faculty of resource science and technology studies and biological...faculty of resource science and...

Faculty of Resource Science and Technology

CHEMICAL STUDIES AND BIOLOGICAL ACTIVITIES OF

GONIOTHALAMUS TAPIS MIQ AND GONIOTHALAMUS VELUTINUS

AIRY SHAW

Nabihah Hamdan

Master of Science

(Natural Product Chemistry)

2014

ii

CHEMICAL STUDIES AND BIOLOGICAL ACTIVITIES OF GONIOTHALAMUS

TAPIS MIQ AND GONIOTHALAMUS VELUTINUS AIRY SHAW

Nabihah Hamdan

A thesis submitted

in fulfillment of the requirement for the Degree of

Master of Science

(Natural Product Chemistry)

Department of Chemistry


UNIVERSITI MALAYSIA SARAWAK

2014

i

DECLARATION

No portion of the work referred in this dissertation has been submitted in support of an

application for another degree of qualification of this or any other university or institution of

higher learning.

NABIHAH HAMDAN

Department of Chemistry


Universiti Malaysia Sarawak.

ii

ACKNOWLEDGEMENTS

Alhamdulillah, thank you to Allah for giving me the strength and patient in completing this

research and thesis. Foremost, I would like to express my sincere gratitude to my supervisor,

Professor Dr. Fasihuddin Badruddin Ahmad for his supervision, full support, guidance and

encouragement throughout my research and thesis writing. I am deeply grateful to Universiti

Malaysia Sarawak, UNIMAS for providing financial support (Zamalah). I take this

opportunity to express my grateful to the staff of Faculty of Resource Science and

Technology especially Mdm. Leida Anthony, Mdm. Norhayati Bujang and Mr. Benedict

Samling for their help in providing chemicals and apparatus and also technical assistance in

conducting and handling instruments.

I would like to express my great appreciation to my colleagues especially Ms Irna Syairina

Sahari, Mr. Mohd. Alhafiizh Zailani, Mdm. Fouziah Alet, Ms. Norihan Sam, Ms. Christine

Jinang, Ms. Aina Nabilla Bandah, Mdm. Nuraqilah Othman and Mr. Reagan Entigu Ak

Linton @ Jerah for their constants help, kindness, ideas, motivation, support and technical

assistance in conducting bioassays. I am indebted to Ms. Kathleen Michelle Mikal (Virology

Laboratory) for the help in providing bacteria for antibacterial screening. Special thank goes

to special pals, Dinh Thi Thanh Hong and Romeo Miranda III who have continuously giving

moral support and encouragement to finish this research. My deepest thanks to my family

especially my parent for their love, prayers, full support and patient throughout my life.

Lastly, I would like to thank to all the people who indirectly helped me in completing this

research and thesis.

iii

Chemical Studies and Biological Activities of Goniothalamus tapis Miq and

Goniothalamus velutinus Airy Shaw

Nabihah Hamdan

ABSTRACT

Chemical studies and biological activities were performed on Goniothalamus tapis Miq and

G. velutinus Airy Shaw. Methanolic extracts were partitioned using solvents with increasing

polarity to give hexane, dichloromethane, ethyl acetate and methanol partitions. Purification

through extensive column chromatography, preparative thin layer chromatography and

recrystallization resulted in the isolation and characterization of 5-hydroxy-3-amino-2-aceto-

1,4-napthoquinone and 9-deoxygoniopypyrone from G. tapis, while goniothalamin,

aristolactam AII, velutinam and 5,7-dihydroxyflavone were characterized from G. velutinus.

Structures of all pure compounds were elucidated based on their spectroscopic data especially

mass spectrometry, infrared, nuclear magnetic resonance and comparison with published

information. Biological activities screening (antibacterial, antioxidant, brine shrimp toxicity

and termiticidal) were performed on all partitions of G. tapis and G. velutinus (bark and root).

