This article was downloaded by: [Purdue University]On: 31 August 2014, At: 19:32Publisher: Taylor & FrancisInforma Ltd Registered in England and Wales Registered Number: 1072954 Registeredoffice: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK

Phosphorus, Sulfur, and Silicon and theRelated ElementsPublication details, including instructions for authors andsubscription information:http://www.tandfonline.com/loi/gpss20

Synthesis, Antitumor Activity, and SARof N-Substituted γ-AminopropylsilatraneDerivativesGuo Ping a , Wang Yue-Wu a , Luo Xin-Tong a , Qi Xiao-Lu a , Hou Le-Ping a , Xie Zi-Xin a & Ye Fa-Qing aa School of Pharmacy, Wenzhou Medical College , Wenzhou ,Zhejiang , 325035 , P. R. ChinaAccepted author version posted online: 23 Sep 2013.Publishedonline: 12 Mar 2014.

To cite this article: Guo Ping , Wang Yue-Wu , Luo Xin-Tong , Qi Xiao-Lu , Hou Le-Ping , Xie Zi-Xin &Ye Fa-Qing (2014) Synthesis, Antitumor Activity, and SAR of N-Substituted γ-AminopropylsilatraneDerivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 189:4, 511-518, DOI:10.1080/10426507.2013.829835

To link to this article: http://dx.doi.org/10.1080/10426507.2013.829835

PLEASE SCROLL DOWN FOR ARTICLE

Taylor & Francis makes every effort to ensure the accuracy of all the information (the“Content”) contained in the publications on our platform. However, Taylor & Francis,our agents, and our licensors make no representations or warranties whatsoever as tothe accuracy, completeness, or suitability for any purpose of the Content. Any opinionsand views expressed in this publication are the opinions and views of the authors,and are not the views of or endorsed by Taylor & Francis. The accuracy of the Contentshould not be relied upon and should be independently verified with primary sourcesof information. Taylor and Francis shall not be liable for any losses, actions, claims,proceedings, demands, costs, expenses, damages, and other liabilities whatsoever orhowsoever caused arising directly or indirectly in connection with, in relation to or arisingout of the use of the Content.

This article may be used for research, teaching, and private study purposes. Anysubstantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions

Dow

nloa

ded

by [

Purd

ue U

nive

rsity

] at

19:

32 3

1 A

ugus

t 201

4

Phosphorus, Sulfur, and Silicon, 189:511–518, 2014Copyright C© Taylor & Francis Group, LLCISSN: 1042-6507 print / 1563-5325 onlineDOI: 10.1080/10426507.2013.829835

THE SYNTHESIS, ANTITUMOR ACTIVITY, AND SAR OFN-SUBSTITUTED γ -AMINOPROPYLSILATRANEDERIVATIVES

Guo Ping, Wang Yue-Wu, Luo Xin-Tong, Qi Xiao-Lu, HouLe-Ping, Xie Zi-Xin, and Ye Fa-QingSchool of Pharmacy, Wenzhou Medical College, Wenzhou, Zhejiang 325035,P. R. China

GRAPHICAL ABSTRACT

Abstract γ -Aminopropylsilatrane has been reported to possess biological activity againsttumor cancer cells with low cytotoxicity in many kinds of silatranes. So some N-substitutedγ -aminopropylsilatrane derivatives were synthesized and assayed by a primary anticancerscreening against HT-29, Hela, and MDAMB435 cells by the use of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The structures of these derivatives wereconfirmed by 1H NMR, electrospray ionization-mass spectrometry, and elemental analysis. Thestructure–activity relationship showed that the N-substituted derivatives exhibit better activityin which the γ -amino group of the silatrane is connected with stronger electron-withdrawinggroups.

