Growth inhibitory activity of biflavonoids and diterpenoids from the leaves of the Libyan Juniperus phoenicea against human cancer cells

Abstract

Three biflavonoids [cupressuflavone (1), amentoflavone (2), and sumaflavone (3)], four diterpenoids [13-epi-cupressic acid (4), imbricatholic acid (5), 3-hydroxysandaracopimaric acid (6), and dehydroabietic acid (7)], and one lignan [β-peltatin methyl ether (8)] were isolated from the cytotoxic fractions of the extracts of the leaves of the Libyan Juniperus phoenicea L. The structures of these compounds were elucidated by spectroscopic means. Cytotoxicity of compounds 1-6 were assessed against the human lung cancer cell line A549 using the MTT assay. Compounds 1 and 3 showed cytotoxicity against the A549 cells (IC 50 = 65 and 77 μM, respectively), whereas compound 2 did not show any activity. Diterpenes 4-6 exhibited weak cytotoxicity against the A549 cells with the IC 50 values of 159, 263, and 223 μM, respectively. The cytotoxicity of each compound was compared with the anticancer drug, etoposide (IC 50 = 61 μM). Cupressuflavone (1) was evaluated also for cytotoxicity against both the human PC3 cancer cell line and the normal prostate cell line (PNT2), and this compound revealed a high degree of cytotoxic selectivity towards the prostate cancer cells (PC3), with IC 50 value of 19.9 μM, without any evidence of cytotoxicity towards the normal prostate cell line (PNT2).

Anti-Lymphangiogenic Terpenoids from the Heartwood of Taiwan Juniper, Juniperus chinensis var. tsukusiensis

“…Thus, the structure of compound 5 was elucidated as 1β,2β-epoxy-9α-hydroxy-8( 14),11-totaradiene-3,13-dione. By comparing the spectroscopic data ([a]D, UV, IR, NMR, and MS) of known compounds with the literature data, the known diterpenes were identified to be totarolone (6) [41], 3β-hydroxytotarol (7) [42], 7-oxototarol (8) [41], and 1-oxo-3β-hydroxytotarol ( 9) [41], 5,6-dehydrosugiol methyl ether (10) [43], sandaracopimaric acid (11) [35], 3,18dihydroxypimara-8( 14),15-diene ( 12) [44], secoabietane dialdehyde (13) [43], communic By comparing the spectroscopic data ([a] D , UV, IR, NMR, and MS) of known compounds with the literature data, the known diterpenes were identified to be totarolone (6) [41], 3β-hydroxytotarol (7) [42], 7-oxototarol (8) [41], and 1-oxo-3β-hydroxytotarol (9) [41], 5,6-dehydrosugiol methyl ether (10) [43], sandaracopimaric acid (11) [35], 3,18dihydroxypimara-8( 14),15-diene (12) [44], secoabietane dialdehyde (13) [43], communic acid (14) [43], and (12R, 13S)-dihtdroxylabda-8(17),14-dien-19-oic acid (15) [45]. Additionally, the known sesquiterpenes were identified to be 2-himachalen-6-ol ( 16) [36], 3-himachalen-6-ol (17) [36], chinensiol (18) [36], ar-himachalene (19) [36], 12-hydroxyα-longipinene (20) [35], 15-hydroxyacora-4(…”

“…Furthermore, the high resin content makes Juniperus wood more resistant to decay and infestation, making it a valuable material in woodworking projects. Some characteristic phytochemicals have been isolated from Juniperus, including acetophenones, monoterpenes, sesquiterpenes, diterpenes, flavonoids, lignans, and phenylpropanoides, mainly terpenoids [5][6][7][8][9][10][11][12][13][14][15][16][17]. The representative terpenoids in Juniperus include α-pinene, camphene, β-pinene, sabinene, myrcene, limonene, imbricatolic acid, junicedral, trans-communic acid, and isocupressic acid [18,19].…”

Hinokiflavone and Related C–O–C-Type Biflavonoids as Anti-cancer Compounds: Properties and Mechanism of Action

“…The structure of MMP-9 is presented (PDB code: 1GKC), with a detailed view of the hinge region which delimits the catalytic active site. Molecular modeling has predicted that HNK can bind deeply into the active site cavity, engaging multiple interactions with the protein, notably through 3 hydrogen bonds with the NH groups of Gly-215, Tyr-423 and C = O group of Glu-402 (arrows), plus hydrophobic contacts with several amino acids (italicized, dashed lines), as represented (adapted from [75]) isoginkgetin [99], japoflavone D [112], sumaflavone [113] and cupressuflavone [113,114], but these C-C-type biflavonoids will not be further discussed here.…”

In vitro induction of mitotic catastrophe as a therapeutic approach for oral cancer using the ethanolic extract of Juniperus squamata

“…Among these species, Juniperus communis has shown a notable ability to induce cell cycle arrest or apoptotic cell death in various types of cancer cell lines through regulation of Bcl-2 family proteins, p53 signaling, or the Akt pathway (14,15). Similarly, the cytotoxic properties of bioactive compounds derived from Juniperus phoenicea have been evaluated in several cancer cell lines (16). However, unlike other Juniperus species, the biological activity of Juniperus squamata (J. squamata; also referred to as Sabina squamata) against cancer has not yet been fully studied.…”