Nuntavan BunyapraphatsaraSudarat Homhual2023-08-252023-08-25200620062023Thesis (Ph.D. (Pharmaceutical Chemistry and Phytochemistry))--Mahidol University, 20069740471161https://repository.li.mahidol.ac.th/handle/20.500.14594/88757Studies on cancer chemopreventive activities were carried ou t on the flowers of Bruguiera gymnorrhiza (L.) Savigny. The powdered flowers were successively extract ed with petroleum ether, chloroform, ethyl acetate and methanol. These extracts were tested for cancer chemopreventive activity including inhibition of cyclooxygenase (COX) both in COX-1 and COX-2, luciferase activity by activation of antioxidant-re ponse element (ARE) and inhibition of nuclear factor kappa B (NF κ B). Crude chloroform extract was shown to inhibit COX-1 with IC 50 value of 2.98 μ g/ml. All extracts were found to be inactive in COX-2 inhibition. Petroleum ether and ethyl acetate extracts exhibited activat ion of ARE with EC 50 values of 0.71 and 12.9 μ g/ml, respectively. Chloroform and methanol extracts were inactive. Three extracts of petroleum ether, chloroform and ethyl acetate demonstr ated inhibition of NF κ B with IC 50 values of 19.7, 0.03 and 1.85 μ g/ml, respectively. Because of their biological activities, chloroform and petroleum ether extracts were submitted f or further separation. The petroleum ether extract was separated using column chromatography to afford six compounds of K1, K2, K8, K10, K11 and K12. The structures of compounds K2, K1 and K8 were determined on the basis of physical and spectroscopic data to be novel dammarane triterpenoids; 1 β ,20( S )-dihydroxydammar-24(25)-ene-3 β - O -stearate, 11 α ,20( S )- dihydroxydammar-24(25)-ene-3 β - O -stearate and 1 β ,20( S )-dihydroxy-25-hydroperoxydammar -23(24)-ene-3 β - O -stearate, and given the trivial names, bruguierin A, bruguierin B and bruguierin C, respectively. Compounds K10, K11 and K12 have been identified as taraxerone, nonacosane and heptacosane, respectively. The investigation of chloroform extract has led to six compounds: K3, K7, K9, K4, K5 and K6. The structure elucidation indicated that compounds K3, K7 and K9 were cyclic 4-hydroxy-dithiosulfonate. Compound K3 was assigned to be 1,1-dioxo-1 λ 6 -[1,2]dithiolan-4-ol, a novel cyclic dithiosulfonate and given the trivial name, bruguiesulfurol. Compounds K7, K9, K5, K4 and K6 were identifi ed by comparing them with previous reports as brugierol, isobrugierol, triac ontanol, daucosterol and daucosterol 6 ' - O -palmitate, respectively. Compounds K2 and K7 demonstrated inhibition of COX-2 with IC 50 values of 6.6 and 6.1 μ M, respectively. Compounds K2, K7 and K9 were found to inhibit NF κ B with IC 50 values of 7.8, 85.0 and 14.5 μ M, respectively. Compounds K1, K2, K3, K7, K8 and K9 exhibited activation of ARE with EC 50 values of 13.3, 9.5, 56.7, 3.5, 17.9 and 1.8 μM, respectively. Compounds K7, K9 and K10 also showed the inhibition of TP A-induced ornithine decarboxylase (ODC) activity and induction of quinone reduc tase (QR) activity. Compounds K9 and K10 inhibited ODC, with an IC 50 values of 43.5, 47.2 μM, respectively whereas K10 exhibited induction of QR with induction ratio (IR) 1.1xxii, 191 leaves : ill. (some col.)application/pdfengBruguiera gymnorrhizaAntineoplastic Agents PhytogenicLuciferasesProstaglandin-Endoperoxide SynthaseMahidol University