All G. tapis partitions showed weak antibacterial activities against Bacillus megaterium,

Lysteria monocytogenes, Escherichia coli and Salmonella entrica with inhibition zone in the

range of 7.2 to 9.7 mm. Ethyl acetate (GTEt) and methanol (GTM) partitions of G. tapis

showed strong ability to scavenge DPPH free radicals with EC50 74.5 and 86.0 ppm,

respectively and comparable to positive control, butylated hydroxyl toluene with EC50 of

110.1 ppm. 9-Deoxygoniopypyrone, goniothalamin and 5,7-dihydroxyflavone showed weak

antioxidant activity with EC50 more than 150.0 ppm. Dichloromethane partitions of G. tapis

and G. velutinus barks (GTD and GVBD) exhibited strong toxicity against brine shrimp,

Artemia salina with LC50 of 38.2 and 45.1 ppm, respectively and comparable with thymol

which was used as positive control with LC50 of 37.5 ppm. Ethyl acetate partition of G. tapis

(GTEt) and dichloromethane partition of G. velutinus (GVBD) showed potent termiticidal

activity against Coptotermes sp. with 100% mortality at concentration of 10% on the third day

of observation. GTEt and GVBD partitions exhibited strongest termiticidal activities with

LC50 of 0.04 and 0.06%, respectively.

Keywords: Goniothalamus tapis, G. velutinus, 5-hydroxy-3-amino-2-aceto-1,4-

napthoquinone, aristolactam AII, biological activities

iv

Kajian Kimia dan Aktiviti Biologi ke atas Goniothalamus tapis Miq dan Goniothalamus

velutinus Airy Shaw

Nabihah Hamdan

ABSTRAK

Kajian kimia dan aktiviti biologi telah dijalankan ke atas Goniothalamus tapis Miq dan G.

velutinus Airy Shaw. Ekstrak metanol telah dipartisikan menggunakan pelarut dengan

pertambahan kekutuban untuk memberikan partisi heksana, diklorometana, etil asetat dan

metanol. Penulenan melalui pemfraksian berulang, kromatografi lapisan nipis persediaan dan

kaedah penghabluran berjaya memisahkan dan mencirikan 5-hidroksi-3-amino-2-aseto-1,4-

naftokuinon dan 9-deoksigoniopipiron dari G. tapis, dan goniothalamin, aristolaktam AII,

velutinam dan 5,7-dihidroksiflavon dari G. velutinus. Pengecaman struktur bagi semua

sebatian tulen adalah berdasarkan maklumat-maklumat spektroskopi khususnya spektrometri

jisim, inframerah, resonan magnetik nuklear dan perbandingan dengan maklumat yang telah

diterbitkan. Pengujian aktiviti biologi (antibakteria, antioksida, ketoksikan larva udang dan

termitisidal) telah dijalankan ke atas kesemua partisi G. tapis dan G. velutinus (kulit dan

akar). Partisi-partisi G. tapis menunjukkan aktiviti antibakteria yang lemah terhadap Bacillus

megaterium, Lysteria monocytogenes, Escherichia coli dan Salmonella entrica dengan julat

perencatan antara 7.2 hingga 9.7 mm. Partisi etil asetat G. tapis (GTEt) dan metanol G. tapis

(GTM) menunjukkan keupayaan yang kuat dalam memerangkap radikal bebas DPPH, dengan

nilai EC50 74.5 dan 86.0 ppm, masing-masingnya dan setanding dengan kawalan positif iaitu

hidroksi toluena tertbutil dengan nilai EC50 110.1 ppm. 9-Deoksigoniopipiron, goniothalamin

dan 5,7-dihidroksiflavon menunjukkan aktiviti antioksida yang lemah dengan EC50 lebih

daripada 150.0 ppm. Partisi diklorometana (GTD dan GVBD) telah mempamerkan aktiviti

ketoksikan yang kuat terhadap larva udang, Artemia salina dengan LC50 38.2 dan 45.1 ppm,

masing-masingnya dan setanding dengan timol yang digunakan sebagai kawalan positif

dengan nilai LC50 37.5 ppm. Partisi etil asetat G. tapis (GTEt) dan partisi diklorometana G.

velutinus (GVBD) menunjukkan potensi dalam aktiviti termitisidal terhadap Coptotermes sp.

dengan 100% kematian pada kepekatan 10% pada hari ketiga. Partisi GTEt dan GVBD

mempamerkan aktiviti termitisidal yang kuat dengan nilai LC50 0.04 dan 0.06%, masing-

masingnya.

