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Argentum 5-Hydroxy-7-methoxy-2-phenyl- 4H-chromen-4-one-6-sulfonate: Synthesis, Crystal Structure and Antitumor Activity

Wu-Wu LI ,  Min-Yan ZHENG ,  Yi-Hong GAO ,  Zun-Ting ZHANG

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Citation:  Wu-Wu LI, Min-Yan ZHENG, Yi-Hong GAO, Zun-Ting ZHANG. Argentum 5-Hydroxy-7-methoxy-2-phenyl- 4H-chromen-4-one-6-sulfonate: Synthesis, Crystal Structure and Antitumor Activity[J]. Chinese Journal of Structural Chemistry, 2020, 39(10): 1898-1905. doi: 10.14102/j.cnki.0254–5861.2011–2791 shu

Argentum 5-Hydroxy-7-methoxy-2-phenyl- 4H-chromen-4-one-6-sulfonate: Synthesis, Crystal Structure and Antitumor Activity

English

  • 1. INTRODUCTION

    Flavonoids are the largest and most important group of natural polyphenolic compounds commonly found in fruits and vegetables[1, 2]. It is classified as flavonols, dihydro- flavones, flavans, isoflavones, chalcones, etc. Flavonoids especially display a wide range of pharmacological properties including anti-inflammatory[3], antiviral[4] and antitumor[5, 6]. Several studies have reported that some flavonoids have direct effects on apoptosis in cancer cell. Luteolin(3΄, 4΄, 5, 7-tetrahy- droxyflavone), a type flavonoid, has effects on apoptosis of colon cancer cells[7]. Another flavonoid, chrysin(5, 7-dihy- droxyflavone), is demonstrated to exert antitumor effect by inducing cell cycle arrest and apoptosis through different mechanisms, for instance, activation of extrinsic apoptosis pathway[8] and alteration of cyclins and CDKs (cyclin- dependent kinases)[9]. 5-Hydroxy-7-methoxyflavone, another flavonoid compound, one of the major flavonoids of pro- polis[10], is contained in many plants, especially in some edible plants such as Alpinia oxyphylla Miquel, Kaempferia parviflora (Zingiberaceae)[11], Alpinia xyphylla (Zingi- beraceae)[12], Muntingia calabura (Tiliaceae)[13], and Carya genus (Juglandaceae)[14], whose fruits, rhizomes or leaves have been traditionally used for local foods and folk medicines[15]. It is known to exhibit a wide range of biological properties. It exhibited a lower intrinsic cytotoxicity than GF120918 (Elacridar) and was apparently not transported by ABCG2 (breast cancer resistance protein). 5-Hydroxy- 7-methoxyflavone therefore constitutes new and promising inhibitors for the reversal of ABCG2-mediated drug transport[16]. In addition, previous researches have found that 5-hydroxy-7-methoxyflavone leads to apoptotic cell death in NSCLC cells through the activation of DR3 and Fas expression via the inhibition of STAT3 phosphorylation[17]. Subsequently, a finding suggested that 5-hydroxy-7- methoxyflavone leads to apoptotic cell death in colon cancer cells through the activation of death receptors expression via the inhibition of NF-κB, so 5-hydroxy-7-methoxyflavone can be a useful agent for the treatment of colon cancer cell growth as well as an adjuvant agent for chemo-resistant cancer cells growth[18]. Recently, 5-hydroxy-7-methoxyflavone decreases the phosphorylation level of ERK and subsequently suppresses activator protein-1 (AP-1) activation to reduce proinflammatory mediator production, suggesting that it has great potential for use in a nutritional preventive strategy against inflammation-related diseases[19]. 5-Hydroxy-7- methoxyflavone is a polycyclic compound, its fat solubility is high, but its solubility in water is very poor. The water solubility of drug is a prerequisite for oral absorption and is a necessary condition for the drug to penetrate cells. Oral drugs absorbed by gastrointestinal mucosa should be in a highly dispersed state. The important significance of drug's water solubility is to disperse the drug components[20]. In order to improve the water solubility of drugs, the introduction of water-soluble groups on the molecular skeleton is expected to improve drug metabolism and increase drug efficacy. As we all know, water solubility of sulfo group is very high. Based on the above considerations, in this work, we introduce the sulfo group into 5-hydroxy-7-methoxyflavone, successfully obtaining sodium 5-hydroxy-7-methoxy-2-phenyl-4H-chro- men-4-one-6-sulfonate. 5-Hydroxy-7-methoxy-2-phenyl-4H- chromen-4-one-6-sulfonate reacts with Ag(I) ions, obtaining a new coordination compound argentum 5-hydroxy-7- methoxy-2-phenyl-4H-chromen-4-one-6-sulfonate, namely [Ag4(H2O)6](C16H11O4SO3)4·H2O (1, C16H11O4SO3 = 5-hy- droxy-7-methoxy-2-phenyl-4H-chromen-4-one-6-sulfonate). 1 exhibits organic-inorganic hybrid framework and a 3D supramolecular architecture. The in vitro antitumor activity investigations show that 1 exhibits inhibitory activity against tumour cell U937 and MCF-7.