Keywords γ -Aminopropylsilatrane derivatives; structure–activity relationship (SAR); physi-ological activity

Received 13 May 2013; accepted 1 July 2013.Address correspondence to Dr Guo Ping, School of Pharmacy, Wenzhou Medical College; Wenzhou,

Zhejiang 325035, P. R. China. E-mail: gp 0713@163.com

511

Dow

nloa

ded

by [

Purd

ue U

nive

rsity

] at

19:

32 3

1 A

ugus

t 201

4

512 G. PING ET AL.

INTRODUCTION

Silatranes, heterotricyclic compounds exhibiting an intramolecular transannular da-tive Si←N bond, are challenging targets for scientists from the point of view of theirstructural features and applications. The strength of the dative bond depends not only onthe substituent on the silicon but also on the skeletal structure of the parent ring. Thelength of this bond is also influenced by the position, axial or equatorial, occupied by thesubstituent on the silicon as well as by cage effects.1–4 The analysis of the electron densitydistribution in the silatrane led to the conclusion that obviously the interaction betweennitrogen and silicon is rather electrostatic and less covalent. Therefore, they are relativelystable to moisture, and more difficult to hydrolyze compared with their analogs (trialkoxysi-lanes) and can be used in various reactions, e.g., additions and nucleophilic substitutions.5–8

Optimization of the 1-substituted groups is important since the toxicity and bioactivity ofsilatranes is correlated with these groups.

Many derivatives of silatrane could even stimulate the biosynthesis of nucleic acidsand proteins and the growth of some cells, especially regenerating cells of connective tissueand liver.9–11 But some 1-arylsilatranes were almost twice as toxic as well-known poisonsas strychnine and hydrocyanic acid. Meanwhile, 1-alkyl- or 1-alkoxysilatranes did notinfluence the growth of normal cells even in a higher concentration. In 1-alkyl derivatives, γ -aminopropylsilatranes (Figure 1, R=CH3) has captured high interest due to their bioactivity,safety, and potential for the preparation of new silatranes by derivatization of the aminogroup. They are also an important group of biologically active compounds as a result oftheir diverse pharmacological applications, such as antitumor,12 antiviral,13,14 and regulatingplant growth.8 At the same time, it was found that γ -aminopropylsilatrane is capable ofenhancing the carcinostatic effect of the well-known antitumor drug cyclophosphamide.13,15

Recently, silatranes were shown to exhibit pronounced antitumor activity by reducing theability of tumor cells to undergo invasion and by inhibiting tumor growth. Inaddition,silatranes adorned with methyl groups (Figure 1, R=CH3) have the advantage of being morestable toward hydrolysis, whereas those without (Figure 1, R=H) may have an advantagein terms of inhibiting an enzyme because the active site should better accommodate theless bulky ligands.12

To get a better understanding of the structure–activity relationship (SAR) in thistype of compounds by modifications in the γ -amino groups of silatrane, we report here

Figure 1 Structure of γ -aminopropylsilatrane.

Dow

nloa

ded

by [

Purd

ue U

nive

rsity

] at

19:

32 3

1 A

ugus

t 201

4

SYNTHESIS, ANTITUMOR ACTIVITY, AND SAR OF N-SUBSTITUTED 513

the synthesis and biological activity of compounds derived from γ -aminopropylsilatraneand γ -aminopropyl-3,7,10-trimethylsilatrane. By use of various aroyl chlorides, aldehy-des, and isocyanates for reactions with the γ -amino group, numerous N-substituted γ -aminopropylsilatranes were synthesized and their action in vitro against HT-29, Hela, andMDAMB435 was investigated. Because γ -aminopropylsilatrane could improve the effectof antitumor drugs, its mutual prodrugs were designed and synthesized. A clinical antitu-mor drug 5-fluorouracil (5-FU), but not cyclophosphamide, was selected to introduce intothe mutual prodrugs due to better reactive properties and lesser molecular weight. Finally,some N-substituted γ -aminopropylsilatrane derivatives containing the structure of 5-FUwere synthesized and assayed to check their synergism.

