Cytotoxic and antibacterial activities of the analogues of pogostone

Article abstract of DOI:10.1016/j.fitote.2015.08.003

Six new (A5-A6, A8-A11) and six known (A1-A4, A7, PO) α-pyrone compounds were synthesized with dehydroacetate and aldehydes in tetrahydrofuran at room temperature. And their structures were determined by ¹H-NMR, ¹³C-NMR and mass spec

Full text of DOI:10.1016/j.fitote.2015.08.003

Fitoterapia 106 (2015) 41–45
Contents lists available at ScienceDirect
Fitoterapia
journal homepage: www.elsevier.com/locate/fitote
Cytotoxic and antibacterial activities of the analogues of pogostone
d
a
Zheng-wei Tang a,b,c, Cheng Peng a,b,c, , Min Dai , Bo Han
⁎
a
College of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Chengdu University of Traditional Chinese Medicine, State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu 611137,
b
China
c
The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Chengdu 611137, China
Department of Pharmacology, Chengdu Medicine College, Chengdu 610065, China
d
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 June 2015
Received in revised form 5 August 2015
Accepted 6 August 2015
Available online 10 August 2015
Six new (A5-A6, A8-A11) and six known (A1-A4, A7, PO) α-pyrone compounds were synthesized with
dehydroacetate and aldehydes in tetrahydrofuran at room temperature. And their structures were determined
by 1H-NMR, 13C-NMR and mass spectroscopy. In the bioscreening experiments, ten compounds (A1-A5, PO,
A7-A10) exhibited antibacterial activities against Staphylococcus aureus ATCC 25923 with minimum inhibitory
concentration (MIC) values of 4–512 mg/L, and nine compounds (A1-A5, PO, A7–A8, A10) exhibited antibacterial
activities against Methicillin-resistant S. aureus (MRSA) ATCC 43300 with MIC values of 4–256 mg/L. Moreover,
compound A10 showed the highest antibacterial activity against S. aureus ATCC 25923 and MRSA with MIC values
of 4 mg/L, while the MIC values of Amoxicillin were 8 mg/L and N256 mg/L, respectively. Two compounds (A8
and PO) exhibited antibacterial activities against Escherichia coli ATCC 25922 with MIC values of 32–512 mg/L.
However, only one compound (A8) exhibited significant antibacterial activity against Pseudomonas aeruginosa
CVCC 3360 with MIC value of 256 mg/L. Moreover, A10 exhibited significant inhibition of proliferation in the
four cell lines MCF-10, A549, A2780 and MFC, and showed stronger inhibitive activity of these four selected
cell lines than cisplatin in the cytotoxic assay. Thus, this study suggests that pogostone analogues, especially
A10, represented a kind of promising antibacterial and antineoplastic agents.
Keywords:
Pogostone
Analogues
Synthesis
Antibacterial and cytotoxic activities
MRSA
© 2015 Elsevier B.V. All rights reserved.
1. Introduction
Pogostone (PO) is the effective component of the antimicrobial and
insecticide activities of Pogostemonis Herba [6,7], which has a variety
Since the antibiotics were introduced into clinical practice bacte-
rial pathogens have been developing resistance, which reduces or
eliminates the effectiveness of these agents [1,2]. In addition,
opportunistic pathogens with innate resistance to antibiotics have
become emerging problems, particularly in hospital settings. In de-
veloped countries, such as USA, bacterial strains that have acquired
multiple drug resistance, include Enterococcus faecium, Staphylococ-
cus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudo-
monas aeruginosa and Enterobacter species, and S. aureus is the
most serious one [3]. For example, methicillin-resistant S. aureus
(MRSA) was discovered in a healthcare setting and once thought to
be a small problem, but now MRSA infections are becoming very
common at anywhere. Meanwhile, MRSA have become resistant to
the multiple classes of antibiotics (beta lactams, macrolides, quino-
lones, etc.), including glycopeptides vancomycin, the common drug
of last resort [4,5].
of activities, including anti-inflammatory, analgesic, antipyretic, anti-
emetic, antimicrobial actions, anti-mutation, immunological regulation,
anti-gastric ulcer, insecticide and inhibitory activity on platelet-
activating factor (PAF) activation [8–16]. In the previous studies re-
vealed that pogostone had a notable activities against Candida albicans
and insect [17,18], oral and topical PO administration effectively re-
duced the bacterial load in vagina of vulvovaginal S. aureus mice models
[19], and protected mouse from the challenge experiment with lethal
dose of S. aureus, Escherichia coli and MRSA [20,21]. Moreover, the
pharmacolinetics assay showed that PO was easily absorbed after oral
administration in rat [22,23]. The previous studies manifested that the
PO and its analogues may have considerable prospects in the antibacte-
rial application.
