Styryllactones and bis-styryllactones from the stembark of goniothalamus lanceolatus miq. and their cytotoxic activity / Nur Vicky Bihud

In the search for new bioactive compounds from plant of Malaysia, Goniothalamus lanceolatus Miq., an indigenous plant from Sarawak was investigated. This plant is used by the natives as a traditional medicine to treat various illnesses such as cancer, fever and skin diseases. Preliminary cytotoxic s...

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Main Author:	Bihud, Nur Vicky
Format:	Thesis
Language:	English
Published:	2020
Subjects:	Physical and theoretical chemistry
Online Access:	https://ir.uitm.edu.my/id/eprint/35003/1/35003.pdf
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spelling	my-uitm-ir.350032022-03-29T04:48:32Z Styryllactones and bis-styryllactones from the stembark of goniothalamus lanceolatus miq. and their cytotoxic activity / Nur Vicky Bihud 2020-04 Bihud, Nur Vicky Physical and theoretical chemistry In the search for new bioactive compounds from plant of Malaysia, Goniothalamus lanceolatus Miq., an indigenous plant from Sarawak was investigated. This plant is used by the natives as a traditional medicine to treat various illnesses such as cancer, fever and skin diseases. Preliminary cytotoxic screening on the crude extracts against lung and colorectal cancer cell lines showed promising results from all parts with percentage of cell viability of less than 20% at concentration of 100 μg/mL. In view of the interesting ethno-medicinal and biological properties mentioned above, a detailed phytochemical study was conducted to provide scientific data for this plant. This study reported the isolation, structure elucidation, cytotoxic evaluation of pure compounds, and the plausible biogenetic route on the isolated compounds. The isolation and purification of compounds were accomplished by utilizing modern chromatographic techniques such as MPLC, HPLC and recycling HPLC. All structures were established through extensive 1D and 2D NMR analysis, whilst the absolute configurations were established by electronic circular dichroism data (ECD), supported by NOESY experiments and data comparison with literature values. Twelve styryllactones were isolated and identified as 6S-goniothalamin 1, (6S,7S,8S)- goniodiol 2, (6S,7R,8S)-8-chlorogoniodiol 3, (6S,7S,8S)-goniodiol-7-monoacetate 4, (6S,7S,8S)-goniodiol-8-monoacetate 5, (6S,7S,8S)-(-)-ent-isogoniothalamin oxide 6, (1S,5S,7R,8R)-3-endo, 7-endo-(-)-9-deoxygoniopypyrone 7, (1S,5S,7S,8R)-3-exo, 7- exo-(+)-deoxygoniopypyrone B 8, (1S,5S,7R,8S)-3-endo, 7-endo-(-)-8-epi-9- deoxygoniopypyrone 9, (1S,5S,7R,8S)-3-exo, 7-endo-(+)-8-epi-9- deoxygoniopypyrone 10, (1S,5S,7R,8S)-3-endo, 7-endo-(-)-8-epi-9- deoxygoniopypyrone acetate 11 and (1S,5S,7S,8S)-(-)-goniofupyrone B 12. Interestingly, the styryllactones isolated from this plant possessed an α,β-unsaturated δ-lactone moiety with a 6S configuration, and δ-lactone moiety with a 1S configuration, which were a rare occurrence from nature. With the exception of 10, all compounds are reported for the first time from the genus Goniothalamus. Seven new bis-styryllactones, named goniolanceolatins A-H 13-19 were also described. These goniolanceolatins comprised of either a pyranopyrone unit and a styrylpyrone unit, or two styrylpyrone units, which are linked by an ether bridge at positions C-8/C-8', C- 8/C-7', or C-7/C-8'. The new compounds 13-19 were evaluated for their cytotoxicity against series of human lung and colorectal cancer cell lines, which revealed a promising cytotoxicity for 14 and 16 with IC50 values ranging from 2.2 to 7.8 μM, while sparing the human non-cancerous lung and colorectal cells. Docking studies of the active compounds 14 and 16 showed that they were able to bind with EGFR tyrosine kinase and cyclin-dependent kinase 2 through hydrogen bonding interactions with the important amino acids such as Lys721, Met769, Asn818, Arg157, Ile10, and Glu12. 2020-04 Thesis https://ir.uitm.edu.my/id/eprint/35003/ https://ir.uitm.edu.my/id/eprint/35003/1/35003.pdf text en public phd doctoral Universiti Teknologi MARA Faculty of Applied Sciences Ismail, Nor Hadiani (Prof Dr)
institution	Universiti Teknologi MARA
collection	UiTM Institutional Repository
language	English
advisor	Ismail, Nor Hadiani (Prof Dr)
topic	Physical and theoretical chemistry
spellingShingle	Physical and theoretical chemistry Bihud, Nur Vicky Styryllactones and bis-styryllactones from the stembark of goniothalamus lanceolatus miq. and their cytotoxic activity / Nur Vicky Bihud
