterial and dermatophytic human pathogens. Singh et al, 2012 has analysed the interactions of secondary metabolite, 2-methylheptyl isonicotinate produced by Streptomyces sp. 201 with dihydrodipicolinate enzyme in Mycobacterium tuberculosis, using molecular docking studies.Saurav and Kannabiran (2012)19 has identified 5-(2,4-dimethylbenzyl) pyrrolidin-2-one, a secondary metabolite produced by Streptomycessp. VITSVK5. It showed MIC value of 187µg/ml against Escherichia coli.Franco et al. (1991)20 has reported a bioactivity secondary metabolite, alisamycin produced by Streptomyces actuosus. The compound displayed strong activity against E.coli, S.aureus, and S.faecalis, with a lowest MIC value of 3.2µg/ml against S.aureus Franco et al. (1991)20. He has reported another antibiotic, butalactin produced by Streptomyces corchorusii. This antibiotic demonstrated strong activity against S.aureus, S.epidermis, S.faecalis E.coliand S.haemolyticus, with highest activity against S.faecalis.Franco et al (1987)21reported their first antibiotic swalpamycin, produced by Streptomyces anandii. It was studied against various bacterial pathogens S.aureus, S.faecalis, B.subtilis, P.vulgaris, P.aeruginosa, with highest activity against B.subtilis and M.luteus.


 

Table.1: Antibacterial compounds reported from actinomycetes isolated from Indian        Peninsula

Molecule

Organism

Activity

References

2, 4-dichloro-5-sulfamoylbenzoic acid

Streptomyces sp. VITBRK3

Anti-MRSA and anti-VRE

11

Mithramycin

Streptomyces sp. PM1129877

Anti- MRSA and anti-VRE

10

 [Coumarin-6ol,3,4-Dihydro-4,4,5,7-TetraMethyl]

Streptomyces sp. VITAK1

Antibacterial

12

Z-1-((1-hydroxypenta -2,4-dien-oxy)anthracene-9,10-dione

Nocardiopsis alba

Antibacterial

13

1, 2-Benzenedicarboxylic Acid, Mono(2-Ethylhexyl) Ester

Streptomyces sp strain VITSJK8

Antibacterial – ESBL pathogens

14

Actinomycin D

Streptomyces parvulus

Antibacterial

15

3-ethyl,3-methyl heptanes,

Diisodecyl ether

Streptomyces coelicolorstrain SU6

Antibacterial

16

Rhodomycin B, α2-Rhodomycin II, and Obelmycin

Streptomyces purpurascens

Antibacterial

17

Aporphine alkaloid SSV

Streptomyces

sp. KS1908

Antibacterial

18

2-methylheptylisonicotinate

Streptomyces sp. 201

Antituberculosis

25

5-(2,4-dimethylbenzyl) pyrrolidin-2-one

Streptomyces VITSVK5 spp.

Antibacterial

32

Alisamycin

Streptomyces actuosus

Antibacterial

20

Butalactin

Streptomyces corchorusii

Antibacterial

20

Swalpamycin

Streptomyces anandii

Antibacterial

21

 


Quorum sensing inhibitor and quorum quenching compounds from actinomycetes:

The growing emergence of antibiotic-resistant pathogens is a concern to human health care and warrants the urgent need for the development of alternative therapeutic strategies. Quorum sensing is a cell to cell communication system prevailed by the microorganisms for its survival. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, it is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division.There are three types of quorum sensing system in bacteria such as N-acyl homoserine lactones (AHL) (AI-1), Oligopeptide and universal Autoinducer (AI-2). A large number of gram-negative quorum-sensing systems studied so far utilize aAHLs signal molecules. The gram positive organism uses LuxI/LuxR signaling molecules. Microbial quorum sensing leads to the formation of biofilm. These biofilms are the first step for the virulence of pathogen and also responsible for imparting resistance.Inactivation of quorum sensing system is generally known as quorum quenching (QQ). Many natural quorum quenching (QQ) agents have been identified which include QQ inhibitors and QQ enzymes. QS inhibitor compounds inactivate QS by different quorum quenching (QQ) mechanisms including enzymatic inactivation of the signal molecule, inhibition of signal biosynthesis, and inhibition of signal detection. More than 30 species of marine QQ bacteria have been identified so far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy. Actinomycetes are a remarkable type of bacteria found in a wide range of aquatic and terrestrial environments and, highly attractive as cell factories or bioreactors for production of QQ compounds or Quorum sensing inhibitors (QSI).

