張麗娜, 姜羽佳, 陳佰靈, 趙志剛

（西南民族大學化學與環(huán)境保護工程學院, 四川 成都 610041）

新型膽酸縮氨基硫脲衍生物的合成與抗菌活性研究

張麗娜, 姜羽佳, 陳佰靈, 趙志剛

（西南民族大學化學與環(huán)境保護工程學院, 四川 成都 610041）

通過甾酮與取代氨基硫脲縮合, 合成了一系列新型的膽酸縮氨基硫脲衍生物. 其結(jié)構(gòu)均經(jīng)1H NMR, IR, ESI-MS及元素分析所證實. 此外, 所有目標化合物都進行了對金黃色葡萄球菌, 枯草芽孢桿菌, 綠膿桿菌, 大腸桿菌的抗菌活性測試. 化合物4b, 4g和4h對綠膿桿菌和大腸桿菌都具有良好的抑制效果.

膽酸; 縮氨基硫脲; 抗菌活性

近年來, 各種各樣的致病細菌對動植物造成了嚴重破壞[1], 并給社會和經(jīng)濟帶來了嚴重性后果. 由于細菌感染, 每年有許多人正遭受著身心的巨大痛苦, 不幸的是, 一些人甚至死于此. 隨著耐藥細菌多樣性的出現(xiàn)[2], 發(fā)展新型且有效的抗菌藥物來降低感染率是迫在眉睫的需求.

在生物活性的研究領(lǐng)域, 作為一類廣譜有機化合物, 縮氨基硫脲類衍生物已受到了越來越多化學家與生物學家的廣泛關(guān)注[3]. 近期的研究結(jié)果表明, 縮氨基硫脲類化合物具有良好的生物活性[4], 包括抗細菌[5-7], 抗真菌[8-9],抗腫瘤[10-11], 抗寄生蟲[12], 抗瘧疾[13-14], 抗病毒[15], 抗艾滋病和抗單純皰疹病[16-17].

目前, 雖然已有許多基于甾體單元修飾的文章, 包括衍生化, 環(huán)化[18], 但關(guān)于膽酸席夫堿卻鮮有報道. 眾所周知, 膽酸在生物系統(tǒng)中豐富且十分重要, 同時其顯示出相對低的毒性以及良好的生物相容性[19]. 根據(jù)活性因子疊加原理, 我們預(yù)期含有膽酸單元和硫脲基團的縮氨基硫脲衍生物具有高效的抗菌活性. 在此, 我們報告新型膽酸縮氨基硫脲衍生物的合成以及這些化合物對四種致病菌株(大腸桿菌、枯草芽孢桿菌、綠膿桿菌、金黃色葡萄)的抗菌活性評估. 其合成路線見Scheme 1.

1 實驗部分

1.1 儀器與試劑

WRS-1B型數(shù)字顯示顯微熔點儀(溫度計未經(jīng)校正); Wzz-2B型自動旋光儀(CH2Cl2為溶劑); Agilent-400MHz型核磁共振儀(TMS作內(nèi)標, CDCl3作溶劑); PERKIN-ELMER1700型紅外光譜儀(KBr壓片); FINNIGAN-LCQ型質(zhì)譜儀; VarioMICRO自動元素分析儀; 三申-YX280A型手提式高壓蒸汽滅菌鍋; 東聯(lián)- DL-CJ-1N型垂直層流潔凈工作臺; 友聯(lián)-HY-2A型數(shù)顯調(diào)速多用振蕩器; 銳品-ECA-9272型電熱恒溫培養(yǎng)箱, 所用試劑均為分析純.

1.2 取代氨基硫脲1a-j的合成

在裝有0.01 mol取代胺溶液、15 mL無水乙醇的三頸瓶中, 加入2 mL濃氨水, 不斷攪拌下緩慢滴加0.8 mL二硫化碳, 并控制此混合溶液在15-20 ℃反應(yīng)1-2 h, 可見反應(yīng)逐漸析出固體. 渾濁體系中加入1.2 g(0.01 mol)氯乙酸鈉, 攪拌后加入1.2 mL 85%的水合肼, 于60 ℃下冷凝回流反應(yīng)4 h, TLC監(jiān)測反應(yīng). 反應(yīng)完全后, 冷卻, 減壓抽濾. 將固體粗產(chǎn)物用乙醇重結(jié)晶, 得到純品取代氨基硫脲1a-j.[20]

1.3 中間體2的合成

在燒瓶中加入0.41 g(1.0 mmol)膽酸, 15 mL無水甲醇, 0.3 mL濃鹽酸, 室溫反應(yīng)4 h, TLC監(jiān)測反應(yīng). 反應(yīng)完全后, 減壓蒸餾除去過量甲醇, 固體用20 mL乙酸乙酯溶解后, 依次用飽和NaHCO3溶液(3×20 mL)洗滌, 飽和食鹽水(3×20 mL)洗滌, 再加無水Na2SO4干燥過夜. 減壓抽濾后, 粗產(chǎn)物經(jīng)柱層析分離純化, 得白色晶體.[21]