Kata kunci: Goniothalamus tapis, G. velutinus, 5-hidroksi-3-amino-2-aseto-1,4-naftokuinon,

aristolaktam AII, aktiviti biologi

v

TABLE OF CONTENTS

DECLARATION i

ACKNOWLEDGEMENTS ii

ABSTRACT/ABSTRAK iii

TABLE OF CONTENTS v

LIST OF ABBREVIATIONS ix

LIST OF TABLES xi

LIST OF FIGURES xiii

CHAPTER ONE: INTRODUCTION

1.1 General Introduction 1

1.2 Objectives 2

CHAPTER TWO: LITERATURE REVIEW

2.1 Annonaceae 3

2.1.1 Secondary Metabolites 4

2.1.2 Biological Activities 10

2.2 Goniothalamus spp. 12

2.2.1 Secondary Metabolites 13

2.2.1.1 Acetogenins 14

2.2.1.2 Styryllactones 19

2.2.1.3 Alkaloids 25

2.2.1.4 Flavonoids 31

2.2.1.5 Other Compounds 33

2.2.2 Uses and Biological Activities 36

2.3 Goniothalamus tapis Miq 40

2.4 Goniothalamus velutinus Airy Shaw 44

vi

CHAPTER THREE: MATERIALS AND METHODS

3.1 General Experimental Procedure 47

3.2 Plant Materials 48

3.3 Extraction Procedure 48

3.3.1 Liquid-liquid Extraction 48

3.4 Fractionation of Crude Extract 49

3.4.1 Thin Layer Chromatography 49

3.4.2 Visualization Agent

3.4.2.1 Vanillin Dipping (vanillin-sulphuric acid reagent) 50

3.4.2.2 Iodine Vapor Test 50

3.4.3 Column Chromatography 50

3.5 Preparative Thin Layer Chromatography 51

3.6 Recrystallization 51

3.7 Melting Point Determination 52

3.8 Structure Elucidation 52

3.8.1 Infrared Analysis

3.8.1.1 Solid Sample 52

3.8.1.2 Liquid Sample 53

3.8.2 Gas Chromatography-Mass Spectrometry Analysis 53

3.8.3 Nuclear Magnetic Resonance Analysis 54

3.9 Biological Activity Testing

3.9.1Antibacterial Screening 54

3.9.2 DPPH Free Radical Scavenging Assay 55

3.9.3 Brine Shrimp Toxicity Test 56

3.9.4 Termiticidal Activity Test 57

CHAPTER FOUR: RESULTS AND DISCUSSION

4.1 Extraction

4.1.1 Solvent Extraction of G. tapis and G. velutinus 58

4.1.2 Fractionation of G. tapis and G. velutinus Extract 59

4.2 Fractionation and Purification

4.2.1 Fractionation of G. tapis Dichloromethane Partition 60

vii

4.2.1.1 Purification of GTD-13-4-3 63

4.2.2 Fractionation of G. tapis Methanol Partition 64

4.2.2.1 Purification of GTM-9 66

4.2.3 Isolation and Purification of G. velutinus Hexane Extract 67

4.2.4 Fractionation of G. velutinus Bark Dichloromethane Partition 68

4.2.4.1 Purification of GVBD-12-0 69

4.2.4.2 Purification of GVBD-14 70

4.2.5 Fractionation of G. velutinus Root Methanol Partition 72

4.2.5.1 Purification of GVRM-9-4 74

4.3 Structure Elucidation

4.3.1 Compound 1 (GTD-13-4-3)

4.3.1.1 Infrared Spectrum 75

4.3.1.2 Mass Spectrum 77

4.3.1.3 NMR Spectra 79

4.3.2 Compound 2 (GTM-9)




4.3.3 Compound 3 (GVBH-0)




4.3.4 Compound 4 (GVBD-12-0)




4.3.5 Compound 5 (GVBD-14-3)




4.3.6 Compound 6 (GVRM-9-4-2)


viii



4.4 Spectroscopy Data of Pure Compounds Isolated from G. tapis and

G. velutinus 129

4.5 Biological Activity Testing

4.5.1 Antibacterial Screening 132

4.5.2 DPPH Free Radical Scavenging Assay 134

4.5.3 Brine Shrimp Toxicity Test 137

4.5.4 Termiticidal Activity Screening 139

CHAPTER FIVE: CONCLUSIONS AND SUGGESTIONS 143

REFERENCES 145

ix

LIST OF ABBREVIATIONS

3AO ovarian carcinoma cell

3PS in vivo mouse leukemia cell

9 KB nasopharynx carcinoma cell

A-549 lung carcinoma cell

AA arachidonic acid

Abs absorbance

ASW artificial saline water