RESULTS AND DISCUSSION

Our strategy for the synthesis of derivatives with different structures was based ona nucleophilic addition reaction between silatrane and aromatic acid chlorides, aromaticaldehydes, aromatic isocyanates, and 5-FU. Thirty-two compounds (2a–j, 3a–i, 4a–i, 5a–b,

Figure 2 Synthesis of diverse N-substituted γ -aminopropylsilatranes. Regents and conditions: (i) CHCl3, dif-ferent alkyl chlorides, NEt3, rt., 2 h; (ii) benzene, aromatic aldehydes, reflux, 2 h; (iii) toluene, NEt3, aromaticisocyanate, reflux, 2 h; (iv) N2, CHCl3, NEt3, 2–3 h; (v) DMF, DCC, rt., 2–3 h.

Dow

nloa

ded

by [

Purd

ue U

nive

rsity

] at

19:

32 3

1 A

ugus

t 201

4

514 G. PING ET AL.

Table 1 The inhibitory activities of the tested compounds

IC50 (μg/mL)Compound MDAMB435 Hela HT29

5-FU 9.66 10.1 6.221a >100 >100 89.31b 77.4 >100 86.82a 69.3 >100 77.42b 33.1 >100 29.02c 36.3 >100 30.42d 57.5 >100 44.32e 61.4 >100 50.82f 35.6 >100 28.92g 77.3 >100 50.12h 96.2 >100 84.92i >100 >100 80.02j 40.6 >100 62.53a 25.3 22.4 27.33b 32.7 30.0 32.83c 29.0 30.9 25.13d 24.6 27.1 28.33e 19.2 24.9 20.03f 15.7 18.3 15.23g 14.9 11.1 15.93h 14.9 14.15 15.83i 12.5 11.8 12.34a 87.7 >100 70.64b 85.8 >100 63.14c 35.4 >100 32.34d 76.6 >100 47.54e 69.5 >100 45.94f 90.0 >100 57.74g >100 >100 95.64h >100 >100 87.74i >100 >100 80.65a 20.6 18.7 25.25b 17.1 13.3 11.66a 22.5 31.2 14.96b 15.7 35.6 18.2

6a–b) exhibiting the framework of γ -aminopropylsilatrane (1a and 1b) were designedand synthesized. Their chemical structures are shown in Figure 2. Initially, 2a–j weresynthesized by the reaction of 1a–b with various aroyl chlorides, 3a–i were synthesized bythe reaction of 1a–b with aldehydes, 4a–i were synthesized by the reaction of 1a–b withisocyanates, and 5a–b and 6a–b were synthesized by linking 1a–b with 5-FU via differentchemical bridges.

For the primary assay, the percentage inhibitions of compounds at 0.4, 2, 10, 50,and 100 μg/mL were measured against HT-29, Hela, MDAMB435 respectively in vitro incomparison with 5-FU. Then we determined their IC50 values by SPSS.

From the results listed in Table 1, one can see that all target compounds are weakerthan 5-FU in the inhibition of tumor cell growth. In contrast, the performance of compounds5a–b and 6a–b is quite good, and is very close to 5-FU. Next, 3a–i is better than 4a–i.

Dow

nloa

ded

by [

Purd

ue U

nive

rsity

] at

19:

32 3

1 A

ugus

t 201

4

SYNTHESIS, ANTITUMOR ACTIVITY, AND SAR OF N-SUBSTITUTED 515

CONCLUSIONS

Thirty-two N-substituted γ -aminopropylsilatranes were synthesized and tested fortheir activities on HT-29, Hela, and MDAMB435.

Different types of products exhibit their own selectivity. For example, 1a–b, 2d–j, and4a–i had no activity to Hela cells. The 3,7,10-trimethyl derivatives derived from 1b weremore active than those without methyl substituents (derived from 1a). 2a and 2f showed ahigher antitumor activity than 2i and 2j respectively.

Since 3a–i exhibited good performance to three types of cancer cells, obviously,the C=N double bond plays a critical role. On the other hand, a two-fold increase in theinhibitory activity of both MDAMB435 and HT-29 assays was observed when the N atomwas substituted by a strong electron-withdrawing group, e.g., 2b and 4c showed morepreferable bioactivity than 2e and 4f respectively.