As part of our ongoing search of promising new antibacterial com-
pounds, we synthesized pogostone and its analogues. Six new (A5–A6,
A8–A11) and six known (A1–A4, A7, PO) α-pyrone compounds were
synthesized and their chemical structures were given in Fig. 1. Their po-
tential antimicrobial effects on S. aureus ATCC 25923, E. coli ATCC 25922,
P. aeruginosa CVCC 3360 and MRSA ATCC 43300 were evaluated. Addi-
tionally, their cytotoxic activities against mammalian tumor cell lines
MCF-10, A549, A2780 and MFC were also evaluated.
⁎
Corresponding author at: College of Pharmacology, Chengdu University of Traditional
Chinese Medicine, Chengdu 611137, China.
http://dx.doi.org/10.1016/j.fitote.2015.08.003
0367-326X/© 2015 Elsevier B.V. All rights reserved.

42
Z. Tang et al. / Fitoterapia 106 (2015) 41–45
Fig. 1. Synthesis of pogostone and its analogues.
2. Materials and methods
well) to achieve the wanted concentrations. Each compound was deter-
mined in triplicate for each inhibitor concentration. The microplates
were incubated at 37 °C for 24 h, with shaking at 200 × g. After incuba-
tion, the plates were tested with the Multimode Reader (Thermo Scien-
tific Skanlt Software for Varioskan Flash version 2.4.5, USA) at 600 nm.
The highest dilution with no bacterial growth was detected and recog-
nized as the MIC. Then, 5 μL solutions with no bacterial growth were
added to Mueller-Hinton Agar (MHA) (OXOID LTD., BAINGSTOKE,
HAMPSHIRE, ENGLAND) plates and incubated at 37 °C for 24 h for
MBC test. The highest dilution with no bacterial growth on MHA plates
was identified as the MBC. Blank 5% DMSO without any compounds was
diluted at the same time to the highest concentration of the compounds
as the blank controls.
2.1. Chemical synthesis
The synthesis route used to synthesize the pogostone and its ana-
logues is outlined in Fig. 1. Under a nitrogen atmosphere, dehydroacetate
(DHA), aldehydes and stirrer were added into the dry tetrahydrofuran
(THF), which just rightly could dissolve the solid at a temperature
of 5 °C. Briefly, a secondary amine catalyst (NOH) was added into
the mixture and stirring for 2 ~ 6 h at the room temperature. Upon
completion, the reaction mixture was plated into refrigerator at
−4 °C for 30 min, then filtrated and the residue was washed with lit-
tle ethyl acetate then purified by normal hexane to obtain yellow
crystals (A1–A11).
The yellow crystals were dissolved in ethyl acetate, and transferred
in a hydrogenator with 5% Pd–C. The hydrogen was introduced in the
hydrogenator and the pressure was maintained at 0.1 Mp for 4 h with
constant stirring at room temperature. Upon completion, the reaction
mixture was diluted with acetone, filtered through a double-deck quan-
titative filter paper, followed by washing the paper with the acetone.
The liquid was concentrated under reduced pressure and then separat-
ed by G254 Silicagel column with moving phase (petroleum ether: ethyl
acetate = 10:1). The products were concentrated under reduced
pressure and purified by n-hexane. There were no significant differ-
ences in the cytotoxic and antibacterial activities of these compounds
comparing to pogostone, thus the data and compounds did not show.
The resulting compounds PO and A1–A11 were characterized by
1H-NMR, 13C-NMR and mass spectroscopy.