    2. EXPERIMENTAL

    2.1 Materials and physical measurements

    Reactions were monitored by thin layer chromatography using UV light to visualize the course of reaction. Purification of reaction products was carried out by recrystallization. Chemical yields referred to pure isolated substances. Elemental analyses (C and H) were determined with an elemental Vairo EL III analyzer. Infrared spectra using the KBr pellets were measured on a Nicolet 6700 FT-IR spectrometer in the range of 400~4000 cm-1. Single-crystal X-ray diffraction was carried out by a Bruker Smart-1000 CCD diffractometer.

    2.2 Synthesis of [Ag4(H2O)6](C16H11O4SO3)4·H2O (1)

    5-Hydroxy-7-methoxyflavone (2.0 g, 7.5 mmol) was put into a 50 mL round-bottomed flask, to which concentrated H2SO4 (12 mL, 225 mmol) was added. The resulting reaction mixture was stirred at room temperature for 15 h monitored by thin-layer chromatography (TLC) which showed the disappearance of 5-hydroxy-7-methoxyflavone indicative of the completeness of the reaction. The reaction mixture was poured into 50 mL distilled water containing 18.0 g sodium chloride, and a yellow precipitate appeared. Then, this precipitate was filtered and washed with saturated sodium chloride solution after standing for 8 h. Finally, sodium 5-hydroxy-7-methoxy-2-phenyl-4H-chromen-4-one-6-sulfonate (Scheme 1) was obtained by recrystallization of the above product in water ethanol-water (V: V = 1:1). The compound was dried in vacuum at 80 ℃ for 5 h with the yield of 75%.

    Scheme 1

    Scheme 1.  Synthetic route for compound 1
    DownLoad: Full-Size Img PowerPoint

    The mixture of sodium 5-hydroxy-7-methoxy-2-phenyl- 4H-chromen-4-one-6-sulfonate (5%, 10 mL) and AgNO3 (10%, 5 mL) was boiled for 30 min under nitrogen atmosphere. After standing for 24 h at room temperature, the mixture was then filtered to obtain argentum 5-hydroxy- 7-methoxy-2-phenyl-4H-chromen-4-one-6-sulfonate (1, yield 58%). Anal. Calcd. for C64H60Ag4O36S4 (1964.87): C, 39.12; H, 3.08%. Found: C, 39.15; H, 3.12%. IR (KBr pellet, cm–1) for 1: 3318(br, vO–H), 1632(vs, vC=O), 1586(s, vph), 1473(s, vph), 1432(s, vph), 1211(m, vC–O), 1156(m, δC–O), 1078(m, vS=O), 1047(m, δS=O), 886(w, δph), 806(w, δph), 756(w, δph), 645(w, δph).