To check the synergism between the γ -aminopropylsilatrane and 5-FU, we linkedthese moieties together. However, the activity of 5a–b and 6a–b was still slightly lowercompared with 5-FU. This could be due to the amide linkage, which can rarely be cleavedin culture cells that block their synergism.

The SAR analysis indicates that the N-substituted γ -aminopropylsilatranes were welloptimized for bioactivity via appropriate chemical modification.

EXPERIMENTAL

Instruments and Reagents

Uncorrected melting points (m.p.) were determined using an XRC-1 micro-meltingpoint apparatus. Thin layer chromatography (TLC, Rf values) was performed on F254 orsilica gel plates F254 (0.2-mm thick) and visualization was effected with UV light. 1HNMR spectra were recorded on a Bruker Avance-3600 spectrometer (600 MHz). Sampleswere dissolved in CDCl3, while tetramethylsilane (TMS) was used as an internal standard.Chemical shifts δ were recorded in ppm relative to TMS, and J-values are expressed in Hz.Mass spectra (MS) were recorded using an Agilent-1100 LC mass spectrometer.

General Procedure for the Preparation of 1a–b

The γ -aminopropylsilatranes 1a and 1b were synthesized by condensation of triiso-propanolamine or triethylolamine with γ -aminopropyltriethoxysilane. The products wereobtained by vacuum distillation. For the data of 1a and 1b see Dumitriu et al.6

General Procedure for the Preparation of 2a–j

Different chlorides (0.012 mol) were added drop-wise to a solution of 1a/1b(0.01 mol) in CHCl3 (10 mL) containing triethylamine (2 mL). The solution was stirred atroom temperature for 2 h. The filtrate was washed twice with NaHCO3 (0.6 mol/L). Theorganic layer was dried with Na2SO4 and then dumped into petroleum ether. The products2a–j precipitated as white solids. They were purified by further recrystallization. 2e, 2f,2h, and 2j have not been reported before. For the data of 2a–d, see Hu et al.16

[γ -(4-Methylbenzoylamino]propyl-3,7,10-trimethylsilatrane (2e). M.p.:139–140◦C; 1H NMR: 0.22–0.49 (m, 2H, H-α), 1.05–1.50 (m, 9H, CH3–3,7,10), 1.51–1.82(m, 2H, H-β), 2.02–2.33 (m, 2H, H-γ ), 2.35 (s, 3H, Ph-CH3), 2.62–3.28 (m, 6H, H-4,6,11),

Dow

nloa

ded

by [

Purd

ue U

nive

rsity

] at

19:

32 3

1 A

ugus

t 201

4

516 G. PING ET AL.

3.85–4.20 (m, 3H, H-3,7,10), 6.69 (br, 1H, NH), 7.32 (d, 2H, J = 8.4, Ph-H), 7.84 (d, 2H,J = 8.4, Ph-H). ESI-MS: 393 [M+H]+. Calcd. for C20H32N2O4Si: C, 61.19; H, 8.22; N,7.14; Si, 7.14%. Found: C, 61.08; H, 8.21; N, 7.15; Si, 7.21%.

[γ -(2-Fluorobenzoyl)Amino]Propyl-3,7,10-Trimethylsilatrane (2f). M.p.:152–153◦C; 1H NMR: 0.20–0.55 (m, 2H, H-α), 1.00–1.55 (m, 9H, CH3–3,7,10), 1.60–1.87(m, 2H, H-β), 2.23–2.55 (m, 2H, H-γ ), 2.75–3.45 (m, 6H, H-4,6,11), 3.85–4.19 (m, 3H,H-3,7,10), 7.04 (br, 1H, NH), 7.47–7.86(m, 4H, Ph-H). ESI-MS: 397 [M+H]+. Calcd. forC19H29FN2O4Si: C, 57.55; H, 7.37; N, 7.06; Si, 7.06%. Found: C, 56.99; H, 7.35; N, 7.01;Si, 6.98%.

