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Cytotoxic Activity of Diterpenoids Isolated from Salvia hypargeia

  • Bezmialem Vakif University, Faculty of Pharmacy

Abstract and Figures

Ten diterpenoids [6a-hydroxysalvinolone (1), 6a-hydroxytaxodone (2), aethiopinone (3), microstegiol (4), ferruginol (5), saprorthoquinone (6), 11,12-dioxoabieta-8,13-diene (7), taxodione (8), hypargenin A (9), hypargenin D (10)] and three triterpenoids [lupeol 3-acetate, d-oleanol 3-acetate and ß-sitosterol] were isolated from the roots of Salvia hypargeia, a plant endemic to Turkey. The crude extract and compounds 1-2, 5-10 were tested against a panel of human cancer cell lines [human breast cancer (BC 1), human lung cancer (LU 2), human colon cancer (COL 2), human epidermoidal carcinoma in mouth (KB), vinblastine-resistant KB-VI, hormone-dependent human prostate cancer (LNCaP)] as well as P388 and ASK cells in culture. The crude extract was active in all of the test systems, except KB. Isolates 1 and 8 were also found to mediate a generalized cytotoxic response.
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Ten diterpenoids [6a-hydroxysalvinolone (1), 6-
hydroxytaxodone (2), aethiopinone (3), microstegiol
(4), ferruginol (5), saprorthoquinone (6), 11,12-dioxo-
abieta-8,13-diene (7), taxodione (8), hypargenin A (9),
hypargenin D (10)] and three triterpenoids [lupeol 3-
acetate, -oleanol 3-acetate and ß-sitosterol] were iso-
lated from the roots of Salvia hypargeia, a plant
endemic to Turkey. The crude extract and compounds
1-2, 5-10 were tested against a panel of human cancer
cell lines [human breast cancer (BC 1), human lung
cancer (LU 2), human colon cancer (COL 2), human
epidermoidal carcinoma in mouth (KB), vinblastine-
resistant KB-VI, hormone-dependent human prostate
cancer (LNCaP)] as well as P388 and ASK cells in
culture. The crude extract was active in all of the test
systems, except KB. Isolates 1and 8were also found
to mediate a generalized cytotoxic response.
Salvia species (Labiatae) have been used as medicinal
plants throughout the world. They possess antifungal
and antibacterial activities (Gao et al., 1979) and are
used against tuberculosis (Dobrynin et al., 1976), as
anticancer agents and for the treatment of heart disease
(Ginda et al., 1988). In Turkish folk medicine, Salvia
species have several uses, such as antiseptic, antibacte-
rial, diuretic, hemostatic, spasmolitic, carminative and
wound healing (Baytop, 1984). Phytochemical research
revealed that the principal secondary metabolites in the
roots of Salvia species are found to be diterpenoids
which are responsible for biological activities.
In a previous study with the roots of the endemic
plant Salvia hypargeia Fisch. et Mey., collected from
eastern Turkey (Sivas), six new diterpenoids, hypar-
genins A-F (Ulubelen et al., 1988) were isolated. Later,
a NOE experiment showed that hypargenin C was tax-
odione (8) (unpublished data). Recently, we collected
the same plant from a different location, the Adana dis-
trict (southern Turkey), and studied its roots. Only three
of the previously isolated compounds were found to be
present: hypargenin A (9), hypargenin D (10) and tax-
odione (8). However, seven other diterpenes, previ-
ously obtained from other Salvia species, were isolated
from this plant for the first time. These were, 6-
hydroxysalvinolone (1) (Topcu et al., 1996), 6-
hydroxytaxodone (2) (Kupchan et al., 1968),
aethiopinone (3) (Boya et al., 1981), microstegiol (4)
(Ulubelen et al., 1992), ferruginol (5) (Cambie et al.,
1971), saprorthoquinone (6) (Lin et al., 1989), and
11,12-dioxo-abieta-8,13-diene (7) (Ulubelen et al.,
1995). In addition, -sitosterol (Swift, 1952), lupeol 3-
acetate (Ames et al., 1951) and -oleanol 3-acetate
(Djerassi & Lippman, 1955) were obtained. The diter-
penoids were either abietane (1, 2, 5, 7-10) or
rearranged abietane (3, 4, 6) types.