2.5. Cell proliferation assay
Cytotoxic activity was evaluated using the CellTiter 96 Aqueous Non-
Radioactive Cell Proliferation Assay (MTT) following the manufacturer's in-
structions using the human breast (MCF-10), lung (A549), ovarian (A2780)
and mice gastric (MFC) carcinoma cell lines [25]. All types of cells were
grown in DMEM with 5% fetal calf serum, and harvested using Tryspin/
EDTA and diluted to 1.0 × 105 cells per well in a 96-well plate. Ten concentra-
tions covering five orders of magnitude were tested with three replicates per
concentration. Cells were incubated for 48 h at 37 °C with 5% CO2. MTT/PBS
solution was added to the wells and absorbance was measured at 490 nm
four hours later. Data was analyzed using Graphpad Prism version 5.0
(GraphPad Software, La Jolla, CA) using a variable slope inhibition dose re-
sponse curve. And the cisplatin was the positive control with the same
conduction.
2.2. Bacteria
3. Results and discussion
S. aureus ATCC 25923 (American Type Culture Collection), E. coli
ATCC 25922, P. aeruginosa CVCC 3360 (China Veterinary Culture Collec-
tion Center), and Methicillin-resistant S. aureus ATCC 43300. Bacteria
were cultured in the Trypticase Soy broth (TSB) at 37 °C.
3.1. The spectral data of compounds
To the best of our knowledge, although the study on the synthesis of
pogostone had been reported [17], this route could raise the yield of
pogostone from 4.48% to 58% and reduce the reaction time. Moreover,
the reaction could be accomplished at the room temperature. The
structures of pogostone and its analogues were shown in Fig. 2. The
spectral data of each compound is given below:
2.3. Carcinoma cell lines
Human breast carcinoma cells MCF-10, human lung carcinoma cells
A549, human ovarian carcinoma cells A2780 and mice gastric carcino-
ma cells MFC. All types of cells were grown in DMEM with 5% fetal calf
serum (Hohhot Cao Yuan Lv Ye Bio-engineering Materials Co., Ltd.
140101, Shanghai, China) at 37 °C with 5% CO2.
4-hydroxy-6-methyl-3-(4-methylpentanoyl)-2H-pyran-2-one
(PO): white crystal, yield 58%; 1HNMR (CDCl3, 400 MHz): δ 6.04
(s, 1H), 3.21 (t, J = 7.8 Hz, 2H), 2.51 (s, 3H), 1.61 (m, 1H), 1.48
(m, 2H), 0.89 (d, J = 6.4 Hz, 6H); 13CNMR (CDCl3, 100 MHz): δ
207.64, 181.02, 168.72, 158.97, 100.23, 99.41, 38.64, 31.98,
27.02, 21.56, 21.54, 20.60; ESI HRMS: calcd. For C12H16O4 + Na
224.1049, found 224.1051;
2.4. Determination of minimal inhibitory concentrations and minimal
bactericidal concentrations
The minimum inhibitory concentration (MIC) of each compound
was determined using a broth microdilution assay [24]. The compounds
and positive control (Amoxicillin) were diluted in 5% DMSO and added
to TSB medium (0.1 mL) with bacterial inoculums (1.0 × 104 CFU per
(E)-4-hydroxy-6-methyl-3-(4-methylpent-2-enoyl)-2H-pyran-
2-one (A1): yellow crystal, yield 82%; 1H-NMR (400 MHz, CDCl3)

Z. Tang et al. / Fitoterapia 106 (2015) 41–45
43
Fig. 2. Structure of pogostone and its analogues.
