Chemical diversity, anti-inflamimmatory and anti-cancer activities of secondary metabolites in soft corals from Tun Sakaran Marine Park, Sabah

Soft corals (Cnidaria, Anthozoa, Octocorallia) are prolific producers of bioactive cembranoid diterpenes and steroids. North Borneon waters of Malaysia are rich with diverse species of soft corals but few have been investigated and documented. Present investigation delves upon the chemical consti...

Full description

Saved in:

Bibliographic Details
Main Author:	Intan Irna Zanil
Format:	Thesis
Language:	English
Published:	2015
Subjects:	QL Zoology
Online Access:	https://eprints.ums.edu.my/id/eprint/18928/1/Chemical%20diversity%2C%20anti-inflamimmatory.pdf
Tags:	Add Tag No Tags, Be the first to tag this record!

id	my-ums-ep.18928
record_format	uketd_dc
spelling	my-ums-ep.189282018-02-27T08:07:52Z Chemical diversity, anti-inflamimmatory and anti-cancer activities of secondary metabolites in soft corals from Tun Sakaran Marine Park, Sabah 2015 Intan Irna Zanil QL Zoology Soft corals (Cnidaria, Anthozoa, Octocorallia) are prolific producers of bioactive cembranoid diterpenes and steroids. North Borneon waters of Malaysia are rich with diverse species of soft corals but few have been investigated and documented. Present investigation delves upon the chemical constituents of three soft corals; Sinularia spp., Lobophytum spp. and Sarcophyton spp. from Tun Sakaran Marine Park (Sabah, Malaysia). Crude hexane and 90 % MeOH extracts were obtained and subjected to Thin Layer Chromatography (TLC) and High Performance Liquid Chromatography (HPLC) profiling. Secondary metabolites were isolated based on the chemical profiles and purified using repetitive Preparative Thick Layer Chromatography (PTLC). As a result, a total of eight diterpenes were isolated and their structures determined via spectroscopic techniques. Briefly, Sarcophyton spp. produced two iso-propyl(ene) type cembrane diterpenes; 1R, 4R, 2E, 7E, 11E)-cembra- 2,7,11-trien-4-ol (7) (5.8%) and 8 (2.5%). Additionally, Sinularia spp. produced (E, E, E)-6,10,14-trimethyl-3-methylene-cis-3a, 4,5,8,9,12,13,15-octahydrocyclotetradeca[ b]furan-2(3H)-one (1) (16.7%), 2 (5.0 %), denticulatolide (3) (4.5%) and 4 (4.5%) while Lobophytum spp. produced cembranolide A (5) (7.26%) and (9E,1 3E)-5-acetoxy-6-acetyl-9,13-dimethyl-3-methylene-34,3,5a,,6 ,12,8,1,12,14adecahydro- 2H-cyclotetrideca-(b)furan-2-o(n6e) (16.2%). These six compounds are cembranoid diterpenes containing a-methylene y lactones functional group. Of the eight compounds, 2,4 and 8 were identified as new compounds while the remaining five compounds are known. Compounds were tested for biological activities using cell based assays; 1) anti-inflammation (LPS-stimulated RAW 264.7 macrophage), and 2) anti-cancer (human promyelocytic leukemia cells - HL-60). Cembrane diterpenoids with lactone functionality showed potent activities against both cell based assays. At the concentration of 12.5 and 25.0 μg/ml, compound 3, 4,5 and 6 were found to significantly inhibit the production of nitric oxide (NO), IL-1ß and IL-6 by suppressing the production of iNOS protein in the LPS-stimulated RAW 264.7 macrophage. In addition, these compounds also mildly inhibited PGEZ production at the same concentration by blocking the accumulation of COX-2 protein in the cells. On the other hand, at the same concentration, compound 1 and 2 showed weak activity when tested against the LPS-stimulated RAW 264.7 macrophage. At the concentration of 25 μg/ml, an MTT assay showed that compound 3,4 and 6 exhibited potent cytotoxic activity against HL-60 cancer cells, while compound 1,2 and 5 are weakly cytotoxic against the same cell line. Furthermore, as the cancer cells were treated with the increasing concentration of compound 3,4 and 6 (12.5,25,50 μg/ml), the expression level of Bax and cleaved caspase-3w ere increased while the expression level of BCI-xl were decreased. Thus, it showed that these compounds also give apoptosis-induced effects on the cancer cells. This investigation is a new study on the chemical diversity and biology potential of soft corals in Tun Sakaran Marine Park. 2015 Thesis https://eprints.ums.edu.my/id/eprint/18928/ https://eprints.ums.edu.my/id/eprint/18928/1/Chemical%20diversity%2C%20anti-inflamimmatory.pdf text en public masters Universiti Malaysia Sabah Institute for Tropical Biology and Conservation
institution	Universiti Malaysia Sabah
collection	UMS Institutional Repository
language	English
topic	QL Zoology
spellingShingle	QL Zoology Intan Irna Zanil Chemical diversity, anti-inflamimmatory and anti-cancer activities of secondary metabolites in soft corals from Tun Sakaran Marine Park, Sabah