In India reports on application of actinomycetes or its secondary metabolites as QSI or QQ compound against drug resistant bacterial pathogens was limited. The yellow pigment produced by actinomycetes strain C5-5Y was reported to possess QQ activity against two clinical pathogens tested22.  It was reported that sponge-associated actinomycetes belonging to genus Streptomyces NIO 10068, NIO 10058 and NIO 10090 exhibited very good anti-QS activity. Cinnamic acid and linear dipeptides proline–glycine and N-amido-a-proline were extracted from NIO 10090.  These secondary metabolites exhibited a significant effect on virulence factors in P. aeruginosa (ATCC 27853) by down regulating QS-mediated virulence factors like swarming, biofilm formation, pyocyanin, rhamnolipid and LasA production23. QQ ability in many actinobacteria has a great potential in controlling the spread of plant and animal pathogens24. QS is known to play a major role in the regulation of secondary metabolite production, especially, antibiotics, and morphogenesis in the phylum Actinobacteria. The g-butyrolactone system, methylenomycin furans, AI-2 and other putative AHL-like signalling (QS) molecules have also been reported in Actinobacteria. GBL-based quorum sensing has also been attributed in the Streptomyces genus24. Compounds derived from actinomycetes capable of inhibiting bacterial biofilm formation are given in Table 2.

 

Recently, it was reported that the development of novel Swarna (gold)-based herbo-metallic colloidal nano-formulation for attenuating QS signalling in Streptococcus mutans. Development of new tools 'QS nano-inhibitors’’ to minimize the resistance in treating infectious diseases has also been reported25. Use of biogenic nano-factories to generate novel antivirulence agents that target the communication networks of QS pathogenic bacteria are in progress25.

 


 

Table 2: Antibiofilm compounds reported from actinomycetes isolates from Indian Peninsula

Molecule

Organism

Activity

References

Yellow pigment

Actionmycetes C5-5Y

Quorum quenching

Soundari et al 2012

Cinnamic acid

Streptomyces NIO-10090

Anti-quorum sensing

Naik et al 2012

G-butyrolactone

Actinobacteria

GBL quorum sensing

Polkade et al 2016

Pigment

Streptomyces sp. D25

Antibiofilm activity

Radhakrishnan et al 2016

Swarna (gold)-based herbo-metallic colloidal nano-formulation

Actinobacteria

QS nano-inhibitors

Singh et al 2016

 


Antifungal compoundsfrom actinomycetes:

Antifungal compounds extracted from marine actinomycetes are given in Table 3.Treating fungal infections are very difficult because, fungi are eukaryotic and they are similar to that of humansin several cellular mechanisms and thus making it quite challenging to find out specific drug molecules that selectively targets fungi. Actinomycetes serve as a vital source for antifungal secondary metabolites. Many reports are available on antifungal activity of cell free supernatant and crude solvent extracts from actinomycetes against fungal pathogens,but studies with purified and identified compounds are still scanty. Hence, it is more appropriate to list out theantifungal compounds reported from actinomycetes isolated from Indian Peninsula. Dermatophytic fungal infections are increasing constantly worldwide26;many researchers are currently looking for antidermatophytic compounds from actinomycetes.