As reported herein, the crude plant extract and all
diterpenoids (except 3and 4) were tested against a
panel of cultured cancer cells comprised of human
breast cancer (BC 1), human lung cancer (LU1), human
colon cancer (COL 2), human epidermoidal carcinoma
in mouth (KB), vinblastine-resistant KB-VI, hormone-
dependent human prostate cancer (LNCaP), as well as
Keywords: Salvia hypargeia Fisch. et Mey., Lamiaceae, diter-
penoids, triterpenoids, cytotoxic activity.
Address correspondence to: A. Ulubelen, Faculty of Phar-
macy, University of Istanbul, 34452 Istanbul, Turkey.
Ayhan Ulubelen1, GülaçtıTopçu1, Hee-Byung Chai2and John M. Pezzuto2
1Faculty of Pharmacy, University of Istanbul, 34452 Istanbul, Turkey,Tubitak, Marmara Research Center,
Department of Chemistry, P.O. 21, TR-41470, Gebze, Kocaeli, Turkey
2Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy,
University of Illinois, Chicago, Illinois, 60612–7231, USA
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1999, Vol. 37, No. 2, pp. 148–151 © Swets & Zeitlinger
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P388 and ASK cells in culture. The crude extract was
found to be active in all the systems, except for KB.
Taxodione (8) was highly active in all systems, and the
other tested compounds showed activities in select cell
General Experimental Procedures
The spectra were recorded with the following instru-
ments. IR: Perkin-Elmer 980 in CHCl3; NMR: Bruker
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AC 200 L, 200 MHz (for 1H) and 50.32 MHz (for 13C)
in CDCl3; HRMS: ZabSpec; Optical rotation: Optical
Act. Ltd. AA-5 polarimeter; Separations: Chroma-
totron Model 7924 T; TLC: on Kieselgel 60 F254 (E.
Merck) precoated plates; CC: on silica gel 60 and
Sephadex LH-20 (Fluka).
Plant Material
The roots of Salvia hypargeia were collected from the
highland area of Adana (Tekir-Burucek) southern
Turkey, at an altitude of 1850 m. The plant was identi-
fied by Prof. Dr. Kerim Alpinar (Istanbul), and a
voucher is deposited in the herbarium of the Faculty of
Pharmacy, University of Istanbul (ISTE 68316).
Extraction and Isolation
Dried and powdered roots (1 kg) of S. hypargeia were
extracted with acetone in a Soxhlet apparatus. The fil-
tered extract was evaporated to dryness in vacuo, and
58 g of a residue were obtained. The residue was
roughly separated by column chromatography (5 70
cm) using 70–200 mesh silica gel, that was eluted with
petroleum ether, a gradient of ethyl acetate-ethanol, and
ethanol up to 100%. Fractions (1–28), (36–43),
(44–68), (69–73) and (74–87) were combined. The first
combined fraction (1–28), having only oily material,
was discarded, and the remaining combined fractions
were separated on a Chromatotron apparatus using sil-
ica gel rotors and eluting with petroleum ether and
chloroform, followed by ethanol. The compounds were
collected from the rotors under UV light (254 nm) and,
when necessary, purified on preparative TLC plates.
The amounts were: 1, 15 mg; 2, 13 mg; 3, 5 mg; 4, 8
mg; 5, 20 mg; 6, 25 mg; 7, 25 mg; 8, 18 mg; 9, 10 mg;
10, 10 mg. Optical rotations []D(recorded in CHCl3
at 22°C) are as follows: 1, 170° (c, 1.0); 2, 0° (c,
0.4); 3, 3° (c, 0.27); 4, 41.5° (c, 0.3); 5, 22° (c,
2.0); 6, 0° (c, 0.4); 7, 42.5° (c, 0.52); 8, 11° (c, 3.0);
9, 0° (c, 0.2); 10, 0° (c, 0.3).
