Sumberdaya Farmasi

Kelautan
MARINE BIODIVERSITY AND THEIR
POTENTIAL FOR DEVELOPING
PHARMACEUTICAL AND COSMETICAL
INDUSTRY IN INDONESIA
 Marine Biodiversity Geotectonic Position

UNCLOS
Implementation

Dynamic Oceanography and International Sea

Climate Variability Lines
2
Sources • Coastal & marine organisms
used as traditional medicine
Banten, P. Seribu, Buton,
Lombok, Bali, Mentawai, Aceh,
Kalimantan, Bangka-Belitung,
Maluku (Kayoa, Jailolo)
• Marine algae, sponges, corals
 Banten, P. Seribu, Garut,
Sulawesi
• Symbiotic microorganisms of
coastal & marine organisms
• Thermophilic Microorganisms
from unique sources ( hot spring
bracksist +saline)
Sample collection
Traditional knowledge Screening for bioative compound (non-target & target/molecular)
Random Antiinfectives (antimicrobial)
Thermophilic microorganism Anticancer ( Cytotoxic, Topoisomerase inhibitor)
Antioxidant (anticholesterol & antiatherogenic, anticancer)
Other traditional usage (UV-protector, androgenic, etc)
Novel enzime
Crude extracts

Identification Selected organisms Bioassay guided

Morphological fractionation
Biochemical
Molecular
Symbiont isolation Purification &
structure elucidation

Formulation Bioprocess Culture

Nutraceuticals, cosmetics development development
Lead compound
Feed, others
 Table . Some of samples and their biological activities
No Group Bioactivity Scientific name
1 Coastal plant Antioxidant, natural color, cytotoxic Pandanus sp
2 Coastal plant Antimicrobes, antioxidant, biodesinfectant Pemphis sp
3 Coastal plant Antimicrobe & Antioxidant, cytotoxic Ipomoea sp
4 Sea star Antioxidant Astropecten sp
5 Sea worm aprodisiax Eunice sp
6 Sea cucumber Antimicrobes, cytotoxic Sticopus sp
7 Sea slug Antioxidant, aprodisiax Discodoris sp
8 Mangrove Antimicrobe, sunscreen, cytotoxic Xylocarpus sp
9 Fish antifouling Carcharhinus sp
10 Algae Antimicrobe Entheromorpha sp
11 Coastal plant Antimicrobe Clerodendrum
12 Algae Antioxidant Gelidiella sp
13 Coastal plant Antimicrobe, antioxidant, cytotoxic Solanum sp
14 Sponge cytotoxic Stylotella sp
15 Sponge cytotoxic Stylissia sp
16 Sponge cytotoxic Axinella sp
17 Sponge Cytotoxic Acanthella sp
18 Algae Cytotoxic unidentified
 Source Substance Activity Price
sponge Manoalide Phospolipase A2 inhibitor $ 120 / mg

sponge Calyculin A Protein phopatase inhibitor $ 105 / 25 mg

sponge Luffariellolide Phospolipase A2 inhibitor $ 100 / mg

sponge 12-epi- Phospolipase A2 inhibitor $ 136 / mg
scalaridial
sponge Latrunculin B Actin polymerization inhibitor $ 90 / mg

sponge Mycalolide B Actin polymerization inhibitor $ 212 / 20 µg

sponge Swinholide A Actin microfilament disruptor $ 100 / 20 µg

Dinoflagelata Okadaic acid Protein phospatase inhibitor $ 75 / 25 µg

Bryozoan Bryostatin 1 Protein kinase C activator $ 88 / 10 µg

BioMol [ www.biomol.com]
 RESULTS FROM THE ASSESSMENT OF BPPT
Secondary Metabolites from sponges
From Axinella carteri H2 N
H2N N
H 2N
N N
HN
HN O
HN O
O Br
Br
Br
HN
HN HN NH
NH NH
O O
O
3-Bromhymenialdisin Hymenialdisin
Debromhymenialdisin
•Insecticide •Insecticide •Insecticide
•Protein Phosphatase Inhibitor •Novel
1
3
NH
4 OCH3 Aaptamin
•Antibacterial
9
N
5
8 •Cytotoxic
6 7 OCH3