δ 6.86 (dd, J1 = 11.2 Hz, J2 = 6.8 Hz, 1H), 6.27 (d, J = 11.2 Hz, 1H),
6.08 (s, 1H), 2.36 − 2.24 (m, 1H), 2.07 (s, 3H), 1.91 (d, J = 7.2 Hz,
3H), 1.78 (d, J = 7.2 Hz, 3H) ppm; 13C-NMR (100 MHz, CDCl3) δ
181.23, 174.83, 163.93, 162.44, 152.44, 126.60, 103.41, 100.66, 36.01,
18.29, 17.55, 16.48 ppm; ESI HRMS: calcd. For C12H14O4 + Na
245.0790, found 245.0793;
(E)-4-hydroxy-6-methyl-3-(pent-2-enoyl)-2H-pyran-2-one (A2):
yellow crystal, yield 88%. 1H-NMR (400 MHz, CDCl3) δ 6.81 − 6.79
(m, 1H), 6.37 (d, J = 11.2 Hz, 1H), 6.02 (s, 1H), 2.19 (s, 3H), 2.02 −
1.86 (m, 2H), 1.14 (t, 3H) ppm; 13C-NMR (100 MHz, CDCl3) δ
181.16, 175.03, 164.95, 162.80, 152.38, 134.88, 105.87, 103.13, 27.89,
21.48, 17.59 ppm; ESI HRMS: calcd. For C11H12O4 + Na 231.0633,
found 231.0629;
4-hydroxy-6-methyl-3-((2E, 4E, 6E)-octa-2, 4, 6-trienoyl)-2H-
pyran-2-one (A5): yellow crystal, yield 82%. 1H-NMR (400 MHz,
CDCl3) δ 7.25 (dd, J1 = 12.4 Hz, J2 = 9.6 Hz, 1H), 6.77 (d, J =
12.4 Hz, 1H), 6.32-6.25 (m, 2H), 6.12 (dd, J1 = 12.8 Hz, J2
=
9.2 Hz, 1H), 5.94 (d, J = 0.8 Hz, 1H), 5.83 − 5.76 (m, 1H), 2.25 (s,
3H), 1.88 (d, J = 7.2 Hz, 3H) ppm; 13C-NMR (100 MHz, CDCl3) δ
181.27, 175.24, 165.74, 162.42, 137.58, 133.53, 133.44, 128.70,
128.52, 121.37, 95.28, 93.59, 35.26, 22.30 ppm; ESI HRMS: calcd.
For C14H14O4 + Na 269.0790, found 269.0792;
3-((2E, 4E)-5-(furan-2-yl)penta-2,4-dienoyl)-4-hydroxy-6-methyl-
2H-pyran-2-one (A6): yellow crystal, yield 85%. 1H-NMR (400 MHz,
CDCl3) δ 7.87 (d, J = 8.0 Hz, 1H), 7.55 (dd, J1 = 12.4 Hz, J2 = 9.6 Hz,
1H), 7.16 (d, J = 8.0 Hz, 1H), 7.02 − 6.88 (m, 3H), 6.48 (dd, J1
=
(E)-3-(hex-2-enoyl)-4-hydroxy-6-methyl-2H-pyran-2-one (A3):
yellow crystal, yield 87%. 1H-NMR (400 MHz, CDCl3) δ 6.79 − 6.72
(m, 1H), 6.45 (d, J = 11.2 Hz, 1H), 6.12 (s, 1H), 2.30 − 2.24 (m,
5H), 1.66 − 1.53 (m, 2H), 0.86 (t, J = 7.2 Hz, 3H) ppm; 13C-NMR
(100 MHz, CDCl3) δ 184.48, 174.58, 164.08, 162.68, 150.08, 129.44,
106.35, 101.77, 36.43, 25.73, 24.72, 16.52 ppm; ESI HRMS: calcd.