Bel 7402 hepatoma cell

BHA butylated hydroxy anisole

BHT butylated hydroxy toluene

CEMC7 lymphoid cell

CDCl3 deuterated chloroform

COR-L23 large cell lung carcinoma

DEPT Distortionless Enhancement by Polarization Transfer

DMSO-d6 deuterated dimethyl sulfoxide

DPPH 2,2-diphenyl-1-picrylhydrazyl

EC50 Effective Concentration 50%

EI Electron Impact Ionization

GC-MS Gas Chromatography-Mass Spectrometry

HeLa cervical cancer cell

HepG2 liver hepatocellular cell

HGC-27 gastric carcinoma cell

HL-60 promyelocytic leukemia cell

HT-29 colon adenocarcinoma cell

IC50 Inhibitory Concentration 50%

IR Infrared

L1210 mouse leukemia cell

LC50 Lethal Concentration 50%

LD50 Lethal Dose 50%

LoVo colon adenocarcinoma cell

x

LS-174T colon cancer cell

KB mouth epidermal carcinoma cell

MCF-7 breast cancer cell

MDR multidrug resistant

MIC minimum inhibition concentration

NCI-H187 small cell lung carcinoma

NIST National Institute of Standards and Technology

NMR Nuclear Magnetic Resonance

P388 mouse lymphocytic leukemia cell

PACA-2 pancreatic cell

PAF platelet activating factor

PANC-1 pancreatic carcinoma cell

RPMI nasal epithelial cell

SGC-7901 stomach cancer cell

TE671 rhabdomyosarcoma cell

xi

LIST OF TABLES

Table 2.1 Uses and biological activities of some selected species in the

Annonaceae family 11

Table 2.2 Uses and biological activities of Goniothalamus spp. 37

Table 4.1 Mass and percentage yield of crude extracts 58

Table 4.2 Partitions mass and percentage yields 59

Table 4.3 Colour and mass of dichloromethane combined fractions of G. tapis 61

Table 4.4 Retention factor and colour of spots of GTD-13 obtained from G. tapis 61

Table 4.5 Colour and mass of combined fraction of GTD-13 from G. tapis 62

Table 4.6 Colour and mass of combined fraction of GTD-13-4 62

Table 4.7 Retention factor and colour of spots of GTD-13-4-3 63

Table 4.8 Colour and mass for each combined fractions of GTM of G. tapis 65

Table 4.9 Colour and mass of combined fraction of GTM-9 65

Table 4.10 Colour and mass of combined fractions of GVBD 68

Table 4.11 Solvent system, retention factor and colour of spots for GVBD-12-0

and GVBD-14 69

Table 4.12 Colour and mass of combined fraction of GVBD-14 71

Table 4.13 Colour and mass of combined fraction of GVRM 72

Table 4.14 Retention factor and colour of spots of GVRM-9 73

Table 4.15 Colour and mass of combined fraction of GVRM-9 73

Table 4.16 Physical properties, colour and mass of GVRM-9-4 bands 74

Table 4.17 Comparison of 1H and

13C NMR data for Compound 1 with 5-hydroxy-

3-amino-2-aceto-1,4-napthoquinone (147) (Soonthornchareonnon

et al., 1999) 83


13C NMR spectral data for Compound 2 with

9-deoxygoniopypyrone (58) (Fang et al., 1991) 92


13C NMR data for Compound 3 with

goniothalamin (45) (Wattanapiromsakul et al., 2005) 100


13C NMR data for Compound 4 with

aristolactam AII (88) (Tsuruta et al., 2002) 109


13C NMR of Compound 5 with velutinam (92)

xii

(Omar et al., 1992) 118


13C NMR of Compound 6 with

5,7-dihydroxyflavone (148) (Wagner & Chari, 1976) 127

Table 4.23 Antibacterial activity of partitions of G. tapis against Gram positive

and Gram negative bacteria 133

Table 4.24 DPPH free radical scavenging activity (%) of some G. tapis and G.