    2.3 X-ray crystallography

    Suitable single crystal of 1 was carefully selected under an optical microscope and glued to thin glass fibers. Structural measurement was performed with a computer-controlled Bruker Smart-1000 CCD diffractometer with graphite-mono- chromated MoKα radiation (λ = 0.71073 Å) at T = 298(2) K. Absorption corrections were made using the SADABS program[21]. The structure was solved by direct methods and refined by full-matrix least-square methods on F2 by using the SHELXL-97 program package[22]. All non-hydrogen atoms were refined anisotropically. The H atoms attached to their parent atoms of organic ligands were geometrically placed and refined using a riding model. Selected bond lengths and bond angles are given in Table 1.

    Table 1

    Table 1.  Selective Geometric Parameters for 1 (Å, °)
    DownLoad: CSV
    Bond Dist. Bond Dist. Bond Dist.
    Ag(1)–O(3)
    Ag(1)–O(4)
    Ag(1)–O(5)
    Ag(1)–O(5)
    Ag(2)–O(3)
    Ag(2)–O(7)
    Ag(2)–O(8)
    Ag(2)–O(9)
    S(1)–O(1)
    S(1)–O(2)
    S(1)–O(3)
    S(1)–C(1)
    S(2)–O(5)    		 2.329(5)
    2.327(7)
    2.378(7)
    2.343(6)
    2.340(6)
    2.386(6)
    2.301(9)
    2.367(10)
    1.437(7)
    1.431(6)
    1.446(5)
    1.759(7)
    1.455(6)    		 S(2)–O(6)
    S(2)–O(7)
    S(2)–C(17)
    O(10)–C(2)
    O(11)–C(4)
    O(12)–C(9)
    O(12)–C(10)
    O(13)–C(6)
    O(13)–C(7)
    C(1)–C(2)
    C(1)–C(9)
    C(2)–C(3)
    C(3)–C(4)    		 1.405(6)
    1.445(5)
    1.756(7)
    1.320(10)
    1.232(11)
    1.340(8)
    1.409(10)
    1.375(9)
    1.363(9)
    1.374(10)
    1.395(11)
    1.413(10)
    1.427(10)    		 C(3)–C(7)
    C(4)–C(5)
    C(5)–C(6)
    C(6)–C(11)
    C(7)–C(8)
    C(8)–C(9)
    C(11)–C(12)
    C(11)–C(16)
    C(12)–C(13)
    C(13)–C(14)
    C(14)–(15)
    C(15)–(16)    		 1.363(11)
    1.424(11)
    1.314(1)
    1.458(11)
    1.385(10)
    1.371(10)
    1.379(12)
    1.356(14)
    1.367(13)
    1.353(18)
    1.368(17)
    1.383(13)
    Angle (º) Angle (º) Angle (º)
    O(3)–Ag(1)–O(5)
    O(3)–Ag(1)–O(5)
    O(4)–Ag(1)–O(3)
    O(4)–Ag(1)–O(5)
    O(4)–Ag(1)–O(5)
    O(5)–Ag(1)–O(5)
    O(3)–Ag(2)–O(7)
    O(1)–S(1)–O(3)
    O(1)–S(1)–C(1)
    O(2)–S(1)–O(1)
    O(2)–S(1)–O(3)
    O(2)–S(1)–C(1)
    O(3)–S(1)–C(1)
    O(6)–S(2)–O(5)
    O(6)–S(2)–O(7)
    O(7)–S(2)–O(5)
    O(7)–S(2)–C(17)
    Ag(1)–O(3)–Ag(2)
    S(1)–O(3)–Ag(1)
    S(1)–O(3)–Ag(2)    		 128.8(2)
    107.1(2)
    103.4(2)
    125.5(2)
    115.6(2)
    76.5(2)
    114.20(19)
    110.9(4)
    105.8(4)
    112.6(5)
    112.2(4)
    105.9(3)
    109.0(3)
    112.5(4)
    113.8(4)
    110.6(4)
    105.3(3)
    104.9(2)
    123.2(3)
    128.0(3)    		 C(2)–C(1)–S(1)
    C(2)–C(1)–C(9)
    C(9)–C(1)–S(1)
    O(10)–C(2)–C(1)
    Ag(1)–O(5)–Ag(1)
    S(2)–O(5)–Ag(1)
    S(2)–O(5)–Ag(1)
    S(2)–O(7)–Ag(2)
    C(9)–O1(2)–C(10)
    C(7)–O(13)–C(6)
    O(10)–C(2)–C(3)
    C(1)–C(2)–C(3)
    C(2)–C(3)–C(4)
    C(7)–C(3)–C(2)
    C(7)–C(3)–C(4)
    O(11)–C(4)–C(3)
    O(11)–C(4)–C(5)
    C(5)–C(4)–C(3)
    C(6)–C(5)–C(4)
    O(13)–C(6)–C(11)    		 115.6(6)
    118.6(7)
    125.3(5)
    120.9(7)
    103.5(2)
    115.4(4)
    140.1(4)
    133.9(4)
    119.2(6)
    118.2(6)
    117.9(7)
    121.2(7)
    122.1(7)
    117.6(7)
    120.2(7)
    121.2(7)
    123.5(7)
    115.2(8)
    122.2(7)
    111.1(7)    		 C(12)–(11)–(6)
    C(16)–(11)–(6)
    C(16)–(11)–(12)
    C(13)–(12)–(11)
    C(5)–(6)–(13)
    C(5)–(6)–(11)
    O(13)–(7)–(3)
    O(13)–C(7)–C(8)
    C(3)–C(7)–C(8)
    C(9)–C(8)–C(7)
    O(12)–C(9)–C(1)
    O(12)–C(9)–C(8)
    C(8)–C(9)–C(1)
    C(14)–C(13)–C(12)
    C(13)–C(14)–C(15)
    C(14)–C(15)–C(16)
    C(11)–C(16)–C(15)
    C(18)–C(17)–S(2)
    C(18)–C(17)–C(25)    		 119.8(9)
    122.2(8)
    117.9(9)
    121.2(11)
    122.1(7)
    26.8(8)
    121.9(7)
    115.3(7)
    122.8(7)
    118.3(7)
    116.8(7)
    121.8(7)
    121.5(6)
    120.2(11)
    119.9(9)
    119.4(11)
    121.4(10)
    122.8(6)
    118.5(6)