For C12H14O4 + Na 245.0790, found 245.0795;
3-((2E, 4E)-hexa-2,4-dienoyl)-4-hydroxy-6-methyl-2H-pyran-2-
one (A4): yellow crystal, yield 81%. 1H-NMR (400 MHz, CDCl3) δ
7.81 (d, J = 11.2 Hz, 1H), 7.30 (d, J = 11.2 Hz, 1H), 6.62 (d, J =
11.2 Hz, 1H), 6.13 (s, 1H), 5.80 − 5.76 (m, 1H), 2.12 (s, 3H), 1.80
(d, J = 7.2 Hz, 3H) ppm; 13C-NMR (100 MHz, CDCl3) δ 180.69,
173.68, 162.25, 160.10, 142.24, 134.00, 129.94, 123.37, 101.82,
100.32, 23.16, 19.63 ppm; ESI HRMS: calcd. For C12H12O4 + Na
243.0633, found 243.0625;
10.0 Hz, J2 = 6.0 Hz, 1H), 6.13 (s, 1H), 2.21 (s, 3H) ppm; 13C-NMR
(100 MHz, CDCl3) δ 175.47, 172.85, 164.76, 163.68, 149.30, 148.99,
137.40, 132.71, 124.57, 120.68, 116.03, 115.16, 102.75, 100.25,
23.77 ppm; ESI HRMS: calcd. For C15H12O5 + Na 295.0582, found
295.0590;
4-hydroxy-6-methyl-3-((2E,4E)-5-phenylpenta-2,4-dienoyl)-2H-
pyran-2-one (A7): yellow crystal, yield 78%. 1H-NMR (400 MHz,
CDCl3) δ 7.51 − 7.22 (m, 6H), 6.78 (d, J = 11.2 Hz, 1H), 6.28 (dd,
J1 = 12.4 Hz, J2 = 9.6 Hz, 1H), 6.18 (d, J = 12.4 Hz, 1H), 6.01 (s,
1H), 2.09 (s, 3H) ppm; 13C-NMR (100 MHz, CDCl3) δ 181.42,
175.54, 164.32, 163.64, 150.23, 140.13, 132.84, 129.40, 129.17,
128.97, 128.93, 128.01, 125.27, 120.85, 100.39, 95.82, 20.44 ppm;
ESI HRMS: calcd. For C17H14O4 + Na 305.0790, found 305.0794;
3-((2E,4Z)-4-bromo-5-phenylpenta-2,4-dienoyl)-4-hydroxy-6-
methyl-2H-pyran-2-one (A8): yellow crystal, yield 88%. 1H-NMR

44
Z. Tang et al. / Fitoterapia 106 (2015) 41–45
Table 2
(400 MHz, CDCl3) δ 7.59 (d, J = 9.6 Hz, 1H), 7.26 − 7.11 (m, 5H),
Minimal bactericidal concentrations (MBCs) against bacteria of compounds (mg/L).
6.87 (s, 1H), 6.59 (d, J = 9.6 Hz, 1H), 6.07 (s, 1H), 2.29 (s, 3H)
ppm; 13C-NMR (100 MHz, CDCl3) δ 181.41, 174.52, 162.25,
160.10, 144.95, 134.04, 133.14, 130.51, 128.49, 126.34, 126.31,
125.28, 123.37, 115.03, 102.46, 100.86, 19.84 ppm; ESI HRMS:
calcd. For C17H13BrO4 + Na 382.9895, found 382.9891;
4-hydroxy-6-methyl-3-((2E,4E)-4-methyl-5-phenylpenta-2,4-
dienoyl)-2H-pyran-2-one (A9): yellow crystal, yield 85%. 1H-
NMR (400 MHz, CDCl3) δ 7.49 (d, J = 12.4 Hz, 1H), 7.28 − 7.13
(m, 5H), 6.59 (d, J = 12.4 Hz, 1H), 6.25 (s, 1H), 6.06 (s, 1H), 2.26
(s, 3H), 2.19 (s, 3H) ppm; 13C-NMR (100 MHz, CDCl3) δ 181.32,
175.47, 165.21, 164.48, 155.61, 149.22, 132.71, 131.32, 128.85,
127.86, 127.06, 126.39, 124.57, 122.10, 99.01, 96.84, 23.77,
23.57 ppm; ESI HRMS: calcd. For C18H16O4 + Na 319.0946, found
319.0951;
compound
MBC(mg/L)
S. aureus
E. coli
P. aeruginosa
MRSA
ATCC 25923
ATCC 25922
CVCC 3360
ATCC 43300
Amoxicillin
Pogostone
A1
A2
A3
A4
A5
A6
A7
8
256
128
128
256
64
128
512
N256
N1024
N1024
N1024
N1024
N1024
N1024
N1024
N1024
256
N256
512
128
256
256
128
16
N1024
256
N1024
N1024
N1024
N1024
N1024
N1024
N1024
32
8
N1024
256
64
A8
64
A9
A10
A11
N1024
4
N1024
N1024
N1024
N1024
N1024
N1024
N1024
N1024
8
N1024
3-((2E,4E)-5-(4-chlorophenyl)penta-2,4-dienoyl)-4-hydroxy-6-
methyl-2H-pyran-2-one (A10): yellow crystal, yield 86%. 1H-NMR
(400 MHz, CDCl3) δ 7.40 (d, J = 8.0 Hz, 2H), 6.99 − 6.81 (m, 3H),
6.71 (d, J = 11.2 Hz, 1H), 6.51 − 6.38 (m, 2H), 5.98 (s, 1H), 2.26
(s, 3H) ppm; 13C-NMR (100 MHz, CDCl3) δ 180.99, 173.71, 160.57,
159.03, 148.99, 137.40, 135.26, 134.71, 131.32, 128.06, 124.57,
124.07, 122.09, 119.97, 102.38, 93.64, 23.77 ppm; ESI HRMS: calcd.