velutinus partitions and pure compounds at different concentrations and

their E50 values 135

Table 4.25 Percentage death of A. salina as a function of concentration of partition

from G. tapis and G. velutinus 138

Table 4.26 Termiticidal activities of partitions from G. tapis and G. velutinus

against Coptotermes sp. and their LC50 values on the third day 140

xiii

LIST OF FIGURES

Figure 2.1 Leaves and fruit of G. tapis Miq (Shaari, 2001) 41

Figure 2.2 Leaves and fruit of G. velutinus Airy Shaw (Shaari, 2001) 44

Figure 3.1 Protocol for termites’ toxicity test 57

Figure 4.1 Gas chromatogram of GTD-13-4-3 (Compound 1) isolated from G. tapis 64

Figure 4.2 Gas chromatogram of GTM-9 (Compound 2) isolated from G. tapis 66

Figure 4.3 Gas chromatogram of GVBH-0 (Compound 3) isolated from G. velutinus 67

Figure 4.4 Gas chromatogram of GVBD-12-0 (Compound 4) isolated from G.

velutinus (bark) 70

Figure 4.5 Gas chromatogram of GVBD-14-3 (Compound 5) isolated from G.

velutinus (bark) 71

Figure 4.6 Gas chromatogram of GVRM-9-4-2 (Compound 6) isolated from G.

velutinus (root) 75

Figure 4.7 IR spectrum of Compound 1 76

Figure 4.8 Mass spectrum of Compound 1 77

Figure 4.9 Proposed fragmentation patterns for Compound 1 78

Figure 4.10 1H NMR spectrum of Compound 1 in CDCl3 (500 MHz) 80

Figure 4.11 13

C NMR spectrum of Compound 1 in CDCl3 (125 MHz) 81

Figure 4.12 13

C DEPT spectrum of Compound 1 in CDCl3 (125 MHz) 82



Figure 4.15 Proposed fragmentation patterns for Compound 2 87

Figure 4.16 1H NMR spectrum of Compound 2 in DMSO-d6 (500 MHz) 89

Figure 4.17 13

C NMR spectrum of Compound 2 in DMSO-d6 (125 MHz) 90

Figure 4.18 13

C DEPT spectrum of Compound 2 in DMSO-d6 (125 MHz) 91



Figure 4.21 Proposed fragmentation patterns of Compound 3 96

Figure 4.22 1H NMR spectrum of Compound 3 in CDCl3 (500 MHz) 98

Figure 4.23 13

C NMR spectrum of Compound 3 in CDCl3 (125 MHz) 99


xiv


Figure 4.26 Purposed fragmentation patterns of Compound 4 104


Figure 4.28 13


Figure 4.29 13






Figure 4.34 13


Figure 4.35 13






Figure 4.40 13


Figure 4.41 13


Figure 4.42 Average % DPPH free radical scavenging activity of G. tapis

and G. velutinus partitions against concentration 136

Figure 4.43 Percentage death of Artemia salina as a function of concentration for

partitions of G. tapis and G. velutinus 139

Figure 4.44 Percentage death of Coptotermes sp. as a function of concentration of

partitions from G. tapis and G. velutinus after three days of observation 142

1

CHAPTER ONE

INTRODUCTION

1.1 General Introduction

Annonaceae family consists of 135 genera which include Annona, Duguetia, Goniothalamus,

Guatteria, Rollinia and Xylopia. Annonaceae family includes aromatic trees, shrubs or lianas

with at least 2500 species (Gottsberger et al., 2011) are distributed throughout subtropical and

tropical forest of America, Africa, Asia and Australia (Andrade et al., 2004). Members of this

family have diverse economical importance including horticultural for edible fruits,

production of soap, timber, perfumery and medicinal importance such as insecticide (Ming et

al., 1997), parasiticide (Bhakuni et al., 1972), analgesic (Nishiyama et al., 2006) and

antimalarial (Kamperdick et al., 2003; Andrade et al., 2004). Phytochemical studies on this

family afforded various types of secondary metabolites including essential oils, terpenes,

aromatic compounds, polyphenols, flavonoids, acetogenins, styryllactones and alkaloids

(Leboeuf et al., 1982; Andrade et al., 2004).