    2.4 Test for antitumor activity

    The compounds to be tested were dissolved in DMSO and further diluted to different concentrations by culture medium. The final concentration of DMSO should be controlled in less than 0.01%. The tumor cells U937 and MCF-7 were inoculated in 96-well plates with 5 × 104 cells per well. After incubation for 12 h, different concentrations of compounds to be tested were added to the 96-well plate, with the concentration of each compound to be 2, 4, 8, 16, 32 and 40 μmol/L respectively. The final concentration of DMSO in culture medium should be controlled in less than 0.01%, while no drugs were added to the blank control group, only containing culture medium. Each concentration of the drug and control groups was provided with three multiple wells. After 12 h, cell counting kit-8 (CCK-8) was used to determine the cell viability of U937 and MCF-7, and the 10 μL CCK-8 solution was added to each well plate followed by incubation for 12 h at 37 ℃. The absorbance of each well was detected by automatic microplate reader at 450 nm. The inhibition rate was calculated according to the absorbance value, and the IC50 value of the compound was calculated according to the inhibition rate.

    3. RESULTS AND DISCUSSION

    3.1 Sulfonation reaction

    The poor water solubility of flavonoids can be solved by the attachment of sulfo group on the parent structure. In this respect, there are also many successful examples: salvia miltiorrhiza is a kind of Chinese herbal for invigorating blood circulation and eliminating stasis and its effective component is tanshinone. A finding suggested that the introduction of sulfo group into tanshinone can improve the physiological activity of tanshinone[23, 24]. Inspired by this, we introduce sulfo group into 5-hydroxy-7-methoxyflavone by sulfonation reaction.