 

Ambavane et al. (2014)27 has identified the antifungal compound caerulomycin A from Actinoalloteichus sp. isolated from marine invertebrate from Anjuna Beach, Goa, India. It demonstrated a very low MIC value of 0.39µg/ml to 1.56µg/ml against human pathogenic fungi. Sanjenbam et al. (2014)28has identified an anticandidal secondary metabolite pyrrolo[1,2-a] pyrazine-1,4-dione,hexahydro-3-(phenylmethyl) from Streptomyces sp. VITPK9. The active compound demonstrated significant MIC value of 0.78 to 2.0µg/ml against pathogenic Candida species.Kadiri et al. (2013)18 reported a novel antibiotic compound Aporphine Alkaloid SSV, produced by Streptomyces sp. KS1908.  The compound demonstrated good antifungal activity, against A.niger, A.awamori, C.alibcans and T. rubru.Saurav and Kannabiran (2012a)19 has identified an antifungal secondary metabolite 5-(2,4-dimethylbenzyl) pyrrolidin-2-one (DMBPO) from marine Streptomyces sp. VITSVK5 active against drug resistant Aspergillus clinical isolates.Deepika et al. (2012)29 has reported the isolation of (2S,5R,6R)- 2-hydroxy- 3,5,6- trimethyloctan-4-one (HTMO) from Streptomyces spp. VITDDK3. HTMO showed the MICvalue of 300µg/ml and 240µg/ml against Trichophyton rubrum and Microsporum gypseum respectively. The MIC value for Gram negative bacteria was 200-320 µg/ml and Bacillus cereus was 370µg/ml. Similarly the MIC value for Aspergillus fumigatus was 225 µg/ml and Aspergillus flavus was 340 µg/ml. Thenmozhi and Kannabiran (2012)30has reported the antifungal activity of four compounds, cyclopentanepropanoic acid, 3,5-bis(acetyloxy)-2-[3-(methoxyimino) octyl], methyl ester (1); 5-azidomethyl-3-(2-ethoxycarbonyl-ethyl)-4-ethoxycarbonylmethyl-1H-pyrrole-2-carboxylic acid, ethyl ester (2); and akuammilan-16-carboxylic acid,17-(acetyloxy)-10-methoxy, methyl ester (16R)(3);from Streptomyces sp. VITSTK7 and demonstrated a significant MIC value of 0.25mg/ml against Aspergillus fumigatus.Dhanasekaran et al.(2008)31has reported the isolation of novel antifungal compound 4-phenyl-1-napthyl phenyl acetamide, from Streptomyces sp. DPTB16. Franco et al. (1991)20has reported an antibiotic secondary


 

Table3: List of antifungal compounds reported from actinomycetes isolated from Indian Peninsula

Molecule

Organism

Activity

References

Caerulomycin A

Actinoalloteichus species

Antifungal

27

Pyrrolo[1,2-a]Pyrazine-1,4-dione,hexahydro-3-(phenylmethyl)

Streptomyces sp. VITPK9

Anticandidal

28

Aporphine alkaloid SSV

Streptomyces

sp. KS1908

Antifungal, Anticandidal and Antidermatophyte

18

5-(2,4-dimethylbenzyl)pyrrolidin-2-one

Streptomyces VITSVK5 spp.

Antifungal and antiparasitic

6

2S,5R,6R)- 2-hydroxy- 3,5,6- trimethyloctan-4-one (HTMO)

Streptomyces spp. VITDDK3

Antifungal, antidermatophytic and antiparasitic

29

Cyclopentanepropanoic acid, 3,5-bis(acetyloxy)-2-[3-(methoxyimino) octyl], methyl ester

5-azidomethyl-3-(2-ethoxycarbonyl-ethyl)-4-ethoxycarbonylmethyl-1H-pyrrole-2-carboxylic acid, ethyl ester

Akuammilan-16-carboxylic acid,17-(acetyloxy)-10-methoxy, methyl ester (16R)

Streptomyces sp. VITSTK7

Antifungal and antiparasitic

30

4-phenyl-1-napthyl phenyl acetamide

Streptomyces sp. DPTB16

Antifungal

31

Alisamycin

Streptomyces actuosus

Anticandidal

20

Swalpamycin

Streptomyces anandii

Antifungal

21

 


metabolite, alisamycin, produced by Streptomyces actuosus. It demonstrated a goodantifungal activity against C.albicans, with low MIC value of 50µg/ml. Franco et al. (1987)21 has reported another antibiotic secondary metabolite, swalpamycin, produced by Streptomyces anandii and this compound also demonstrated a good antifungal activity against, A.niger and C.albicans.