For C17H13ClO4 + Na 339.0400, found 339.0397; and
4-hydroxy-3-((2E,4E)-5-(4-methoxyphenyl)penta-2,4-dienoyl)-6-
methyl-2H-pyran-2-one (A11): yellow crystal, yield 82%. 1H-NMR
(400 MHz, CDCl3) δ 7.81 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 11.2 Hz,
1H), 7.28 − 7.20 (m, 3H), 6.89 − 6.77 (m, 2H), 6.17 (s, 1H), 3.60
(s, 3H), 1.89 (s, 3H) ppm; 13C-NMR (100 MHz, CDCl3) δ 179.38,
173.71, 164.38, 162.05, 157.40, 151.82, 141.90, 129.91, 129.10,
127.65, 125.97, 123.58, 113.25, 112.90, 95.42, 93.64, 52.37,
17.74 ppm; ESI HRMS: calcd. For C18H16ClO5 + Na 335.0895, found
335.0890.
against all the tested strains. The MBC results in Table 2 showed that
the best compounds (A5 and A10) also had significant antibacterial
activity against S. aureus comparing to PO, with 8 mg/L of A5 and
4 mg/L of A10. As per CLSI standards, a MBC/MIC ratio of 1 to 2 is consid-
ered indicative of bactericidal behavior [26]. By contrast, almost of com-
pounds exhibit identical MBC and MIC values (i.e., MBC/MIC ratios of 1
to 2) for S. aureus, indicative of a bactericidal mode of action against
S. aureus as well as MRSA. Both Tables 1 and 2 indicated that the synthe-
sis compounds showed a strong difference between S. aureus (Gram
positive bacteria) and E. coli, P. aeruginosa (Gram negative bacteria).
MIC was determined as the lowest concentration that cause com-
plete growth inhibition (bacteriostatic), while the MBC was the lowest
concentration that killed 99.9% of the cells (bactericidal). These two
kind of antibacterial effects do not exactly share the same mechanism.
The mechanism of antibacterial effect can be summarized as the action
on the cell (directly or indirectly) wall and plasma membrane, and the
synthesis inhibition on bacterial DNA and RNA. Our results showed
the antibacterial effects on Gram positive bacteria and Gram negative
bacteria were very difference, and there was a huge difference in the
composition of Gram positive and negative bacteria. Therefore, we
guessed the action on the cell wall may be the mechanism of these com-
pounds and could be confirmed in the further study.
3.2. In vitro antibacterial activity of the compounds
We synthesized pogostone and a series of its analogues and evaluat-
ed their antibacterial activities. Table 1 summarized the MIC results of
the antibacterial assays against bacteria. In contrast to the results that
all compounds had no antibacterial activities against P. aeruginosa,
except A8 (256 mg/L); A5 (8 mg/L) and A10 (4 mg/ L) showed
a strong activity against S. Aureus including MRSA, 32 and 64
times that of pogostone (256 mg/L), respectively. But A6 and A11
(MIC N 1024 mg/L) showed no appreciable antibacterial activities
3.3. In vitro antiproliferative activity of the compounds
Meanwhile, their cytotoxic activities against the mammalian tumor
cell lines were evaluated. This is the first report on the antiproliferative
activity evaluation of pogostone and its analogues. The cytotoxic activi-
ties of the compounds against human breast (MCF-10), lung (A549),
ovarian (A2780) and mice gastric (MFC) carcinoma cell lines were
Table 1
Minimal inhibitory concentrations (MICs) against bacteria of compounds (mg/L).