description	Soft corals (Cnidaria, Anthozoa, Octocorallia) are prolific producers of bioactive cembranoid diterpenes and steroids. North Borneon waters of Malaysia are rich with diverse species of soft corals but few have been investigated and documented. Present investigation delves upon the chemical constituents of three soft corals; Sinularia spp., Lobophytum spp. and Sarcophyton spp. from Tun Sakaran Marine Park (Sabah, Malaysia). Crude hexane and 90 % MeOH extracts were obtained and subjected to Thin Layer Chromatography (TLC) and High Performance Liquid Chromatography (HPLC) profiling. Secondary metabolites were isolated based on the chemical profiles and purified using repetitive Preparative Thick Layer Chromatography (PTLC). As a result, a total of eight diterpenes were isolated and their structures determined via spectroscopic techniques. Briefly, Sarcophyton spp. produced two iso-propyl(ene) type cembrane diterpenes; 1R, 4R, 2E, 7E, 11E)-cembra- 2,7,11-trien-4-ol (7) (5.8%) and 8 (2.5%). Additionally, Sinularia spp. produced (E, E, E)-6,10,14-trimethyl-3-methylene-cis-3a, 4,5,8,9,12,13,15-octahydrocyclotetradeca[ b]furan-2(3H)-one (1) (16.7%), 2 (5.0 %), denticulatolide (3) (4.5%) and 4 (4.5%) while Lobophytum spp. produced cembranolide A (5) (7.26%) and (9E,1 3E)-5-acetoxy-6-acetyl-9,13-dimethyl-3-methylene-34,3,5a,,6 ,12,8,1,12,14adecahydro- 2H-cyclotetrideca-(b)furan-2-o(n6e) (16.2%). These six compounds are cembranoid diterpenes containing a-methylene y lactones functional group. Of the eight compounds, 2,4 and 8 were identified as new compounds while the remaining five compounds are known. Compounds were tested for biological activities using cell based assays; 1) anti-inflammation (LPS-stimulated RAW 264.7 macrophage), and 2) anti-cancer (human promyelocytic leukemia cells - HL-60). Cembrane diterpenoids with lactone functionality showed potent activities against both cell based assays. At the concentration of 12.5 and 25.0 μg/ml, compound 3, 4,5 and 6 were found to significantly inhibit the production of nitric oxide (NO), IL-1ß and IL-6 by suppressing the production of iNOS protein in the LPS-stimulated RAW 264.7 macrophage. In addition, these compounds also mildly inhibited PGEZ production at the same concentration by blocking the accumulation of COX-2 protein in the cells. On the other hand, at the same concentration, compound 1 and 2 showed weak activity when tested against the LPS-stimulated RAW 264.7 macrophage. At the concentration of 25 μg/ml, an MTT assay showed that compound 3,4 and 6 exhibited potent cytotoxic activity against HL-60 cancer cells, while compound 1,2 and 5 are weakly cytotoxic against the same cell line. Furthermore, as the cancer cells were treated with the increasing concentration of compound 3,4 and 6 (12.5,25,50 μg/ml), the expression level of Bax and cleaved caspase-3w ere increased while the expression level of BCI-xl were decreased. Thus, it showed that these compounds also give apoptosis-induced effects on the cancer cells. This investigation is a new study on the chemical diversity and biology potential of soft corals in Tun Sakaran Marine Park.
format	Thesis
qualification_level	Master's degree
author	Intan Irna Zanil
author_facet	Intan Irna Zanil
author_sort	Intan Irna Zanil
title	Chemical diversity, anti-inflamimmatory and anti-cancer activities of secondary metabolites in soft corals from Tun Sakaran Marine Park, Sabah
title_short	Chemical diversity, anti-inflamimmatory and anti-cancer activities of secondary metabolites in soft corals from Tun Sakaran Marine Park, Sabah
title_full	Chemical diversity, anti-inflamimmatory and anti-cancer activities of secondary metabolites in soft corals from Tun Sakaran Marine Park, Sabah
title_fullStr	Chemical diversity, anti-inflamimmatory and anti-cancer activities of secondary metabolites in soft corals from Tun Sakaran Marine Park, Sabah
title_full_unstemmed	Chemical diversity, anti-inflamimmatory and anti-cancer activities of secondary metabolites in soft corals from Tun Sakaran Marine Park, Sabah
title_sort	chemical diversity, anti-inflamimmatory and anti-cancer activities of secondary metabolites in soft corals from tun sakaran marine park, sabah
granting_institution	Universiti Malaysia Sabah
granting_department	Institute for Tropical Biology and Conservation
publishDate	2015
url	https://eprints.ums.edu.my/id/eprint/18928/1/Chemical%20diversity%2C%20anti-inflamimmatory.pdf
_version_	1747836498581913600

Chemical diversity, anti-inflamimmatory and anti-cancer activities of secondary metabolites in soft corals from Tun Sakaran Marine Park, Sabah

Similar Items