 

Antiparasitic compounds from actinomycetes:

Antiparasitic compound HTMO extracted from marine Streptomyces spp. VITDDK3 showed 100% mortality against the A. subpictus larvae at 200 ppm concentration with the LC50 value of 69.65 mg/L; whereas mortality was observed at 250 ppm concentration against Culex quinquefasciatus, Rhipicephalus microplus and adult Pediculus humanus capitis with the LC50 and r2 values against the larvae of R. microplus (94.49 ppm; 0.982); A. subpictus (69.65 ppm; 0.906), and against C. quinquefasciatus (82.82ppm; 0.957), respectively29. DMPBO extracted from Streptomyces sp. VITSVK5 showed the larval mortality with the LC50 and r2 values against the larvae of R. microplus (84.31 ppm; 0.889); A. stephensi (88.97 ppm; 0.817), and C. tritaeniorhynchus (74.95ppm; 0.781), respectively32. Three compounds extracted from Streptomyces sp. VITSTK7, cyclopentanepropanoic acid, 3,5-bis(acetyloxy)-2-[3-(methoxyimino) octyl], methyl ester (1); 5-azidomethyl-3-(2-ethoxycarbonyl-ethyl)-4-ethoxycarbonylmethyl-1H-pyrrole-2-carboxylic acid, ethyl ester (2); and akuammilan-16-carboxylic acid,17-(acetyloxy)-10-methoxy, methyl ester (16R)(3); showed antiparasitic activity synergistically33.

 

Anticancer compounds from actinomycetes:

Suthindhiran and Kannabiran (2013)34 has reported a cytotoxic secondary metabolite, furan 2-ylacetate (F2A), produced by marine Streptomyces sp. VITSDK1.  F2A has demonstrated cytotoxic activity against various cancer cells, with an average IC50 value of 15µg/ml. F2A mediated apoptosison HeLa cell line was reported through MTT analysis. List of anticancer compounds reported from actinomycetes isolated from marine soil samples collected from Indian Peninsula Holkar et al.(2013)17 has reported a cytotoxic secondary metabolite rhodomycin B, produced by Streptomyces purpurascens. It demonstrated anticancer activity against HeLa cell line, with an IC50 value of 8.8µg/ml. Kadiri et al. (2013)18 has reported thenovel secondary metabolite aprophine alkaloid SSV, produced by Streptomycessp. KS190. This compound demonstrated strong anticancer activity against Hep2, HeLa, HL-60 and MCF7 cell lines. It showed the IC50 value was 1.1µg/ml against Hep2 cell line.Saurav and Kannabiran (2012b) 35has reported the cytotoxic activity of DMPO, produced by Streptomyces VITSVK5 spp. DMPO demonstrated cytotoxic activity on HEP2 cell line with IC50 of 2.8µg/ml andIC50 of 8.3µg/mlagainst HepG2 cell line. Gorajana et al. (2005)36has reported 1-Hydroxy-1-norresistomycin, produced by Streptomyces chibaensis AUBN1/7, that demonstrated strong activity against HMO2 and Hep2 cell lines. Franco et al. (1991)20 has reported an antibiotic antitumor compound alisamycin produced by Streptomyces actuosus. It showed weak antitumor activity against cancer cells. Isolation of novel compound N-(4-aminocyclooctyl)-3, 5-dinitrobenzamide from the Mangrove-associated actinomycete Pseudonocardiaendophytica VUK-10 active against cancer cell lines MDA-MB-231, OAW-42, HeLa, and MCF-7 reveal that HELA cells are most susceptible (IC50-10 nM37.