    The sulfonation reaction of 5-hydroxy-7-methoxyflavone with concentrated H2SO4 is an electrophilic substitution reaction. The concentrated H2SO4 in the reaction is both sulfonating agent and solvent. Because the protons of H2SO4 can combine with the oxygen atoms of pyran ring to form a cyclic cation (Scheme 2), the flavone is soluble and stable in concentrated H2SO4. Since both oxhydryl and methoxyl on the A ring of flavone skeleton can activate it, the sulfonation reaction can occur at normal temperature.

    Scheme 2

    Scheme 2.  Formation of cyclic cation in 1
    DownLoad: Full-Size Img PowerPoint

    3.2 Description of the crystal structure

    The molecular structure of 1 (Fig. 1) consists of four 5-hydroxy-7-methoxy-2-phenyl-4H-chromen-4-one-6-sulfo- nate anions, two Ag(I) cations, six coordination water molecules and one latticed water molecule. The title structure contains two different flavone skeletons Ske1 (C(1)~C(16)/O(13)) and Ske2 (C(17)~C(32)/O(17)). Benzopyran ring of flavone is essentially planar, with the mean deviation from the mean plane being 0.0345(4) Å for Ske1 and 0.0205(6) Å for Ske2. Because carbon atoms C(6) and C(22) of benzopyran ring are sp2 hybridized carbon, the benzopyran ring is coplanar with benzene ring (ring B), and the dihedral angles between the two rings are 6.653(4)° for Ske1 and 3.731(2)° for Ske2. These values are consistent with literature reports[25]. There are two crystallographically independent Ag(I) atoms, both of which are four-coordinated in similar coordination environments. Ag(1) coordinates with three oxygen atoms of sulfo groups and one oxygen atom of coordination water molecule. Ag(2) coordinates with two oxygen atoms of sulfo groups and two oxygen atoms of coordination water molecules. Ag(I) adopts a distorted AgO4 tetrahedral geometry with O–Ag distance of 2.301(9)~2.386(6) Å. These values are comparable to those reported for Ag(I) complexes[26]. The flavone skeletons exhibit two different coordination fashions. Ske1 involves in coordination in the form of bidentate chelation via O(5) and O(7) of sulfo group, and Ske2 of unidentate chelation via O(3) of sulfo group. Six-membered coordination rings are formed through Ag–O coordination interactions. Adjacent six-membered rings are linked by a pair of Ag(5)–O(1) bonds to form the (6-4-6) fused ring.

    Figure 1

    Figure 1.  Molecular structure of 1. Displacement ellipsoids are drawn at the 30% probability level. The hydrogen atom is omitted for clarity. Symmetry code: (i) 2–x, 1–y, 1–z
    DownLoad: Full-Size Img PowerPoint

    In addition to coordination interactions, the crystal structure is also held together by O–H···O hydrogen bonding inter- actions (Fig. 2). Pertinent geometric parameters of hydrogen- bond and symmetry codes are shown in Table 2. Intra- molecular hydrogen-bonds O(14)–H(14)···O(15) and O(10)–H(10)···O(11) form an S(6) closed pattern. Hydrogen bonds O(8)–H(8B)···O(6) and O(8)–H(8B)···O(14) collecti- vely form a planar three-center hydrogen-bonding configura- tion (Fig. 2a), where the sum of angles (351.5(5)°) about atom O(8) is slightly less than the ideal value 360°[27]. Adjacent molecules are linked by three-center hydrogen bonds to yield a one-dimensional chain running along the a axis. The term three-center hydrogen bond[28] indicates that the H atom is at the center of the three participating donor and acceptor atoms, and indistinguishably refers to both bifurcated donor and acceptor bonds. Latticed water molecules O(18) are both donor of O(18)–H(18A)···O(2) and acceptor of O(4)– H(4A)···O(18) (Fig. 2b). Adjacent molecules are linked by these two hydrogen bonds to yield a one-dimensional chain running along the b axis.

