Goniothalamus Species: A Source of Drugs for the Treatment of Cancers and Bacterial Infections?

Irrespective of the presence of cytotoxic acetogenins and styryl-lactones in the genus Goniothalamus, only 22 species in the genus Goniothalamus, out of 160 species (13.7%) have so far been investigated. In an effort to promote further research on the genus Goniothalamus which could represent a source of drugs for the treatment of cancers and bacterial infections, this work offers a broad analysis of current knowledge on Goniothalamus species. Therefore, it includes (i) taxonomy (ii) botanical description (iii) traditional medicinal uses and (iv) phytochemical and pharmacological studies. We discuss the molecular mechanisms of actions of acetogenins and styryl-lactones, with some emphasis on the possible involvement of protein kinase, Bax and TRAIL receptors in the cytotoxic effects of styryl-lactones. We also report (v) the growth inhibition of several nosocomial bacteria by Goniothalamus. scortechinii. The crude methanol extract of G. scortechinii showed a good and broad spectrum of antibacterial activity against both Gram-negative and Gram-positive bacteria

Alkaloids, styryl lactones, and acetogenin from the roots of Goniothalamus lanceolatus Miq. and their antiproliferative activity / Nurulfazlina Edayah Rasol

Goniothalamus lanceolatus Miq., locally known as selukai or getimang is an ethnomedicinal plant indigenous to Sarawak. It is used traditionally to treat cancer. Phytochemical investigation on the roots of G. lanceolatus Miq. was conducted with the objective of comprehensively analyse the chemical constituents present in the roots of G lanceolatus, especially the ones potentially active as antiproliferative agents. The roots of G lanceolatus Miq. was extracted successively using hexane, dichloromethane, and methanol. The hexane and dichloromethane extracts showed antiproliferative activity against colorectal and lung cancer cell lines with percentage viability of cell less than 15%. Among the two extracts, the HPLC-DAD profile of the dichloromethane extract revealed the presence of more active UV components, and thus selected for further investigation. Mass-based dereplication strategy using inhouse and online mass database system successfully identified 24 constituents comprising of styryl lactones, alkaloids, and acetogenins in the dichloromethane extract. Isolation and purification from the active antiproliferative fractions, M2 to M7 led to characterization often styryl lactones, five alkaloids, and one acetogenin, where six dereplicated compounds were verified. All the structures were elucidated using 1Dand 2D-NMR spectroscopy. Absolute configurations of the styryl lactones were established by ECD analysis through comparison of the experimental and theoretically calculated ECD spectra, while stereochemistry of the alkaloids were established using the single X-ray crystallography data. The known 5-goniothalamin and parvistone D, are reported for the first time from Goniothalamus genus. Two new styryl lactones 57?,6i?-5-hydroxy-6-styryltetrahydropyrane-2-one and goniolanceolatin E, and five new styryl lactone diastereomers, 5i?,6i?-5-acetylgoniothalamin, 5R,6R-5- hydroxygoniothalamin, goniofupyrone B, deoxygoniopypyrone B, and goniolanceolatin A, along with a known pyrano-pyrone, lS,5S,7R,8S,3-exo,7-endo- (+)-8-ep/-9-deoxygoniopypyrone are described. The 6S/IS- styryl lactones isolated in this work are new discoveries in Goniothalamus species. Biogenesis pathway of these 6S/IS styryl lactones are proposed. In addition, two new alkaloids, (-)- goniolanceolactam and 2-acetyl-3-amino-1,4-naphthoquinone were also identified along with the known alkaloids, 2-acetyl-3-amino-5-hydroxy-1,4-naphthoquinone, cleistopholine and liriodenine, and the acetogenin, annonacin. 5-Goniothalamin, (-)- goniolanceolactam and annonacin exhibited potential antiproliferative activity against all tested cancer cell lines with the IC50 values of less than 10.0 |uM. The alkaloids, 2- acetyl-3 -amino-1,4-naphthoquinone and 2-acetyl-3 -amino-5-hydroxy-1,4- naphthoquinone, as well as liriodenine demonstrated antiproliferative against HCT116, A549, and NCI-H23 cell lines with IC50 values ranging between 4.5 to 10.3 |uM. 5i?,6i?- 5-hydroxygoniothalamin showed selective activity against lung cancer cell lines, A549, and NCI-H1299, with the IC50 values of 8.0 and 8.9 \*M, respectively. Other styryl lactones exhibited only weak activity. All isolated compounds were non-toxic to normal cell lines except for annonacin