Table 4. Anticancer compounds reported from actinomcetes

Molecule

Organism

Activity

References

Furan 2-ylacetate

Streptomyces sp. VITSDK1

Cytotixicity – HeLa cell lines

34

Rhodomycin B

 

Streptomyces purpurascens

Cytotoxicity – HeLa cell lines

17

Aporphine alkaloid SSV

Streptomyces

sp. KS1908

Cytotoxicity – Hep2, HeLa, HL-60 and MCF7

18

5-(2,4-dimethylbenzyl)pyrrolidin-2-one

Streptomyces VITSVK5 spp.

Cytotoxicity – HEP2 and HEPG2

35

1-Hydroxy-1-norresistomycin

StreptomyceschibaensisAUBN1/7

Cytotoxicity – HePG2 and HMO2

36

Alisamycin

Streptomyces actuosus

Antitumor

20

N-(4-aminocyclooctyl)-3, 5-dinitrobenzamide

Pseudonocardiaendophytica VUK-10

Antitumor

37

 


CONCLUSION:

This review provides the recent research updates on actinomycetes derived compounds in India.Southern part of India has the advantage both fertile and marine ecosystems, thus contributing more towards actinomycetes research. Although many publications have been made in the last five years, most of these reports are pertaining to bioactivity of culture filtrates and different solvent extracts prepared from actinomycetes, as they fail to identify the active secondary metabolites responsible for bioactivity. Hence marine actinomycetes research in India has to be reoriented towards isolation of potential/novel species from unexplored area and extraction and identification bioactive compoundsand new chemical entities. Already reported bioactive compounds can be developed as therapeutic molecules by doing enough clinical trials to develop as a drug.

 

ACKNOWLEDGEMENT:

The authors would like to thank the management of VIT University for encouraging us to write this review.

 

CONFLICT OF INTEREST:

Authors declared no conflict of interest.

 

REFERENCES:

1.        Sharma SB, Gupta R. Drug development from natural resource: a systemic approach. Mini-Reviews in Medicinal Chemistry. 2015; 15(1): 52-57.

2.        Zhu H, Sandiford SK, van Wezel GP. Triggers and cues that activate antibiotic production by actinomycetes. Journal of Industrial Microbiology and Biotechnology. 2014; 41 (2): 371-386.

3.        Baskar V, Subha K, Paneerselvam A. Diversity of actinomycetes- a review. International Journal of Scentific Research and Development. 2015;3(4): 1162-1165.

4.        GerberNN, Lechevalier HA. Geosmin, an earthy-smelling substance isolated from actinomycetes. Applied Microbiology. 1965;13(6); 935–938.

5.        Procopio RE de L, Silva IR da, Martins MK, Azevedo JL de Araujo JM de. Antibiotics produced by Streptomyces. The Brazilian Journal of Infectious Diseases.2012;16(5): 466–471.

6.        Kumar R, Biswas K, Solanki V, Kumar P, Tarafdar A. Actinomycetes: potential bioresource for human welfare: a review. Research Journal of Chemical and Environmental Sciences.2014; 2(3):5-16.

7.        Velho-pereira S, Kamat NM. Actinobacteriological research in India. Indian Journal ofExperimental Biology.2013:51: 573–596.

8.        Maloy KS, Sahu K, KannanTL. Research on marine actinobacteria in India. Indian Journal of Microbiology.2007; 47: 186–196.

9.        Abdelmohsen UR, Grkovic T, Balasubramanian S, Kamel MS, Quinn RJ,  Hentschel U. Elicitation of secondary metabolism in actinomycetes. Biotechnology Advances.2015;33(6): 798–811.

10.     Bhave SV, Sawant AV, ShanbhagP, Parab RR, Ranadive PV, MishraPD, Mahajan GB.  Fermentation , isolation of mithramycin from Streptomyces of Playa Region and its novel anti- MRSA and anti-VRE activity. SOJ Microbiolog and Infectious Diseases, 2015;3(2): 1–8.