Cytotoxic Evaluation
All compounds were evaluated for cytotoxic potential,
except 3and 4, the latter of which was reported active
against P388 (ED50 3.0 g) in a previous study
(Ulubelen et al., 1992). The evaluation procedures have
been described previously (Likhitwitayawuid et al.,
As shown in Table 1, the crude extract obtained from
Salvia hypargeia was active in all cell lines tested
except KB. The ED50 values of the diterpenoid isolates
are also given in Table 1. Taxodione (8), previously
shown to mediate antitumor activity by (Kupchan et al.,
1968) in the Walker intramuscular carcinosarcoma 256
model, was the most active substance tested. 6-
Hydroxytaxodone (2), although structurally similar to
8, did not exhibit similar activity. Compounds 2and 5
showed weak but selective activity against colon cancer
cells (Col 2) and human prostate cancer cells (LNCaP).
Compounds 1and 6mediated generalized responses.
Other compounds were either not active (7) or medi-
ated weak responses in one or two systems. The activ-
ity of 1and 8was not negated in the multidrug-resistant
KB-VI cell culture system, indicating they were not
subject to efflux by P-glycoprotein which is overex-
pressed in this cell line. None of the tested compounds
mediated a stronger cytotoxic response with KB-VI
Table 1. Cytotoxic activity of compounds 1, 2, 5-10, and ellipticinea
Compound BC1 LU1 COL2 KB KB-VI LNCaP P388
14.7 4.2 10.1 9.7 5.6 4.0 >5
2>20 >20 9.0 >20 >20 12.9 >5
5>20 >20 9.7 >20 >20 >20 >5
69.2 16.4 3.3 >20 9.1 >20 2.3
7>20 >20 >20 >20 >20 >20 >5
81.2 5.1 0.7 3.4 4.1 0.7 0.3
9>20 >20 >20 >20 >20 >20 >5
10 12.6 >20 12.3 >20 >20 >20 >5
Ellipticineb0.2 0.02 0.3 0.04 0.3 0.8 0.1
aData are given as ED50 values in g/ml, BC1, human breast cancer; COL2, human colon cancer; LU1, human lung cancer; KB, originally
derived from human nasopharyngeal cancer; KB-VI, multidrug-resistant KB; LNCaP, human prostate cancer; P388, mouse lymphocytic
bEllipticine was used as a positive control. For data obtained with additional positive control test compounds, see references (Likhitwitayawuid
et al., 1993 and Pisha et al., 1995).
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cells in the presence of vinblastine (1 g/ml), nor were
they antimitotic as judged by the ASK test system (data
not shown). The cytotoxic responses of compounds 1,
6, and 8could be due to the extensive conjugation affil-
iated with these structures. This concept should be
tested with model compounds in the future.
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Accepted: January 12, 1999
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... Ferruginol has also been found in angiosperms and has been isolated from the roots o f several species o f Salvia (Lamiaceae) (Kabouche et al., 2005;Nakanishi et al., 1983;Tan et al., 2002;Ulubelen et al., 2000Ulubelen et al., , 1999aUlubelen et al., , 1999b; Coleus barbatus (Lamiaceae) (Kelecom 1984) and also from Harpagophytum procumbens (Pedaliaceae), known as Devil's Claw (Clarkson et al., 2003a). ...
... Yang et al, (2001) used a higher bacterial titre which may account for the higher MIC. Kabouche et al. (2005) Ferruginol is known to have various biological activities:-antibacterial against Gram positive bacteria including Staphylococcus aureus (Muhammad et a l, 1992;Politi et oeL, 2003), MRSA and mycobacteria (Muhammad et al., 1992); siome antifungal activity ; activity against human colon cancer cells (Ulubelen et al., 1999a); antihypertensive activity (Ulubelen et al., 2000); ...