Table 3
Cytotoxic activities (IC50) of the compounds.
Compound
MIC(mg/L)
S. aureus
E. coli
P. aeruginosa
MRSA
compound
IC50(mg/L)
MCF-10
ATCC 25923
ATCC 25922
CVCC 3360
ATCC 43300
A549
A2780
21.04
62.16
212.04
N256
N256
168.24
44.26
221.04
82.64
MFC
18.06
58.21
N256
216.24
184.26
88.26
62.10
N256
112.04
26.15
210.32
5.41
Amoxicillin
Pogostone
A1
A2
A3
A4
A5
A6
A7
A8
A9
A10
A11
0.5
256
64
128
128
64
16
512
N256
N256
256
64
256
128
128
8
N1024
128
64
1024
4
Cisplatin
Pogostone
A1
A2
A3
A4
A5
A6
A7
A8
A9
A10
A11
10.21
54.65
112.42
142.15
110.26
68.21
36.52
150.23
88.12
14.12
48.24
N1024
N1024
N1024
N1024
N1024
N1024
N1024
N1024
256
1024
1024
1024
N1024
N1024
N1024
N1024
32
143.52
221.38
164.28
125.48
152.12
86.24
92.15
22.41
141.56
4.02
212.04
8
N1024
128
64
512
4
18.12
156.41
5.24
28.10
N1024
N1024
N1024
N1024
N1024
N1024
N256
4.82
N256
N1024
N1024
118.21
N256

Z. Tang et al. / Fitoterapia 106 (2015) 41–45
45
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shown in Table 3, noted that all compounds could inhibit the prolifera-
tion of cells. PO exhibited significant cytotoxic activity against A549,
A2780, MCF-10, and MFC with IC50 values range from 48.24 to
62.16 mg/L. A8 (IC50 range from 18.12 to 28.10 mg/L) showed a strong
activity against four cell lines. Moreover, A10 (IC50 range from 4.02 to
5.41 mg/L) exhibited the strongest cytotoxic activities against all the
tested cell lines, while the IC50 values of the positive control (cisplatin)
were range from 10.21 to 21.04 mg/L. Thus, A10 showed a stronger in-
hibition of proliferation in the four cell lines than cisplatin, and may
have considerable prospects in the antineoplastic application. This find-
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4. Conclusion
The above results on antibacterial activity of PO and its analogues,
from the structure-effect relationship perspective, prompted us that
the antibacterial activity was related to the function group and its
length, which chaining from 3′ position of the pyranoid ketone ring.
When a number of function groups were 3 carbon–carbon double
bonds (A5), the compound showed a strong antibacterial activity.
Especially, when the function group chaining with electron withdraw-
ing group (A8 and A10), the compound would have a stronger antibac-
terial activity than not. However, when the function group chaining
with electron donating group (A6, A9 and A11), the activity was
vanished. We found that the cytotoxic activity was very strong, when
the compound contain halogen atom (A8 and A10). Taken together,
the pogostone analogues, with proper structure modification, may
develop as a series of novel anticancer or antibacterial agents.
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Conflict of interest statement
pogostone, Chin Med J (Engl) 127 (23) (2014) 40001–40005.
[21] X. Yang, X. Zhang, S.P. Yang, W.Q. Liu, Evaluation of antibacterial activity of Pathouli
oil, Iran. J. Pharm. Res. 12 (3) (2013) 307–316.
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activity and pharmacokinetics of pogostone isolated from Pogostemonis Herba,
Phytomedicine 20 (1) (2012) 77–83.
The authors declare that there are no conflicts of interest.
Acknowledgments
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administration by GC/MS, J. Chromatogr. Sci. 5 (2) (2014) 76–78.
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Violapyrones H and I, new cytotoxic compounds isolated from Streptomyces sp.
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3283–3291.
This work was supported by grant no. 2012JY0114 from the Techno-
logical Office of SiChuan Province. The authors deeply appreciated
associate professor Bo Han for the assistance of synthesis, and Min Dai
for the determination of MIC and MBC.
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