11.     Rajan BM, Kannabiran K. Antibiotic potency of 2,4-dichloro-5-sulfamoyl benzoic acid extracted from marine bacterium streptomyces sp. VITBRK3 against methicilin resistant Staphylococcus aureus.Der Pharmacia Lettre.2015;7(6):244-252

12.     Abirami M, Gopal JV,  Kannabiran K. Extraction and identification of antibacterial compound from marine Streptomyces sp . VITAK1 isolated from the coast of Andaman and Nicobar Islands, India . Applied Biochemistry and Microbiology.2015;51(4): 406–410.

13.     Janardhan A, Kumar AP, Viswanath B, Saigopal DVR,  Narasimha G. Production of bioactive compunds by actinomycetes and their antioxidant properties. Biotechnology Research International, 2014; 217030.

14.     Subashini E, Kannabiran K. Isolation and identification of anti-ESBL ( extended spectrum β -lactamase ) compound from marine Streptomyces sp . VITSJK8.         Journal of Advanced Scientific Research.2014;5(3): 13–18.

15.     Shetty, P. R., Buddana, S. K., Tatipamula, V. B., Naga, Y. V. V., and Ahmad, J. (2014). Production of polypeptide antibiotic from Streptomyces parvulus and its antibacterial activity. Brazilian Journal of Microbiology, 45(1), 303–312.

16.     Nandhini S, Selvam M. Bioactive compounds produced by Streptomyces strain. International Journal of Pharmacy and Pharmaceutical Sciences.2013;5: 13–15.

17.     Holkar S, Begde D, Nashikkar N, Kadam T, Upadhyay A. Rhodomycin analogues from Streptomyces purpurascens: isolation, characterization and biological activities. SpringerPlus. 2013;2(1); 93.

18.     Kadiri S, Yarla NS, Vidavalur S. Isolation and identification of anovel aporphine alkaloid SSV, an antitumor antibiotic from fermented broth of marine associated Streptomyces sp. KS1908. Journal of Marine Science Research and Development. 2013;3(4): 1000137.

19.     Saurav K, Kannabiran K. Cytotoxicity and antioxidant activity from marine Streptomyces VITSVK5 spp . Saudi Journal of Biological Sciences.2012a;19: 81–86.

20.     Franco CMM, Maurya R, Vijayakumar EK, Chatterjee S, Blumbach J, Ganguli BN.  Alisamycin, a new antibiotic of the manumycin group I. Taxonomy, production, isolation and biological activity.The Journal of Antibiotics.1991;44(12): 1289–1293.

21.     Franco CMM, GandhiJN, Chatterjee S, GanguliBN. Taxonomyof the producing strain collected near Pune , Maharashtra State , India . The strain has been deposited at the Deutsches Sammlungvon Mikroorganismen, Gottingen. The Journal of Antibiotics. 1987;XL(10): 1361–1367.

22.     Soundari APG, C. Nagarajan, V. Manon Mani, V. Brindha Priyadarisini. Quorum quenching activity of pigments produced by actinomycetes. International Journal of Science and Research, 2014; 3: 2252-2257.

23.     Naik DN, Wahidullah S, Meena RM. Attenuation of Pseudomonas aeruginosa virulence by            marine invertebrate–der ived Strept omyces sp. Letters in Applied Microbiology. 2012; 56: 197-207.

24.     Polkade AV, Mantri SS, Patwekar UJ, Jangid K. Quorum sensing: An under-explored phenomenon in the phylum Actinobacteria. Frontiers in Microbiology, 2016;7: Article 131.

25.     Singh BN, Prateeksha, Upreti DK, Singh BR, Defoirdt T,  Gupta VK, De Souza AO, Singh HB, Barreira JCM, Ferreira ICFR and  Vahabi,K. Bactericidal, quorum quenching and anti-biofilm nanofactories: a new niche for nanotechnologists. Critical Reviews in Biotechnology, 2016; DOI:10.1080/07388551.2016.1199010.