Goniothalamus is one of the largest genera in the Annonaceae family which consist of at least

164 species (The Plant List, 2010). This genus is well known for medicinal properties as

postpartum, abortifacient, antidote, insect repellant, also in treating fever, asthma,

rheumatism, headache, malaria, cholera, stomachache and skin diseases (Seidel et al., 2000;

Fasihuddin, 2004; Jantan et al., 2005a; Wiart, 2007; Moharam et al., 2010). Several classes of

secondary metabolites have been identified from this genus especially acetogenins, alkaloids,

azaanthraquinones, napthoquinones, styrylpyrones, benzenoids and styrene derivatives,

terpenoids, flavonoids and steroids (Limpipatwattana et al., 2008). The presence of notable

2

toxic compounds like acetogenins, styrylactones and aporphine alkaloids provide diverse

biological activities such as anticancer, antibacterial, antioxidant, larvicidal and pesticidal

(Alali et al., 1999; Jantan et al., 2005a; Abdul-Wahab et al., 2011; Jiang et al., 2011).

Present study focusing on the isolation of secondary metabolites and biological activities of

Goniothalamus tapis Miq and Goniothalamus velutinus Airy Shaw. Reports on chemical

compounds and biological activities of both species are limited which encouraged this study.

This study is important in order to add up the previous information and provide new scientific

knowledge for both species.

1.2 Objectives

The present study was carried out with the following objectives:

a) to extract and isolate secondary metabolites from G. tapis and G. velutinus.

b) to elucidate the structure of isolated compounds from G. tapis and G. velutinus using

various spectroscopic data.

c) to evaluate the biologically activities of partitions and pure compounds isolated from

G. tapis and G. velutinus especially antibacterial activity, antioxidant activity,

cytotoxicity against brine shrimp (Artemia salina) and termiticidal activity

(Captotermes sp.).

3

CHAPTER TWO

LITERATURE REVIEW

2.1 Annonaceae

Annonaceae is a large family of dicotyledonous flowering plants which regarded as among

the most primitive of extant angiosperms belongs to the order Magnoliales. Annonaceae

families are mesothermic and grow predominantly in lowland tropical regions. This family is

commonly consist of aromatic trees, shrubs or lianas (Gottsberger et al., 2011) which are

widespread throughout subtropical and tropical evergreen forest of America, Africa, Asia and

Australia (Andrade et al., 2004). This family comprised of at least 135 genera which include

Annona, Duguetia, Goniothalamus, Guatteria, Rollinia and Xylopia and about 2500 species

throughout the tropic (Gottsberger et al., 2011).

Members of this family has vast potential for economic value due to the horticultural demand

(Kundu, 2006) as the important source of edible fruits mostly in the genus of Annona

(Andrade et al., 2004) including the cherimoya (Annona cherimola), sweetsop (Annona

squamosa), soursop (Annona muricata), custard apple (Annona reticulata) and ilama (Annona

diversifolia), while Cananga and Rollinia genera have been cultured for similar purpose

(Leboeuf et al., 1982). Soap and edible oils can also be produced from the seed oils of this

family (Leboeuf et al., 1982). Wood of Annonaceae family was used as a source of

commercial timber (Ng, 1972; Kundu, 2006) and alcohol production (Leboeuf et al., 1982).