[γ -(4-Methylbenzoyl)amino]propylsilatrane (2h). M.p.: 168–169◦C; 1HNMR: 0.23–0.45 (m, 2H, H-α), 1.65–1.85 (m, 2H, H-β), 2.47–2.69 (m, 2H, H-γ ), 2.52(s, 3H, PhCH3), 2.65–3.40 (m, 6H, H-4,6,11), 3.75–4.13 (m, 6H, H-3,7,10), 6.71 (br, 1H,NH), 7.70 (d, 2H, J = 8.4, Ph-H), 8.42 (d, 2H, J = 8.4, Ph-H). ESI-MS: 351 [M+H]+.Calcd. for C17H26N2O4Si: C, 58.26; H, 7.48; N, 7.99; Si, 7.99%. Found: C, 58.11; H, 7.50;N, 7.81; Si, 7.80%.

[γ -(2-Fluorobenzoyl)amino]propylsilatrane (2j). M.p.: 170–171◦C; 1HNMR: 0.23–0.50 (m, 2H, H-α), 1.45–1.87 (m, 2H, H-β), 2.52–2.65 (m, 2H, H-γ ),2.65–3.38 (m, 6H, H-4,6,11), 3.72–3.87 (m, 6H, H-3,7,10), 6.96 (br, 1H, NH), 7.30–7.76(m, 4H, Ph-H). ESI-MS: 355 [M+H]+. Calcd. for C16H23FN2O4Si: C, 54.22; H, 6.54; N,7.90; Si, 7.92, F, 5.36%. Found: C, 54.89; H, 6.77; N, 7.80; Si, 7.50, F, 5.44%.

General Procedure for the Preparation of 3a–j

0.01 Mol 1a or 1b was dissolved in 20 mL benzene. Then the aromatic aldehyde(0.01 mol) was added. A water separator was installed in order to remove the by-productwater and to accelerate the reaction. The mixture was stirred and refluxed for 2 h. Benzeneand water were removed under reduced pressure, and the residue was recrystallized frombenzene and ether. We have synthesized 3a–j previously.8

General Procedure for the Preparation of 4a–j

Compound 1a or 1b, 0.01 mol, was added to the stirred solution of toluene, anddissolved. Then the aromatic isocyanate (0.01 mol) was added. The mixture was stirredand refluxed for 0.5 h. Compounds 4a–j and 2a–j were isolated from the mixture. Com-pounds 4e, 4f, 4h, and 4i have not been described before. For the data of 4a-d, seeHu et al.16

N′-(3-Chlorophenyl)-γ -ureidopropyl-3,7,10-trimethylsilatrane (4e). M.p.:151–152◦C. 1H NMR: 0.28–0.49 (m, 2H, H-α), 1.20–1.32(m, 9H, CH3–3,7,10), 1.65–1.76(m, 2H, H-β), 2.20–2.35 (m, 2H, H-γ ), 2.85–3.30 (m, 6H, H-4,6,11), 3.82–4.15 (m, 3H,H-3,7,10), 5.18 (br, 1H, NH), 6.16 (br, 1H, NH), 7.08–7.20 (m, 4H, Ph-H). ESI-MS: 428[M+H]+. Calcd. for C19H30ClN3O4Si: C, 53.32; H, 7.06; N, 9.82; Si, 6.55%. Found: C,53.08; H, 7.12; N, 9.87; Si, 6.75%.

N′-(4-Methylphenyl)-γ -ureidopropyl-3,7,10-trimethylsilatrane (4f). M.p.:197–198◦C. 1H NMR: 0.25–0.45 (m, 2H, H-α), 1.19–1.33 (m, 9H, CH3–3,7,10), 1.56–1.87(m, 2H, H-β), 2.10–2.30 (m, 2H, H-γ ), 2.41 (s, 3H, PhCH3), 2.60–3.31 (m, 6H, H-4,6,11),3.76–4.19 (m, 3H, H-3,7,10), 5.23 (br, 1H, NH), 6.58 (br, 1H, NH), 7.21 (d, 2H, J = 8.4,Ph-H), 7.28 (d, 2H, J = 8.4, Ph-H). ESI-MS: 408 [M+H]+. Calcd. for C20H33N3O4Si:

Dow

nloa

ded

by [

Purd

ue U

nive

rsity

] at

19:

32 3

1 A

ugus

t 201

4

SYNTHESIS, ANTITUMOR ACTIVITY, AND SAR OF N-SUBSTITUTED 517

C, 58.94; H, 8.16; N, 10.31; Si, 6.88%. Found: C, 58.88; H, 8.20; N, 10.30; Si,6.89%.