    Figure 2

    Figure 2.  Hydrogen-bond configurations in 1, including the three-center hydrogen-bond configuration. Only relevant flavone skeletons, H atoms and hydrogen bond are shown for clarity. Symmetry codes: (ii) 1–x, 1–y, 1–z; (iii) 2–x, –y, 1–z
    DownLoad: Full-Size Img PowerPoint

    Table 2

    Table 2.  Hydrogen-bond Configuration Parameters for 1
    DownLoad: CSV
    D–H···A d(D–H) d(H···A) d(D···A) DHA
    1 O(8)–H(8B)···O(6)ii
    O(8)–H(8B)···O(14)ii
    O(4)–H(4B)···O(7)ii
    O(14)–H(14)···O(15)
    O(4)–H(4A)···O(18)
    O(18)–H(18A)···O(2)iii
    O(10)–H(10)···O(11)
    O(9)–H(9A)···O(1)iv
    O(9)–H(9B)···O(18)ii
    O(18)–H(18B)···O(1)    		 0.88
    0.88
    0.91
    0.82
    0.90
    0.85
    0.82
    0.85
    0.88
    0.85    		 1.96
    2.60
    1.84
    1.77
    2.00
    2.20
    1.77
    2.28
    1.89
    1.98    		 2.809(10)
    3.167(10)
    2.738(9)
    2.521(7)
    2.895(13)
    2.731(11)
    2.511(9)
    2.969(12)
    2.631(12)
    2.769(9)    		 160
    123
    169
    151
    172
    141
    150
    138
    142
    155
    Symmetry codes: (ii) 1–x, 1–y, 1–z; (iii) 2–x, –y, 1–z; (iv) x, 1+y, z

    Flavone skeletons form the organic region of 1, while O–H···O hydrogen-bonds and Ag–O coordination interactions form the inorganic region. The organic ligands connect adjacent Ag(I) ions to give an organic-inorganic hybrid frame- work (Fig. 3). [Ag4(H2O)6](C16H11O4SO3)4·H2O mole- cules are linked by hydrogen bonds, coordination interactions mentioned above and electrostatic attraction between anion and cation, resulting in a three-dimensional supramolecular architecture in the solid state (Fig. 3).

    Figure 3

    Figure 3.  Packing diagram of 1
    DownLoad: Full-Size Img PowerPoint

    3.3. In vitro antitumor activity

    The in vitro antitumor activities of 1 against human lymphoma cells U937 and human breast cancer cells MCF-7 were evaluated with CCK-8 assay, with procaspase-3 small molecule activators 1541 and 1541B used as positive control drugs. As shown in Table 3, compared with the antitumor activities of the positive control drugs 1541 and 1541B, 1 showed a moderate inhibitory activity against U937 and a relatively weak inhibitory activity against MCF-7. Compared with 5-hydroxy-7-methoxyflavone, inhibitory activities of 1 against human lymphoma cells U937 and human breast cancer cells MCF-7 were stronger, indicating that the intro- duction of sulfo group into the parent structure can increase the anti-tumor activity of the substance.

    Table 3

    Table 3.  Anti-tumor Activities for the Target Compound
    DownLoad: CSV
    Compound IC50/μmol/L a Compound IC50/μmol/L a
    U937 MCF-7 U937 MCF-7
    1 9.4 ± 0.3 22.5 ± 0.3 1541 4.9 ± 0.2 5.5 ± 0.3
    1541B 6.2 ± 0.2 7.5 ± 0.4 PCb 17.4 ± 0.4 28.6 ± 0.2
    a The given value is the average of the three experiments ± SD. b PC represents 5-hydroxy-7-methoxyflavone

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  • Scheme 1  Synthetic route for compound 1

    下载: 全尺寸图片 幻灯片

    Scheme 2  Formation of cyclic cation in 1

    下载: 全尺寸图片 幻灯片

    Figure 1  Molecular structure of 1. Displacement ellipsoids are drawn at the 30% probability level. The hydrogen atom is omitted for clarity. Symmetry code: (i) 2–x, 1–y, 1–z

    下载: 全尺寸图片 幻灯片

    Figure 2  Hydrogen-bond configurations in 1, including the three-center hydrogen-bond configuration. Only relevant flavone skeletons, H atoms and hydrogen bond are shown for clarity. Symmetry codes: (ii) 1–x, 1–y, 1–z; (iii) 2–x, –y, 1–z