Flowers of some member in this family such as Oxandra lanceolata give aromatic oil which

is important for the perfumery industry (Leboeuf et al., 1982). Other than that, Annonaceae

family are also known for their importance in folk medicine for multiple purposes such as

4

insecticide (Ming et al., 1997), parasiticide (Bhakuni et al., 1972), analgesic (Nishiyama et

al., 2006) and also used to treat malaria (Kamperdick et al., 2003; Andrade et al., 2004),

bronchitis (Hasan et al., 1982a; Ming et al., 1997) and dysentery (Hasan et al., 1982b; Cruz et

al., 2011).

2.1.1 Secondary Metabolites

Annonaceae are well known as sources of diverse bioactive chemical compounds. This family

has been reported to consist various classes of secondary metabolites which include essential

oils particularly monoterpenes such as α-pinene, β-pinene, limonene, myrcene and ocimene,

other classes of terpenes and terpenoids (mainly diterpenes), polyphenols, flavonoids,

acetogenins, styryllactones (restricted to the genus Goniothalamus) and alkaloids (mostly

isoquinoline derived structure) (Leboeuf et al., 1982; Andrade et al., 2004). Among the

chemical constituents of this family, the annonaceous acetogenins, styryllactones and

isoquinoline alkaloids are the most important group of compounds due to their versatile

biological activities such as antiinfective, antimicrobial, antimitotic, antiparasitic,

antiprotozoal, antitumor, cytotoxic, insecticidal and pesticidal (Mikolajczak et al., 1990;

Cortes et al., 1993; Zhao et al., 1995; Waechter et al., 1998). These groups of compounds are

highly cytotoxic towards several human cell lines and have shown antiproliferative activity,

anti-HIV, antileukemic, antimalarial, antimicrobial, antitumor, insect growth retarder and also

the ability to treat Parkinson disease (Bentley, 1992; Aminimoghadamfarouj et al., 2011;

Gupta et al., 2011; Fontes et al., 2013).

More than 250 bioactive acetogenins have been isolated so far from the Annonaceae,

predominantly from several genera especially Annona, Asimina, Rollinia, Uvaria and

5

Goniothalamus (Wang et al., 2000). Few species of Annona have been reported to possess

large numbers of annonaceous acetogenins for example annonacin (1), annoreticuin-9-one (2),

cis-annoreticuin (3), goniothalamicin (4), isoannoncacin (5) and sabadeline (6) isolated from

Annona muricata (Luna et al., 2006; Ragasa et al., 2012).

1

2

3

4

6

5

6

A tetrahydroxy with non-adjacent tetrahydrofuran rings of annonaceous acetogenin, sylvaticin

(7) was isolated from the fruit of Rollinia slyvatica which is highly toxic and showed strong

insecticidal activity (Mikolajczak et al., 1990). Asimicin (8) isolated from Asimina triloba

which is a bistetrahydrofuran acetogenin, showed a great pesticidal activity (Pomper et al.,

2009).

7

8

7

Most common alkaloids isolated from this family such as liriodenine (9), nornuciferin (10),

O-methylmoschatoline (11) and oxoanalobine (12) are isoquinoline type (Goulart et al., 1986;

Perez-Amador et al., 2004; Dutra et al., 2012). Annona squamosa and Guatteria sp. were

reported to contain several aporphine alkaloids which mostly known to be toxic including

corydine (13), anonaine (14), norcorydine (15), norisocorydine (16), isocorydine (17),

glaucine (18), nornantenine (19) and xylopine (20) (Bhakuni et al., 1972; Montenegro et al.,

2003).

9 10 11

12 13 14

H3CO

H3CO

H3CO

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

8

15 R1 = OH R2 = OCH3 17 R1 = OH R2 = H

16 R1 = OCH3 R2 = OH 18 R1 = H R2 = OCH3

19 20

Other compounds like flavonoids are also reported from members of Annonaceae family for

example alnustin (21), kaempferol (22), quercetin-3-O-β-galactoside (23), eriodictyol (24),

catechin (25) and tectochrysin (26) isolated from Annona dioica and Polyalthia cauliflora

(Vega et al., 2007; Ghani et al., 2011; Formagio et al., 2013).

21 22

H3CO

H3CO

OCH3

OCH3

OCH3

H3CO

R1

R2

H3CO

H3CO

H3CO

H3CO

R1

R2

faculty of resource science and technology studies and biological...faculty of resource science and...

Documents