Asymmetric synthesis and anti-tumor properties of conformationally constrained analogues of (S)-and (R)-goniothalamin

Thesis (Master)--İzmir Institute of Technology, Chemistry, İzmir, 2008Includes bibliographical references (leaves: 60-62)Text in English; Abstract: Turkish and Englishxiii, 69 leavesNaturally isolated 5-substituted-a,B-unsaturated-.-lactones gained great attention of researchers due to their cytotoxic and anti-tumor properties. Styryl lactones are the most interesting members of this group of naturally available compounds. One of the well-known and important example for styryl lactone is goniothalamin, which shows cytotoxicity against variety of cancer cell lines. This cytotoxic property was shown to be selective for cancer cell lines with no significant cytotoxicity toward non-malignant cells. Recent structure activity relationship (SAR) studies on goniothalamin shows that R configuration on its stereogenic center, trans double bonded linker and Michael acceptor parts of the molecules are essential for its cytotoxic activity. In this study conformationally constrained analogues of (S)- and (R)-goniothalamin were synthesized. Syntheses were started with the catalytic asymmetric allylation of benzaldehyde, naphthaldehyde and quinaldehyde derivatives in the first step, then formed alcohols were acrylated with acryloyl chloride to yield the corresponding esters, in the last step, ring closing metathesis with Grubbs. catalyst yielded the target molecules. Meanwhile, in this study the synthesized 5-aryl-substituted-a,B-unsaturated-S-lactones were tested to determine their cytotoxicity against MCF-7, PC-3, DU-145 and LNCAP cancer cell lines

Chemical constituents and antimicrobial activity of Goniothalamus macrophyllus (Annonaceae) from Pasoh Forest Reserve, Malaysia

The essential oils from the twig and root of Goniothalamus macrophyllus were obtained by hydrodistillation and subjected to Gas Chromatography (GC-FID) and Gas Chromatography/Mass Spectrometry (GC-MS) using CBP-5 capillary column in order to determine their chemical composition. Both twig and root oils and four reference standard compounds (-pinene, linalool, geraniol and geranyl acetate) were evaluated for their antimicrobial properties against gram positive and gram negative bacteria, yeast and dermatophyte fungi using broth microdilution methods. The GCMS analysis revealed twenty-one and fourteen compounds from twig and root oils which represented 90.0 and 42.5% of the total oils, respectively. The oils were found to possess the following major components: twig: geranyl acetate (45.5%), geraniol (17.0%), linalool (12.7%) and camphene (7.5%); root: cyperene (9.8%), geranyl acetate (9.4%), geraniol (3.4%) and linalool (2.6%). Other components present in appreciable amounts in both essential oils were -pinene (0.8%) and benzaldehyde (0.5%). The root oil exhibited the most notable inhibitory activity (0.3 mg/ml) against Vancomycin intermediate-resistance Staphylococcus aureus (VISA 24), Staphylococcus epidermidis and Candida albicans. -pinene meanwhile inhibited the bacteria and fungal growth at 0.3 and 2.5 mg/ml. With regards to antimicrobial potential, -pinene superceeds linalool, geraniol and geranyl acetate, respectively.Keywords: Goniothalamus macrophyllus, Annonaceae, essential oils, geranyl acetate, cyperene, geraniol, linalool, -pinene, antimicrobial activityAfrican Journal of Biotechnology Vol. 9(34), pp. 5511-5515, 23 August, 201

Chemical constituents from the hexane fraction of Goniothalamus Macrophyllus roots / Norkamilah Mohammed @ Abdullah

