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العنوان
Bioactive Metabolites Isolated from Different Plant Organs Of Premna Odorata Blanco /
المؤلف
Elmaidomy, Abeer Abdel Hakeem.
هيئة الاعداد
باحث / عبير عبد الحكيم الميدومى
مشرف / رباب محمد عبدالسلام
مشرف / اسماء ابراهيم اسماعيل
مشرف / حسام مختار عبدالعظيم
الموضوع
Metabolites. Metabolomics methods. Organic compounds Analysis.
تاريخ النشر
2020.
عدد الصفحات
187 P. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
العلوم الصيدلية
الناشر
تاريخ الإجازة
18/3/2020
مكان الإجازة
جامعة بني سويف - كلية الصيدلة - العقاقير
الفهرس
Only 14 pages are availabe for public view

from 210

from 210

Abstract

Premna odorata Blanco (Lamiaceae) known as “Alagaw” is a tree native to temperate and tropical Asia including the Philippines. In the Philippines, the decoction of the leaves considered a diuretic, carminative and febrifuge and used to treat endemic tuberculosis disease, vaginal irritation, coughs, beriberi, abdominal pains and dysentery. According to literature, a few phytochemical and biological investigations have conducted on premna species, P. odorata, where iridoid, flavonoids, phenyl ethanoids, and acylated rhamnopyranoses described as their major constituents present in leaves. The present study undertaken to investigate and compare P. odorata metabolites presented in its different organs (bark, wood, young stems, flowers, and fruits), using LC-HRESIMS; besides a phytochemical study targeting the bark, and young stems organs accompanied by antiproliferative, antimigratory, cytotoxic, and antioxidants activities of the isolated ones.
The Present Study includes Two Main Chapters:
Metabolomic Profiling and Cytotoxic Tetrahydrofurofuran Lignans Investigations from Premna odorata Blanco
Metabolomic profiling of different Premna odorata Blanco (Lamiaceae) organs, bark, wood, young stems, flowers, and fruits dereplicated 20, 20, 10, 20, and 20 compounds, respectively, using LC–HRESIMS. The identified metabolites belonged to different chemical classes, including iridoids, flavones, phenyl ethanoids, and lignans. A phytochemical investigation of P. odorata bark afforded one new tetrahydrofurofuran lignan, 4β-hydroxyasarinin PO1, along with fourteen known compounds. The structure of the new compound was confirmed using extensive 1D and 2D NMR, and HRESIMS analyses. A cytotoxic investigation of compounds PO1-4 against the HL-60, HT-29, and MCF-7 cancer cell lines, using the MTT assay showed that compound PO1 had cytotoxic effects against HL-60 and MCF-7 with IC50 values of 2.7 and 4.2 µg/ml, respectively. A pharmacophore map of compound PO1 showed two hydrogen bond acceptor (HBA) aligning the phenoxy oxygen atoms of benzodioxole moieties, two aromatic ring features vectored on the two phenyl rings, one hydrogen bond donor (HBD) feature, aligning the central hydroxyl group, and thirteen exclusion spheres which limit the boundaries of sterically inaccessible regions of the target’s active site.
Triple Negative Breast Cancer Suppressive Activities, Antioxidants and Pharmacophore Model of New Acylated Rhamnopyranoses from Premna odorata Blanco
Phytochemical investigation of Premna odorata Blanco, ″Lamiaceae‶ young stems afforded four new acylated rhamnopyranoses PO1‵-4‵, along with thirteen known ones. The structures of new compounds were confirmed using extensive 1D, 2D NMR, and HRESIMS analysis. The isolated compounds were tested for their cell proliferation and migration inhibition activities against the invasive human triple-negative breast cancer cells MDA-MB-231, MCF-7, and normal cell line MCF-10A as well as their radical scavenging activity using 2,2ʹ-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. Compound PO1‵ was the most active as antiproliferative, showed moderate antiproliferative effect with an IC50 value of 17.7μM. Although the proliferation inhibition was moderate both compounds PO1‵ and PO10‵ suppressed MDA-MB-231 cell migration in the wound-healing assay at 10μM concentration. Moreover, compound PO1‵ showed the highest cytotoxic activity against MCF-7 with IC50 value of 4.95 μM, with minor cytotoxic activity on MCF-10A with IC50 value of 17.35 μM using MTT assay. Meanwhile, compounds PO1‵-5‵ exhibited the highest value of DPPH radical scavenging activities with an IC50 value range of 17.5-20.43 ± 0.5 µg/ml. The pharmacophore model was generated using Molecular Operating Environment (MOE) for compounds PO1‵-5‵ showed three hydrogen bond acceptor (HBAs), one hydrogen bond donor (HBDs), one ring aromatic (Aro), and one hydrophobic (Hyd.) group. The central HBAs feature lies at a distance of 4.36 ˚A and 6.38 ˚A from the remaining two HBAs features. Also, the HBDs feature maintains a distance of 2.74 ˚A from the aromatic feature. Acylated rhamnopyranoses can be considered as good scaffolds for developing new anti-breast cancer compounds.