N′-(4-Methylphenyl)-γ -ureidopropylsilatrane (4h). M.p.: 196–197◦C. 1HNMR: 0.26–0.47 (m, 2H, H-α), 1.15–1.35 (m, 2H, H-β), 2.15–2.60 (m, 2H, H-γ ),2.65–3.40 (m, 6H, H-4,6,11), 3.57 (s, 3H, PhCH3), 3.70–3.83 (m, 6H, H-3,7,10), 5.25 (br,1H, NH), 6.47 (br, 1H, NH), 7.88 (d, 2H, J = 8.4, Ph-H), 8.56 (d, 2H, J = 8.4, Ph-H).ESI-MS: 366 [M+H]+. Calcd. for C17H27N3O4Si: C, 55.86; H, 7.45; N, 11.50; Si, 7.67%.Found: C, 55.78; H, 7.49; N, 11.49; Si, 7.80%.

N′-(3-Methylphenyl)-γ -uureidopropylsilatrane (4i). M.p.: 148–149◦C. 1HNMR: 0.26–0.44 (m, 2H, H-α), 1.17–1.37 (m, 2H, H-β), 2.49–2.79 (m, 2H, H-γ ),2.64–3.39 (m, 6H, H-4,6,11), 3.76 (s, 3H, PhCH3), 3.70–3.83 (m, 6H, H-3,7,10), 5.18 (br,1H, NH), 6.69 (br, 1H, NH), 7.51–8.50 (m, 4H, Ph-H). ESI-MS: 366 [M+H]+. Calcd.for C17H27N3O4Si: C, 55.86; H, 7.45; N, 11.50; Si, 7.67%. Found: C, 55.67; H, 7.49; N,11.44; Si, 7.59%.

General Procedure for the Preparation of 5a–6b

Triphosgene, 10 mmol, diluted with 10-mL CHCl3 was slowly added to 10-mmol5-fluorouracil dissolved in 5-mL pyridine and the mixture was stirred at –5◦C for 5 ∼ 6 hunder nitrogen for protection. 10 mmol of 1a or 1b and 2-mL triethylamine were addedto the above solution, which reacted at room temperature for 2 ∼ 3 h. The progress of thereaction was monitored by thin-layer chromatography (TLC). Compounds 6a and 6b havebeen described previously.17

N-(5-Fluorouracil-1-yl)formyl-γ -aminopropylsilatrane (5a). 1H NMR:0.25–0.45 (m, 2H, H-α), 1.35–1.65 (m, 2H, H-β), 2.11–2.43 (m, 2H, H-γ ), 2.71–2.79 (m,6H, H-4,6,11), 3.85–4.20 (m, 6H, H-3,7,10), 5.48 (br, 1H,NH), 7.34 (br, 1H, FU-H), 7.92(br, 1H, FU-H). ESI-MS: 389 [M+H]+. Calcd. for C14H21FN4O6Si: C, 43.29; H, 5.45; N,14.42; Si, 7.23%. Found: C, 43.42; H, 5.65; N, 14.03; Si, 7.42%.

N-(5-Fluorouracil-1-yl)formyl-γ -aminopropyl-3,7,10-trimethylsilatrane

(5b). 1H NMR: 0.20–0.42 (m, 2H, H-α), 1.14–1.30 (m, 9H, CH3–3,7,10), 1.43–1.63 (m,2H, H-β), 2.11–2.45 (m, 2H, H-γ ), 2.62–3.28 (m, 6H, H-4,6,11), 3.85–4.20 (m, 3H,H-3,7,10), 5.48 (br, 1H,NH), 7.32 (br, 1H, FU-H), 7.89 (br, 1H, FU-H). ESI-MS: 431[M+H]+. Calcd. for C17H27FN4O6Si: C, 47.43; H, 6.32; N, 13.01; Si, 6.52%. Found: C,47.42; H, 6.45; N, 13.03; Si, 6.42%.

