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Isolation and Characterization of Secondary Metabolites from the Aerial Parts of Homalium cochinchinensis Collected in Vietnam.
Record Type:
Electronic resources : Monograph/item
Title/Author:
Isolation and Characterization of Secondary Metabolites from the Aerial Parts of Homalium cochinchinensis Collected in Vietnam./
Author:
Addo, Ermias Mekuria.
Description:
1 online resource (270 pages)
Notes:
Source: Dissertations Abstracts International, Volume: 84-01, Section: B.
Contained By:
Dissertations Abstracts International84-01B.
Subject:
Pharmacology. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29310738click for full text (PQDT)
ISBN:
9798834019091
Isolation and Characterization of Secondary Metabolites from the Aerial Parts of Homalium cochinchinensis Collected in Vietnam.
Addo, Ermias Mekuria.
Isolation and Characterization of Secondary Metabolites from the Aerial Parts of Homalium cochinchinensis Collected in Vietnam.
- 1 online resource (270 pages)
Source: Dissertations Abstracts International, Volume: 84-01, Section: B.
Thesis (Ph.D.)--The Ohio State University, 2021.
Includes bibliographical references
Despite a general decline in terms of mortality rate, cancer remains a major health concern as it is the second-leading cause of death in the United States. Several effective treatment options are available or are being developed but these have met with some obstacles such as drug resistance and the severe side effects often displayed in chemotherapy. Thus, there is a continued need to develop safer, more efficacious and drug resistance-"proof" oncology drugs. With their long track record of success, natural products are viable options to provide not only new effective drugs but also pharmacological tools for laboratory use. This evident success of natural products forms the basis of the multi-institutional Program Project (P01 CA125066) awarded to Prof. A. Douglas Kinghorn (Principal Investigator) from the U.S. National Cancer Institute, National Institutes of Health. This collaborative project aims to discover anticancer drugs from tropical plants, freshwater and terrestrial cyanobacteria, filamentous fungi, and U.S. lichens and their mycobionts.Thus, as part of this program project, this dissertation work deals with the isolation and characterization of secondary metabolites from the aerial parts of Homalium cochinchinensis (Lour.) Druce collected in Vietnam. The methanol-soluble extract derived from this plant was found to be active in a mitochondrial transmembrane potential (MTP) inhibition assay (IC50 value of 14.8 µg/mL) despite being deemed inactive when evaluated against human HeLa cervical and DU-145 prostate cancer cell lines. Thus, the MTP inhibition assay was used, in part, to guide the isolation process using chromatographic methods (e.g., TLC and HPLC). Overall, this led to the isolation of eleven secondary metabolites belonging to the spermidine alkaloid (195 and 196), glycoside (131, 197 and 200-204), depsidone (198a) and phenol (199) natural product classes. Of these, compounds 195-197 and 200-204 were new, while compounds 131, 198a and 199 were already known. Hence, this dissertation work presents the structural elucidation of all of these compounds using various spectroscopic (1D- and 2D NMR, optical rotation, electronic circular dichroism, infrared, ultraviolet) and high-resolution mass spectrometry methods. In addition, selected compounds (i.e., those isolated in sufficient amounts) were tested against the MTP, NF-?B inhibition, and human cancer line cytotoxicity (HeLa, HT-29, PC-3, DU-145, MDA-MB-231, and MCF-7) assays.Even though these selected compounds from H. cochinchinensis were inactive in the above-mentioned assays, this dissertation work on the isolation and characterization of the new compounds obtained led to several important observations and conclusions. For example, alkaloids 195 and 196 belong to the rare subclass of spermidine alkaloids called dovyalicins and hence, their isolation from the title plant increases the members known of this class of uncommon natural products. Furthermore, as suggested by other investigators, the isolation of compounds 202-204 with a 2,5-dihydroxybenzyl alcohol unit corroborates the proposal to re-classify the genus Homalium from the plant family Flacourtiaceae (among others) to the Salicaceae sensu lato.
Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023
Mode of access: World Wide Web
ISBN: 9798834019091Subjects--Topical Terms:
634543
Pharmacology.
Subjects--Index Terms:
Secondary metabolitesIndex Terms--Genre/Form:
542853
Electronic books.
Isolation and Characterization of Secondary Metabolites from the Aerial Parts of Homalium cochinchinensis Collected in Vietnam.
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Despite a general decline in terms of mortality rate, cancer remains a major health concern as it is the second-leading cause of death in the United States. Several effective treatment options are available or are being developed but these have met with some obstacles such as drug resistance and the severe side effects often displayed in chemotherapy. Thus, there is a continued need to develop safer, more efficacious and drug resistance-"proof" oncology drugs. With their long track record of success, natural products are viable options to provide not only new effective drugs but also pharmacological tools for laboratory use. This evident success of natural products forms the basis of the multi-institutional Program Project (P01 CA125066) awarded to Prof. A. Douglas Kinghorn (Principal Investigator) from the U.S. National Cancer Institute, National Institutes of Health. This collaborative project aims to discover anticancer drugs from tropical plants, freshwater and terrestrial cyanobacteria, filamentous fungi, and U.S. lichens and their mycobionts.Thus, as part of this program project, this dissertation work deals with the isolation and characterization of secondary metabolites from the aerial parts of Homalium cochinchinensis (Lour.) Druce collected in Vietnam. The methanol-soluble extract derived from this plant was found to be active in a mitochondrial transmembrane potential (MTP) inhibition assay (IC50 value of 14.8 µg/mL) despite being deemed inactive when evaluated against human HeLa cervical and DU-145 prostate cancer cell lines. Thus, the MTP inhibition assay was used, in part, to guide the isolation process using chromatographic methods (e.g., TLC and HPLC). Overall, this led to the isolation of eleven secondary metabolites belonging to the spermidine alkaloid (195 and 196), glycoside (131, 197 and 200-204), depsidone (198a) and phenol (199) natural product classes. Of these, compounds 195-197 and 200-204 were new, while compounds 131, 198a and 199 were already known. Hence, this dissertation work presents the structural elucidation of all of these compounds using various spectroscopic (1D- and 2D NMR, optical rotation, electronic circular dichroism, infrared, ultraviolet) and high-resolution mass spectrometry methods. In addition, selected compounds (i.e., those isolated in sufficient amounts) were tested against the MTP, NF-?B inhibition, and human cancer line cytotoxicity (HeLa, HT-29, PC-3, DU-145, MDA-MB-231, and MCF-7) assays.Even though these selected compounds from H. cochinchinensis were inactive in the above-mentioned assays, this dissertation work on the isolation and characterization of the new compounds obtained led to several important observations and conclusions. For example, alkaloids 195 and 196 belong to the rare subclass of spermidine alkaloids called dovyalicins and hence, their isolation from the title plant increases the members known of this class of uncommon natural products. Furthermore, as suggested by other investigators, the isolation of compounds 202-204 with a 2,5-dihydroxybenzyl alcohol unit corroborates the proposal to re-classify the genus Homalium from the plant family Flacourtiaceae (among others) to the Salicaceae sensu lato.
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click for full text (PQDT)
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