Antibiotic resistance by pathogenic bacteria is a major problem both in hospitals and in the community. Of particular concern is methicillin-resistant Staphylococcus aureus (MRSA), many strains of which have acquired resistance to most antibiotics. Another mode of resistance is by means of an efflux pump and many S. aureus strains have acquired pumps which confer multidrug-resistance by effluxing many different compounds out of the cell. There is an urgent need to find new antibacterials and new ways to fight these resistant strains. The rationale for this study is that since cones are essential for reproduction in conifers, the immature cones are likely to contain compounds which protect against microbial invasion. Initial screening of cones from several conifer species identified anti-staphylococcal activity, which was greatest in the hexane extracts. Bioassay guided fractionation and structure elucidation using 1-D and 2-D NMR yielded several active diterpenes from Chamaecyparis lawsoniana, Chamaecyparis nootkatensis and Pinus nigra. These compounds showed activity (2 - 64 μg/ml) against multidrug-resistant and effluxing S. aureus clinical isolates, and against epidemic MRSA strains EMRSA-15 and -16, which are the major strains found in UK hospital MRSA bacteraemias. Some of the isolated diterpenes also demonstrated activity as potentiators of antibiotic activity. Ferruginol restored oxacillin sensitivity in EMRSA-15, and moderate activity in potentiating antibiotic activity against effluxing strains was also observed for ferruginol and totarol. Efflux inhibition assays suggested that these compounds were weak efflux pump inhibitors. This study demonstrates that compounds from immature conifer cones have good antibacterial activity and some modulatory activity against resistant strains of S. aureus. These compounds are worthy of further investigation, particularly as plants produce compounds which clinically relevant bacteria are unlikely to have previously encountered.
... Twenty known secondary metabolites were isolated from the antioxidant active fractions: seven phenolic acids (rosmarinic acid (1) [25], chlorogenic acid (2) [26], caffeic acid (3) [25], 4hydroxybenzoic acid (4), benzoic acid (5) [27], salvianolic acid A (8) [28], salvianolic acid B (9) [16]), a flavone (luteolin 7-O-glucoside (6) [29]), one phthalate ester (bis-(2-ethylhexyl)benzene-1,2dicarboxylate (7) [24]), five abietane-type diterpenes (7-acetylroyleanone (10) [30], 6,7dehydroroyleanone (11) [31], ferruginol (12) [32], inuroyleanol (13) [33],12-hydroxy-6,7-secoabieta-8,11,13-triene-6,7-dial (14) [34]), four triterpenes (ursolic acid (15), [24], oleanolic acid (16) [24, taraxasterol (17) [35], lupenone (18) [36]), two steroids (β-sitosterol (19) [24], stigmasterol (20) [37]) ( Figure 1). Their structures were elucidated by spectroscopic methods (UV, IR, 1 H-and 13 C-NMR (APT), HMQC, HMBC, Mass). ...
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In the current study, the ethanol extracts prepared from the aerial parts and roots of an endemic species, Salvia cerino-pruinosa Rech. f. var. cerino-pruinosa were fractionated on silica gel columns and tested for determination of their antioxidant activity using DPPH free radical and ABTS cation radical scavenging, and cupric reducing antioxidant capacity (CUPRAC) test assays. Twenty known secondary metabolites were isolated from the active antioxidant fractions; rosmarinic acid (1), chlorogenic acid (2), caffeic acid (3), 4-hydroxybenzoic acid (4), benzoic acid (5), luteolin 7-O-glucoside (6), bis-(2-ethylhexyl)benzene-1,2-dicarboxylate (7), salvianolic acid A (8), salvianolic acid B (9), 7-acetylroyleanone (10), 6,7-dehydroroyleanone (11), ferruginol (12), inuroyleanol (13), 12-hydroxy-6,7-secoabieta-8,11,13-triene-6,7-dial (14), ursolic acid (15), oleanolic acid (16), taraxasterol (17), lupenone (18), β-sitosterol (19), and stigmasterol (20). Rosmarinic acid, which was obtained from the aerial parts, was found to be the best antioxidant compound among the isolated secondary metabolites in DPPH free radical and ABTS cation radical scavenging, and CUPRAC assays (IC50: 1.20±0.04 µg/mL, IC50: 1.74±0.06 µg/mL, A0.5: 1.22±0.02 µg/mL, respectively). Chlorogenic and caffeic acids, luteolin 7-O-glucoside, salvianolic acids A and B, and inuroyleanol exhibited also high antioxidant activity in the mentioned assays.