Goniothalamus is one of the species from the Annonaceae family consisting of 115 species distributed throughout the tropics and subtropics. Goniothalamus macrophyllus is a medicinal plant used widely in Peninsular Malaysia and known by the local name “pokok gajah beranak”. Phytochemical studies on Goniothalamus species have led to the isolation and characterization of large number of styryl lactones, acetogenins, alkaloids and flavanoids. Besides, investigation on the biological activities of Goniothalamus species showed the potential usage as an anticancer, antimalarial, antiplasmodial and antimicrobial. The objectives of the study are to isolate compounds from the hexane fraction from the roots of G. macrophyllus and test against brine shrimp assay. Dried roots of G. macrophyllus were ground into fine powder using a cutter mill. The ground roots were soaked in 80 % aqueous methanol at room temperature, filtered and the solvent were removed under reduced pressure to give crude methanolic extract. The crude extract was further suspended in aqueous methanol and sequentially partitioned with «-hexane, chloroform and /7-butanol. Two known compounds, goniothalamin (13) and linderatone (147) with two new compounds, goniolandrene A (148) and B (149) were isolated and purified from the hexane fraction by using analytical HPLC, preparative HPLC and TLC preparative. The structures were discussed and confirmed by using one (ID) and two - dimensional (2D) NMR, MS-TOF, IR, UV-Vis spectroscopy and comparison with the known compounds. The isolated compounds were tested against Brine Shrimp Lethality assay (BSL)

Total synthesis of styryl-lactones and related compounds.

by Tsui Hon-chung.Thesis (M.Phil.)--Chinese University of Hong Kong, 1993.Includes bibliographical references (leaves 74-77).Abstract --- p.iAcknowledgements --- p.iiBiography --- p.iiiAbbreviations --- p.v-viChapter 1. --- IntroductionChapter 1.1 --- Styryl-lactones from Piper genus --- p.1-2Chapter 1.2 --- Styryl-lactones from Goniothalamus genus --- p.2-15Chapter 1.3 --- Biosynthetic pathways --- p.15-17Chapter 2. --- Results and discussionChapter 2.1 --- Goniofufurone: Synthesis and absolute configuration --- p.18-28Chapter 2.2 --- Synthesis of (+)-goniofufurone --- p.28-34Chapter 2.3 --- Synthesis of (+)-goniobutenolide A and (-)-goniobutenolide B --- p.34-37Chapter 2.4 --- Synthesis of (+)-goniopypyrone --- p.37-39Chapter 2.5 --- Synthesis of (+)-altholactone --- p.39-41Chapter 2.6 --- Synthesis of (+)-goniotriol and (+)-7-acetylgoniotriol --- p.41-44Chapter 3. --- Conclusions --- p.45-47Chapter 4. --- Experimental --- p.48-73Chapter 5. --- References --- p.74-77Chapter 6. --- List of spectra --- p.78"1H-NMR spectra of compounds 14，16, 20，21b, 22，26 and 27" --- p.79-8

Novel isosteres and bioisosteres of natural styryl lactones: design,synthesis and antiproliferative activity

U  radu  su  ostvarene  višefazne  sinteze  većeg  broja  analoga  prirodnih  stiril-laktona  (+)-goniofufurona  i  7-epi-(+)-goniofufurona  polazeći  iz  D-glukoze. Ispitana  je  in  vitro  citotoksičnost  sintetizovanih  analoga  prema  devet malignih  i  jednoj  zdravoj  ćelijskoj  liniji.  Uspostavljeni  su  korelacioni  odnosi izmedju  strukture  i  antiproliferati vne  aktivnosti  sintetizovanih  proizvoda, pored  toga  uradjeni  su  i  dodatni  biološki  testovi  koji  se  odnose  na dokazivanje  mehanizma  citotoksičnog  dejstva  pomenutih  stiril-laktona  i analoga.Multistep  synthesis  of   a  number  of  natural  styryl  lactones goniofufurone  and  7-epi-goniofufurone  analogues  was  achieved starting  f rom  D-glucose.  In  vitro  cytotoxicity  of  newly  synthetized analogues  against  nine  human  tumour  cell  lines  and  against  a single normal cell line was evaluated. Structure-activity relationships were  established  for  both  natural  products  and  analogues.  Some additional  biological  tests  related  to  the  cell mechanisms  underlying the  cytotoxicity  of   the  mentioned  styryl  lactones  and  analogues, were also carried out