From Aaptos Suberitoides

7
Click toSecondary
edit Master
Metabolitestitle style
from sponges
From Theonella swinhoei
O
H3C
N

HO OH
CH3
P H3C CH3
O
O O
O NH2
CH3 CH3 CH3
OCH3
O

CH3 CH3 OH OH OCH3

Calyculin derivative
•Active against 51 cancer cell lines
•Insecticide
•Fungicide
•Protein phosphatase Inhibitor 2
•Novel
8
 Antimicrobes compound from marine algae Eucheuma serra,
Halimeda opuntia dan Hydroclathrus clathratus (Warambadi, Sumba)

1. Fatty acids

O OH

OH OH O

OH
8-Octadecenoic acid, methyl ester;
(E)-Methyl trans-8-octadecenoate

3-hydroxy-nonadeca-5,8,11,14-tetraenoic acid 3-hydroxy-20-methyl heneicosa-5,8,11-trienoic acid

 O
O
O
O
O
O

O
O

1,2- Benzenedicarboxylic acid, dioctyl ester 1,2- Benzenedicarboxylic acid, diisooctyl ester

O
O
O

Methyl eicosa-5,8,11,14,17-pentaenoate Methyl arachidonate

 O
O
O
O
O
O

O
O

1,2- Benzenedicarboxylic acid, dioctyl ester 1,2- Benzenedicarboxylic acid, diisooctyl ester

O
O
O

Methyl eicosa-5,8,11,14,17-pentaenoate Methyl arachidonate

 2. Steroids
I
O O
O
H
H

H H
H H

O O O

dihydrotestosteron acetic acid;

androstan-3-one,17-(acetyloxy)-,(5, 17)

H H
H H

HO

Preg-15-en-20-one,17-methyl Cholest-5-en-3β-ol, 24-propylidene

 O
O
O
O
O
O

O
O

1,2- Benzenedicarboxylic acid, dioctyl ester 1,2- Benzenedicarboxylic acid, diisooctyl ester

O
O
O

Methyl eicosa-5,8,11,14,17-pentaenoate
Methyl arachidonate
2. Steroids
I

O O
O
H
H

H H
H H

O O O

androstan-11-one,3-(acetyloxy)-17-iodo-(17)
dihydrotestosteron acetic acid;
androstan-3-one,17-(acetyloxy)-,(5, 17)

H H
H H

HO

Preg-15-en-20-one,17-methyl Cholest-5-en-3β-ol, 24-propylidene

3. Aldehydes
H

O OH

O
9-[3-(1-hydroxy-butyl)-oxiranyl]-nonanal

O OH

11-[3-(1-hydroxy-butyl)-oxiranyl]-undecanal

4. Ether

3,7,11-Trimethyl-1-(3-methyl-butoxy)-dodec-2-en
 SCREENING, ISOLATION AND IDENTIFICATION OF
TOPOISOMERASE INHIBITOR AS MOLECULAR
TARGET FOR ANTICANCER

• Cell based (cytotoxic)

• Target based (protein or
enzyme)
• Topoisomerases: essential
nuclear enzymes untuk DNA
replication.
– Topoisomerase I generates
single-stranded breaks,
– topoisomerase II introduces
double-stranded breaks.
• Topoisomerase inhibitors :
causing to cell death.
• All cell require topoisomerase,
however cancer cells need
more than normal cell
 Tabel 3. Topoisomerase Inhibitor Cancer Drugs

Target Indikasi Status Manufacturer

 Produk
Campto Topoisomerase I Colorectal cancer Market Aventis and Merck
Hycamtin Topoisomerase I Small cell lung cancer Market GlaxoSmithKline
Lucanthone Topoisomerase II Brain tumor Phase II SuperGen
MLN576 Topoisomerase I and II Various tumors Phase I Millennium
Novantrone Topoisomerase II Leukemia and non- Market OSI
small cell lung cancer
OSI211 Topoisomerase I Ovarian and mall cell Phase I OSI
lung cancers
Pegamotecan Topoisomerase I Gastroesopheagal Phase II Enzon
cancer
Rubitecan Topoisomerase I Colorectal cancer Phase II SuperGen