... Isolated compounds (1-4) have been reported for the first time from S. atropatana. However, compound 2 has also been identified in the roots of S. hypoleuca (Saeidnia et al. 2012), S. austriaca, S. tomentosa, and S. verticillata (Nagy et al. 1999), whereas, compound 3 has found in S. sclarea (Walencka et al. 2007), and compound 4 from S. prionitis (Ulubelen et al. 1999). Assessment of cytotoxic activity of isolated compounds (1-4) showed that compound 1, as a new compound, was only moderate cytotoxic against PC3 and MCF-7 cell lines with IC 50 values of 34.5 and 77.8 μg/ml, respectively, but was inactive against MDA-MB-231 cell lines (> 200 μg/ml). ...
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The purpose of this study is cytotoxicity-guided isolation of the petroleum ether fraction from the roots of Salvia atropatana for the first time, which has shown to growth inhibition and apoptosis induction in MCF-7 and PC3 cells. Bioassay-guided isolation method was conducted for finding compounds with highest cytotoxicity. Different extracts were prepared from the roots of Salvia atropatana. All extracts were tested for their cytotoxic activity against three cancer cell lines (PC3, MCF-7, and MDA-MB-231). The most cytotoxic extract was chosen for further isolation by column chromatography and HPLC. The chemical structures were determined by spectroscopic methods including 1D and 2D NMR. From the petroleum ether extract, four abietane-type diterpenoids, including a new abietane-type diterpenoid, named atropatanene (1), together with three known diterpenoids, 7α-acetoxyroyleanone (2), and a mixture of two isomers, saprorthoquinone and aethiopinone (3+4), were isolated. The latter exhibited substantial cytotoxicity with IC50 value of 8.73 μg/ml against PC3 cells and led to an increasing number of cells in the subG1 region and an increase in the amount of Bax and cleavage of PARP protein, indicating apoptotic cell death. Owing to its numerous biological activities, Salvia species could be represented as a natural potential source against several cancer cell lines.
... Ferruginol, cryptanol, lupeol, 3-acetyl-lupeol, and β-sitosterol, which were detected in the quantitative analyses of this study, were isolated from several Salvia species indicated in the literature (Ulubelen, Topcu, Chai, & Pezzuto, 1999). In this context, the fact that an easy and feasible method has been developed for the quantitative analysis of 26 secondary metabolites specific to Salvia species in GC-MS instrument found in almost every laboratory or organization makes this study important. ...
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In the present study, a GC‐MS method used for quantitative screening of 26 compounds (sclareolide, sclareol, ferruginol, cryptanol, 6,7‐dehydroroyleanone, suginal, 9,10‐dihydro‐7,8‐dimethyl‐2‐(1‐methylethyl) phenanthren‐3‐ol, sugiol, inuroyleanone, 12‐demethylmulticauline, 7α‐hydroxy‐β‐sitosterol, stigmasterol, sitosterol, salvigenin, sinensetin, α‐amyrin, lupeol, lupenone, 3‐acetyl lupeol, 1α ,21α‐dihydroxy‐2,3‐(1′1′‐dimethyl‐dioxymethylene) urs‐9(11),12‐dien, uvaol, betulin, pyxinol, lup‐(20),29‐ene‐2α‐hydroxy‐3β‐acetate, betulin 3β , 28β‐diacetate, 21α‐hydroxy,2α ,3β‐diacetoxy urs‐9(11),12‐dien) specific to Turkish Salvia species was developed and validated. According to the GC–MS analysis results, Salvia hypargeia Fisch. & C.A. Mey. roots were found to be rich in ferruginol (30787.97 µg/g extract) and lupenone (23276.21 µg/g extract), and leaves in lupeol (20625.92 µg/g extract). Additionally, the essential oil and aroma contents of this species were identified by GC‐MS technique. According to the LC‐MS/MS results, especially S. hypargeia leaf extract was rich in rosmarinic acid (38035.7 µg/g extract) and isoquercitrin (4136.91 µg/g extract). Furthermore, anticholinesterase, antiurease, antityrosinase and antielastase inhibitory, antioxidant, cytotoxic activities of the ethanol extracts, essential oil, and major components of the species were evaluated. Antioxidant potentials of all extracts of this species were quite high in all studied antioxidant methods. Moreover, butyrylcholinesterase and elastase inhibitory capacities of ferruginol, the major component of S. hypargeia roots, were notable. For these reasons, this species has a high potential for food and pharmaceutical industries. Practical applications This new GC–MS method was applied to S. hypargeia Fisch. & C.A. Mey. and it indicated that this species possessed high amount of ferruginol and lupeol, and that this species could be used for their natural sources. According to the results of the activity studies (antioxidant, anticholinesterase, tyrosinase, elastase, and cytotoxic), this method was used to exhibit which compound may be responsible for the activities. This developed and validated method could be easily applied to determine major/active/toxic secondary metabolites of Salvia species which are used and/or could be used in pharmaceutical, cosmetic, and food industries.