description	In the search for new bioactive compounds from plant of Malaysia, Goniothalamus lanceolatus Miq., an indigenous plant from Sarawak was investigated. This plant is used by the natives as a traditional medicine to treat various illnesses such as cancer, fever and skin diseases. Preliminary cytotoxic screening on the crude extracts against lung and colorectal cancer cell lines showed promising results from all parts with percentage of cell viability of less than 20% at concentration of 100 μg/mL. In view of the interesting ethno-medicinal and biological properties mentioned above, a detailed phytochemical study was conducted to provide scientific data for this plant. This study reported the isolation, structure elucidation, cytotoxic evaluation of pure compounds, and the plausible biogenetic route on the isolated compounds. The isolation and purification of compounds were accomplished by utilizing modern chromatographic techniques such as MPLC, HPLC and recycling HPLC. All structures were established through extensive 1D and 2D NMR analysis, whilst the absolute configurations were established by electronic circular dichroism data (ECD), supported by NOESY experiments and data comparison with literature values. Twelve styryllactones were isolated and identified as 6S-goniothalamin 1, (6S,7S,8S)- goniodiol 2, (6S,7R,8S)-8-chlorogoniodiol 3, (6S,7S,8S)-goniodiol-7-monoacetate 4, (6S,7S,8S)-goniodiol-8-monoacetate 5, (6S,7S,8S)-(-)-ent-isogoniothalamin oxide 6, (1S,5S,7R,8R)-3-endo, 7-endo-(-)-9-deoxygoniopypyrone 7, (1S,5S,7S,8R)-3-exo, 7- exo-(+)-deoxygoniopypyrone B 8, (1S,5S,7R,8S)-3-endo, 7-endo-(-)-8-epi-9- deoxygoniopypyrone 9, (1S,5S,7R,8S)-3-exo, 7-endo-(+)-8-epi-9- deoxygoniopypyrone 10, (1S,5S,7R,8S)-3-endo, 7-endo-(-)-8-epi-9- deoxygoniopypyrone acetate 11 and (1S,5S,7S,8S)-(-)-goniofupyrone B 12. Interestingly, the styryllactones isolated from this plant possessed an α,β-unsaturated δ-lactone moiety with a 6S configuration, and δ-lactone moiety with a 1S configuration, which were a rare occurrence from nature. With the exception of 10, all compounds are reported for the first time from the genus Goniothalamus. Seven new bis-styryllactones, named goniolanceolatins A-H 13-19 were also described. These goniolanceolatins comprised of either a pyranopyrone unit and a styrylpyrone unit, or two styrylpyrone units, which are linked by an ether bridge at positions C-8/C-8', C- 8/C-7', or C-7/C-8'. The new compounds 13-19 were evaluated for their cytotoxicity against series of human lung and colorectal cancer cell lines, which revealed a promising cytotoxicity for 14 and 16 with IC50 values ranging from 2.2 to 7.8 μM, while sparing the human non-cancerous lung and colorectal cells. Docking studies of the active compounds 14 and 16 showed that they were able to bind with EGFR tyrosine kinase and cyclin-dependent kinase 2 through hydrogen bonding interactions with the important amino acids such as Lys721, Met769, Asn818, Arg157, Ile10, and Glu12.
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Bihud, Nur Vicky
author_facet	Bihud, Nur Vicky
author_sort	Bihud, Nur Vicky
title	Styryllactones and bis-styryllactones from the stembark of goniothalamus lanceolatus miq. and their cytotoxic activity / Nur Vicky Bihud
title_short	Styryllactones and bis-styryllactones from the stembark of goniothalamus lanceolatus miq. and their cytotoxic activity / Nur Vicky Bihud
title_full	Styryllactones and bis-styryllactones from the stembark of goniothalamus lanceolatus miq. and their cytotoxic activity / Nur Vicky Bihud
title_fullStr	Styryllactones and bis-styryllactones from the stembark of goniothalamus lanceolatus miq. and their cytotoxic activity / Nur Vicky Bihud
title_full_unstemmed	Styryllactones and bis-styryllactones from the stembark of goniothalamus lanceolatus miq. and their cytotoxic activity / Nur Vicky Bihud
title_sort	styryllactones and bis-styryllactones from the stembark of goniothalamus lanceolatus miq. and their cytotoxic activity / nur vicky bihud
granting_institution	Universiti Teknologi MARA
granting_department	Faculty of Applied Sciences
publishDate	2020
url	https://ir.uitm.edu.my/id/eprint/35003/1/35003.pdf
_version_	1783734285217300480

Styryllactones and bis-styryllactones from the stembark of goniothalamus lanceolatus miq. and their cytotoxic activity / Nur Vicky Bihud

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