    下载: 全尺寸图片 幻灯片

    Figure 3  Packing diagram of 1

    下载: 全尺寸图片 幻灯片

    Table 1.  Selective Geometric Parameters for 1 (Å, °)

    Bond Dist. Bond Dist. Bond Dist.
    Ag(1)–O(3)
    Ag(1)–O(4)
    Ag(1)–O(5)
    Ag(1)–O(5)
    Ag(2)–O(3)
    Ag(2)–O(7)
    Ag(2)–O(8)
    Ag(2)–O(9)
    S(1)–O(1)
    S(1)–O(2)
    S(1)–O(3)
    S(1)–C(1)
    S(2)–O(5)    		 2.329(5)
    2.327(7)
    2.378(7)
    2.343(6)
    2.340(6)
    2.386(6)
    2.301(9)
    2.367(10)
    1.437(7)
    1.431(6)
    1.446(5)
    1.759(7)
    1.455(6)    		 S(2)–O(6)
    S(2)–O(7)
    S(2)–C(17)
    O(10)–C(2)
    O(11)–C(4)
    O(12)–C(9)
    O(12)–C(10)
    O(13)–C(6)
    O(13)–C(7)
    C(1)–C(2)
    C(1)–C(9)
    C(2)–C(3)
    C(3)–C(4)    		 1.405(6)
    1.445(5)
    1.756(7)
    1.320(10)
    1.232(11)
    1.340(8)
    1.409(10)
    1.375(9)
    1.363(9)
    1.374(10)
    1.395(11)
    1.413(10)
    1.427(10)    		 C(3)–C(7)
    C(4)–C(5)
    C(5)–C(6)
    C(6)–C(11)
    C(7)–C(8)
    C(8)–C(9)
    C(11)–C(12)
    C(11)–C(16)
    C(12)–C(13)
    C(13)–C(14)
    C(14)–(15)
    C(15)–(16)    		 1.363(11)
    1.424(11)
    1.314(1)
    1.458(11)
    1.385(10)
    1.371(10)
    1.379(12)
    1.356(14)
    1.367(13)
    1.353(18)
    1.368(17)
    1.383(13)
    Angle (º) Angle (º) Angle (º)
    O(3)–Ag(1)–O(5)
    O(3)–Ag(1)–O(5)
    O(4)–Ag(1)–O(3)
    O(4)–Ag(1)–O(5)
    O(4)–Ag(1)–O(5)
    O(5)–Ag(1)–O(5)
    O(3)–Ag(2)–O(7)
    O(1)–S(1)–O(3)
    O(1)–S(1)–C(1)
    O(2)–S(1)–O(1)
    O(2)–S(1)–O(3)
    O(2)–S(1)–C(1)
    O(3)–S(1)–C(1)
    O(6)–S(2)–O(5)
    O(6)–S(2)–O(7)
    O(7)–S(2)–O(5)
    O(7)–S(2)–C(17)
    Ag(1)–O(3)–Ag(2)
    S(1)–O(3)–Ag(1)
    S(1)–O(3)–Ag(2)    		 128.8(2)
    107.1(2)
    103.4(2)
    125.5(2)
    115.6(2)
    76.5(2)
    114.20(19)
    110.9(4)
    105.8(4)
    112.6(5)
    112.2(4)
    105.9(3)
    109.0(3)
    112.5(4)
    113.8(4)
    110.6(4)
    105.3(3)
    104.9(2)
    123.2(3)
    128.0(3)    		 C(2)–C(1)–S(1)
    C(2)–C(1)–C(9)
    C(9)–C(1)–S(1)
    O(10)–C(2)–C(1)
    Ag(1)–O(5)–Ag(1)
    S(2)–O(5)–Ag(1)
    S(2)–O(5)–Ag(1)
    S(2)–O(7)–Ag(2)
    C(9)–O1(2)–C(10)
    C(7)–O(13)–C(6)
    O(10)–C(2)–C(3)
    C(1)–C(2)–C(3)
    C(2)–C(3)–C(4)
    C(7)–C(3)–C(2)
    C(7)–C(3)–C(4)
    O(11)–C(4)–C(3)
    O(11)–C(4)–C(5)
    C(5)–C(4)–C(3)
    C(6)–C(5)–C(4)
    O(13)–C(6)–C(11)    		 115.6(6)
    118.6(7)
    125.3(5)
    120.9(7)
    103.5(2)
    115.4(4)
    140.1(4)
    133.9(4)
    119.2(6)
    118.2(6)
    117.9(7)
    121.2(7)
    122.1(7)
    117.6(7)
    120.2(7)
    121.2(7)
    123.5(7)
    115.2(8)
    122.2(7)
    111.1(7)    		 C(12)–(11)–(6)
    C(16)–(11)–(6)
    C(16)–(11)–(12)
    C(13)–(12)–(11)
    C(5)–(6)–(13)
    C(5)–(6)–(11)
    O(13)–(7)–(3)
    O(13)–C(7)–C(8)
    C(3)–C(7)–C(8)
    C(9)–C(8)–C(7)
    O(12)–C(9)–C(1)
    O(12)–C(9)–C(8)
    C(8)–C(9)–C(1)
    C(14)–C(13)–C(12)
    C(13)–C(14)–C(15)
    C(14)–C(15)–C(16)
    C(11)–C(16)–C(15)
    C(18)–C(17)–S(2)
    C(18)–C(17)–C(25)    		 119.8(9)
    122.2(8)
    117.9(9)
    121.2(11)
    122.1(7)
    26.8(8)
    121.9(7)
    115.3(7)
    122.8(7)
    118.3(7)
    116.8(7)
    121.8(7)
    121.5(6)
    120.2(11)
    119.9(9)
    119.4(11)
    121.4(10)
    122.8(6)
    118.5(6)
    下载: 导出CSV