... In total, 13 of among the tested 41 abietane diterpenoids were determined as potential active compounds with at least 50% inhibition of AChE and/or BuChE at 200 µM concentration. These compounds, listed in the Table 2 are 12-Hydroxysapriparaquinone-3-ene (34) [49], Hypargenin E (16) [39], Ferruginol (12) [37], Bractealine (6) [34], 6-Hydroxysalvinolone (28) [45], Hormone (13) [66], Taxodione (37) [52], Royleanone (22) [44], Royleanone-12-methyl ether (25) [33], 7-Acetoxyroyleanone-12-methyl ether (27) [33], 7-Oxo-royleanone-12-methyl ether (26) [38], Inuroyleanone (23) [38], and Sugiol (36) [51]. ...
Background Alzheimer’s Disease (AD) is one of the most prevalent causes of dementia in the world, and no drugs available that can provide a complete cure. Cholinergic neurons of the cerebral cortex of AD patients are lost due to increased activity of cholinesterase enzymes. Objectives Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) are the two major classes of cholinesterases in the mammalian brain. The involvement of oxidative stress in the progression of AD is known. Thus, the objective of this study is to determine strong ChE inhibitors with anti-oxidant activity. Methods In this study, 41 abietane diterpenoids have been assayed for antioxidant and anticholinesterase (both for AChE and BuChE) properties in vitro, which were previously isolated from Salvia species, and structurally determined by spectroscopic methods, particularly intensive 1D- and 2DNMR and mass experiments. Molecular modeling studies were performed to rationalize the in vitro ChE inhibitory activity of several abietane diterpenoids compared with galantamine. Results Thirteen out of the tested 41 abietane diterpenoids exhibited at least 50% inhibition on either AChE or BuChE. The strongest inhibitory activity was obtained for Bractealine against BuChE (3.43 µM) and AChE (33.21 µM) while the most selective ligand was found to be Hypargenin E against BuChE enzyme (6.93 µM). A full correlation was not found between anticholinesterase and antioxidant activities. The results obtained from molecular modelling studies of Hypargenin E and Bractealine on AChE and BuChE were found to be in accordance with the in vitro anti-cholinesterase activity tests. Conclusion Abietane diterpenoids are promising molecules for the treatment of mild-moderate AD.
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In the present study, activity-guided isolation and structural elucidation of antioxidant secondary metabolites of ethanol extracts prepared from the root and aerial parts of Salvia rosifolia and Salvia cerino-pruinosa var. elazigensis species was aimed. The ethanol extracts of the species were fractionated and the antioxidant capacities of the fractions were determined by DPPH-free radical and ABTS-cation radical scavenging activity, and cupric-reducing antioxidant capacity (CUPRAC) assays. Isolation studies of the fractions with high antioxidant activities were carried out. Thirty nine secondary metabolites of known structure were isolated from the active extracts. 17 of the isolated compounds are in phenolic-flavonoid structure, 4 of them are in fatty acid structure, 7 of them are in abietane type diterpene structure, 2 of which are paraquinone and 5 of which are in aromatic structure, 8 of them are in triterpene structure, 2 of which are ursane, 2 of which are oleane and 4 of which are lupane structure, and 3 of them are in steroid structure. The structures of the isolated compounds were determined by UV, IR, ¹H- and ¹³C-NMR-(APT), HMQC-HMBC, LCMS-IT/TOF and GC-MS techniques. It was determined that phenolic compounds among the isolated compounds were more active than terpenoid compounds in all three methods.