MTT Assay

The MTT assay was performed to evaluate the cytotoxic and anti-proliferative activ-ities of all compounds. The cells were treated with various concentrations (0.4, 2, 10, 50,and 100 μg/mL) of compound in 96-well culture plates for 24 h in final volumes of 100 μL(5 × 103 cells/well). Then 20 μL of MTT solution (5 mg/mL) was added to each well, andthe cells were incubated for an additional 4 h. The medium was carefully removed, and theresidues were dissolved in 150 μL of dimethyl sulfoxide (DMSO), shaken mechanicallyfor 30 min, and absorbance values at a wavelength of 570 nm were collected on an ELX800microplate reader. IC50 values were calculated using percentage of growth versus untreatedcontrol by SPSS.

Dow

nloa

ded

by [

Purd

ue U

nive

rsity

] at

19:

32 3

1 A

ugus

t 201

4

518 G. PING ET AL.

REFERENCES

1. Iwamiyat, J. H.; Maciel, G. E. J. Am. Chem. Soc. 1993, 115, 6835-6842.2. Chernyshev, E. A.; Knyazev, S. P.; Kirin, V. N.; Vasilev, I. M.; Alekseev, N. V. Russ. J. Gen.

Chem. 2004, 74, 58-65.3. Ignatyev, I. S.; Sundius, T. Spectrochim. Acta A. 2012, 95, 37-45.4. Lukevits, E.; Pudova, O. A. Chem. Heterocycl. Comp. 1996, 32, 1605-1646.5. Puri, J. K.; Singh, R.; Chahal, V. K. Chem. Soc. Rev. 2011, 40, 1791-1840.6. Dumitriu, A.-M.-C.; Cazacu, M.; Shova, S.; Turta, C.; Simionescu, B. C. Polyhedron 2012, 33,

119-126.7. Lin Y.; Song, B.; Han, A.; Hu, S.; Ye, F. Q.; Xie, Z. X. Phosphorus Sulfur Silicon Relat. Elem.

2011, 186, 298-303.8. Nasim, M.; Tharmaraj, P.; Venkataramani, P. S. Synth. React. Inorg. Met.-Org. Chem. 1999, 29,

1249-1263.9. Kazimirovskaya, V. B.; D’yakov, V. M.; Voronkov, M. G. Pharmac. Chem. J. 2001, 35, 465-467.

10. Kang, J. D.; Kim, S. J.; Park, S. D. Korean J. Dermatol. 2004, 42, 1138-1144.11. Kim, S. J.; Chai, K. Y.; Park, S. D. Korean J. Dermatol. 2005, 43, 782-787.12. Sculimbrene, B. R.; Decanio, R. E.; Peterson, B. W.; Muntel, E. E.; Fenlon, E. E. Tetrahedron

Lett. 2001, 42, 4979-4982.13. Voronkov, M. G.; Baryshok, V. P. J. Pharmac. Chem. 2004, 38, 3-9.14. Black, C. A.; Ucci, J. W.; Vorpagel, J. S.; Mauck, M. C.; Fenlon, E. E. Bioorg. Med. Chem. Lett.

2002, 12, 3521-3523.15. Kozlowski, H.; Radecki, A.; Łukasiak, J.; Hrabowska, M. Exp. Pathol. 1985, 28, 215-223.16. Hu, L. C.; Ye, F. Q; Guo, P.; Liu, J. M.; Xie, Z. X. Chin. J. Med. Chem. 2007, 17, 295-298.17. Guo, P.; Ye, F. Q.; Liu, J. M.; Hu, L. C. Chin. J. Med. Chem. 2007, 17, 50-51.

Dow

nloa

ded

by [

Purd

ue U

nive

rsity

] at

19:

32 3

1 A

ugus

t 201

4