    Table 2.  Hydrogen-bond Configuration Parameters for 1

    D–H···A d(D–H) d(H···A) d(D···A) DHA
    1 O(8)–H(8B)···O(6)ii
    O(8)–H(8B)···O(14)ii
    O(4)–H(4B)···O(7)ii
    O(14)–H(14)···O(15)
    O(4)–H(4A)···O(18)
    O(18)–H(18A)···O(2)iii
    O(10)–H(10)···O(11)
    O(9)–H(9A)···O(1)iv
    O(9)–H(9B)···O(18)ii
    O(18)–H(18B)···O(1)    		 0.88
    0.88
    0.91
    0.82
    0.90
    0.85
    0.82
    0.85
    0.88
    0.85    		 1.96
    2.60
    1.84
    1.77
    2.00
    2.20
    1.77
    2.28
    1.89
    1.98    		 2.809(10)
    3.167(10)
    2.738(9)
    2.521(7)
    2.895(13)
    2.731(11)
    2.511(9)
    2.969(12)
    2.631(12)
    2.769(9)    		 160
    123
    169
    151
    172
    141
    150
    138
    142
    155
    Symmetry codes: (ii) 1–x, 1–y, 1–z; (iii) 2–x, –y, 1–z; (iv) x, 1+y, z
    下载: 导出CSV

    Table 3.  Anti-tumor Activities for the Target Compound

    Compound IC50/μmol/L a Compound IC50/μmol/L a
    U937 MCF-7 U937 MCF-7
    1 9.4 ± 0.3 22.5 ± 0.3 1541 4.9 ± 0.2 5.5 ± 0.3
    1541B 6.2 ± 0.2 7.5 ± 0.4 PCb 17.4 ± 0.4 28.6 ± 0.2
    a The given value is the average of the three experiments ± SD. b PC represents 5-hydroxy-7-methoxyflavone
    下载: 导出CSV
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  • 发布日期:  2020-10-01
  • 收稿日期:  2020-03-02
  • 接受日期:  2020-04-27
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