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Salvia macrosiphon Boiss. is an aromatic perennial herb belonging to the family Lamiaceae. Phytochemical studies and biological activities of this plant have been rarely documented in the literature. The current study aimed to investigate antibacterial and cytotoxic activity of different fractions of aerial parts of S. macrosiphon. Also, we tried to isolate and identify cytotoxic compounds from the plant. In this respect, the hydroalcoholic extract of the corresponding parts of the plant was fractionated into four fractions. Then, antibacterial and cytotoxic activity of each fraction were examined. It was found that the chloroform fraction had a good antibacterial activity against gram-positive and gram-negative bacteria. The most potent cytotoxicity was also obtained by the n-hexane fraction comparing with etoposide as the reference drug which was selected for the study and characterization of secondary metabolites. Accordingly, 13-epi manoyl oxide (1), 6α-hydroxy-13-epimanoyl oxide (2), 5-hydroxy-7,4'-dimethoxyflavone (3), and β-sitosterol (4) were isolated and evaluated for their cytotoxic activity. Among them, compound 1 revealed significant cytotoxicity against A549, MCF-7, and MDA-MB-231. It merits mentioning that it showed high selectivity index ratio regarding the low cytotoxic effects on Human Dermal Fibroblast which can be considered as a promising anticancer candidate.
Transformed root cultures of Salvia species are rich in abietane-type diterpenoids. These compounds have various biological activities, such as antimicrobial, cytotoxic, antitumor, anti-inflammatory as well as an ability to induce apoptotic process anti- and inhibit acetyl- and butyrylcholinesterase. Some of them also possess cardioactive properties. Due to many pharmacological activities of abietane diterpenoids, scientists are actively searching for new valuable sources of biomass and its secondary metabolite. Bioactive secondary metabolites can be obtained from field plants. However, in vitro plant cultures, including transformed root cultures, may be an interesting source of these phytocompounds. Genetically modified roots (hairy roots) of Salvia species are obtained by transformation with Agrobacterium rhizogenes strains. Transformed roots have many advantages, such as the possibility of growth without exogenous phytohormones, rapid unlimited growth, genetic stability even after several years of cultivation, and often the possibility of biosynthesis of valuable secondary metabolites in higher amounts than in intact plants. Some of them are able to biosynthesize new compounds, including diterpenes, which have not been detected in the mother plant. Salvia sp. hairy roots can often be grown on a larger scale in bioreactors. After optimizing the culture conditions and/or using elicitors, they are able to biosynthesize abietane diterpenoids in quantities significantly exceeding not only mother plants but also those grown in flasks. The above properties of this kind of plant cultures make them an interesting experimental model in studies aimed at increasing the productivity of biologically active diterpenes.
A new type of bisnorditerpene, salviolone (4) having a benzotropolone moiety has been isolated together with two other nor- and bisnorditerpenes 1 and 2 from the fresh root of . The compounds exhibit cytotoxic activity against Vero cells.
From the roots of Salvia prionitis a new diterpenoid, salvonitin was isolated and its structure elucidated on the basis of its 1H and 13C NMR spectra.
Microstegiol, a diterpene with a new carbon skeleton, was isolated from Salvia microstegia. Determination of the carbon framework and substitution pattern of the isolate was made by series of selective INEPT, COSY and NOE experiments, which also permitted the unambiguous assignment of the 13C NMR spectrum.
A new orthonaphthoquinone diterpene has been isolated from Salvia aethiopis and given the trivial name aethiopinone. The structure of this natural
From the acetone extract of the roots of Salvia napifolia, eight known diterpenoids—horminone, 7-acetylhorminone, ferruginol, pachystazone, cryptanol, cryptojaponol, sugiol and microstegiol—and five new diterpenes—6,12,14-trihydroxyabieta-6,8,11,12-tetraen, 7,20-epoxyroyleanone, 1-oxoferruginol, 6-oxoferruginol and 11,12-dioxoabieta-8,13-dien—were obtained. The structures of the new and the known compounds were established by spectral methods.
From the roots of Salvia prionitis Hance two new diterpenoids, salvinolone and salvinolactone, and two 4,5-seco-5,10-friedo-abietane diterpenoids, 4-hydroxy sapriparquinone and saprorthoquinone, have been isolated and their structures elucidated on the basis of their 1H and 13C NMR spectra.