26.     Ilikit M, Durdu M. Tinea pedis, the etiology and global epidemiology of a commom fungal infection. Critical Reviews in Microbiology. 2015;41(3): 374-388.

27.     Ambavane V, Tokdar P, Parab R, Mahajan G, Mishra PD, Ranadive P. Caerulomycin A — An antifungal compound isolated from marine actinomycetes. Advances in Microbiology, 2014;4: 567–578.

28.     Sanjenbam P, Gopal JV, Kannabiran K. Isolation and identification of anticandidal compound from Streptomyces sp . VITPK9 1.Applied Biochemistry and Microbiology,2014: 50(5): 492–499.

29.     Deepika T, Kannabiran K, Khanna V, Rajakumar G, Jayaseelan C, Santhoshkumar T, Rahuman A. Isolation and characterisation of acaricidal and larvicidal novel compound (2S, 5R, 6R)-2-hydroxy-3,5,6-trimethyloctan-4-one from Streptomyces sp. against blood sucking parasites. Parasiology Research. 2012;111(2): 1151–1163.

30.     Themmozhi M, Krishnan K. Antimicrobial and antioxidant properties of marine actinomycetes Streptomyces sp. VITSTK7. Oxidants and Antioxidants in Medical Science2012: 1(1): 51–57.

31.     Dhanasekran D, Thajuddin N, Pannerselvam A. An antifungal compound: 4-phenyl-1-napthyl-phenyl acetamide from Streptomyces sp.  DPTB16.Facta Universitatis, Series: Medicine and Biology, 2008; 15 (1); 7–12.

32.     Saurav K, Rajakumar G, Kannabiran K, Rahuman A, Velayutham K, Elango G,Zahir A.  Larvicidal activity of isolated compound 5-(2,4-dimethylbenzyl) pyrrolidin-2-one from marine Streptomyces VITSVK5 sp. against Rhipicephalus (Boophilus) microplus, Anopheles stephensi, and culex tritaeniorhynchus. Parasitology Research.2013;112(1): 215–26.

33.     Saurav K,  Kannabiran, K.. In vitro activity of 5- ( 2 , 4-dimethylbenzyl ) pyrrolidin-2-one extracted from marine Streptomyces VITSVK5 spp . against fungal and bacterial human pathogens. Revista Iberoamericana de Micologia. 2012b;29(1): 29–33.

34.     Thenmozhi M, Gopal J, Kannabiran K, Rajakumar G, Velayutham K, Rahuman A. Eco-friendly approach using marine actinobacteria and its compounds to control ticks and mosquitoes. Parasitology Research.2013:112(2): 79–729.

35.     Suthindhiran K, Kannabiran K. Probin the mechanism of cytotoxic furan 2-YL acetate using in vitro and in Silico analysis-pharmacological study. Journal of Pharmacology and Toxicology.2013;8(1): 1–18.

36.     Gorajana A, Kurada BV, Peela S, Jangam P, Vinjamuri S, Poluri E,  Zeeck A. 1-Hydroxy-1-norresistomycin, a new cytotoxic compound from a marine actinomycete, Streptomyces chibaensis AUBN1/7. Journal of Antibiotics. 2005;58(8); 526–529.

37.     Mangamuri UK, Vijayalakshmi M, Poda S, Manavathi B, Chitturi B,Yenamandra V. Isolation and biological evaluation of N-(4-aminocyclooctyl)-3,5-dinitrobenzamide, a new semisynthetic derivative from the Mangrove-associated actinomycete Pseudonocardia endophytica VUK-10. 3 Biotech (2016) 6:158.

 

 

 

Received on 28.06.2017             Modified on 18.07.2017

Accepted on 24.08.2017           © RJPT All right reserved

Research J. Pharm. and Tech 2018; 11(6): 2634-2640.

DOI: 10.5958/0974-360X.2018.00489.4