1.4 中間體3的合成

0.42g(1.0 mmol) 中間體2溶于20 mL干燥的CH2Cl2, 加入0.69 g(3.2 mmol)PCC, 室溫攪拌9 h, TLC監(jiān)測反應(yīng). 反應(yīng)完全后, 旋干CH2Cl2, 加入20 mL乙酸乙酯溶解, 粗產(chǎn)物經(jīng)柱層析分離純化, 得白色晶體.[21]

1.5 膽酸縮氨基硫脲4a-j的合成通法

0.42g(1.01 mmol)中間體3和1.0 mmol取代氨基硫脲溶于20 mL無水乙醇中, 加入兩滴濃鹽酸, 室溫反應(yīng)4-6 h, 并用TLC監(jiān)測反應(yīng)進程. 反應(yīng)完全后, 減壓抽濾, 固體粗產(chǎn)物用乙醇重結(jié)晶得純品目標物.

4a: 白色固體, 產(chǎn)率90%, m.p. 188-189℃;= -136.12 (c 0.57, CH2Cl2); IR (KBr): 3328, 2973, 2884, 1735, 1705, 1600, 1539, 1476, 1441, 1383, 1348, 1264, 1180, 1101, 1048, 756 cm-1;1H NMR (400 MHz, CDCl3) δ: 9.23 (s, 1H, NH), 8.62 (d, 1H, J = 11.2 Hz, NH), 7.63 (d, 2H, J =7.6 Hz, ArH), 7.38 (m, 2H, ArH), 7.22 (m, 1H, ArH), 3.67 (s, 3H, COOCH3) , 1.37 (s, 3H, 19-CH3), 1.07 (s, 3H, 18-CH3), 0.85 (d, 3H, J = 6.4 Hz, 21-CH3); ESI-MS m/z (%): 588 ([M+23]+, 100). Ana1. Calcd for C32H43N3O4S: C, 67.93; H, 7.66; N, 7.43. Found: C, 67.82; H, 7.64; N, 7.45.

4b: 白色固體, 產(chǎn)率85%, m.p. 211-212℃;= -109.73 (c 0.60, CH2Cl2); IR (KBr): 3298, 2968, 2882, 1741, 1707, 1584, 1532, 1481, 1391, 1269, 1186, 1067, 1006, 821 cm-1;1H NMR (400 MHz, CDCl3) δ∶ 9.19 (s, 1H, NH), 8.64 (d, 1H, J = 6.4 Hz, NH), 7.56 (d, 2H, J = 8.8 Hz, ArH), 7.48 (d, 2H, J = 8.8 Hz, ArH), 3.67 (s, 3H, COOCH3), 1.38(s, 3H, 19-CH3), 1.07 (s, 3H, 18-CH3), 0.85 (d, 3H, J = 6.4 Hz, 21-CH3); ESI-MS m/z (%): 668 ([M+23]+, 100). Ana1. Calcd for C32H42BrN3O4S: C, 59.62; H, 6.57; N, 6.52. Found: C, 59.71; H, 6.59; N, 6.54.

4c: 白色固體, 產(chǎn)率87%, m.p. 148-149℃;= -76.58 (c 0.56, CH2Cl2); IR (KBr): 3315, 2968, 2881, 1736, 1708, 1600, 1539, 1460, 1381, 1236, 1189, 1108, 1029, 747 cm-1;1H NMR (400 MHz, CDCl3) δ∶ 9.75 (s, 1H, NH), 8.67 (t, 1H, J = 6.8 Hz, ArH), 8.57 (d, 1H, J = 11.2 Hz, NH), 7.13 (t, 1H, J = 8.0 Hz, ArH), 6.99 (t, 1H, J = 8.0 Hz , ArH), 6.91 (d, 1H, J = 8.0 Hz, ArH), 3.89 (s, 3H, Ar-OCH3), 3.67(s, 3H, COOCH3), 1.38 (s, 3H, 19-CH3), 1.07 (s, 3H, 18-CH3), 0.85 (d, 3H, J = 6.8 Hz, 21-CH3); ESI-MS m/z (%): 618 ([M+23]+, 100). Ana1. Calcd for C33H45N3O5S: C, 66.53; H, 7.61; N, 7.05. Found: C, 66.62; H, 7.63; N, 7.03.

4d: 白色固體, 產(chǎn)率87%, m.p. 186-187℃;= -85.31 (c 0.60, CH2Cl2); IR (KBr): 3285, 2966, 2884, 1745, 1707, 1598, 1537, 1463, 1380, 1297, 1166, 1044, 781, cm-1;1H NMR (400 MHz, CDCl3) δ∶ 9.24 (s, 1H, NH), 8.59 (d, 1H, J = 10.0 Hz, NH), 7.45 (s, 1H, ArH), 7.26 (t, 1H, J = 8.0 Hz, ArH), 7.12 (d, 1H, J = 8.0 Hz, ArH), 6.77 (d, 1H, J = 8.4 Hz, ArH), 3.82 (s, 3H, Ar-OCH3), 3.67 (s, 3H, COOCH3), 1.38 (s, 3H, , 19-CH3), 1.07 (s, 3H, 18-CH3), 0.85 (d, 3H, J = 6.8 Hz, 21-CH3); ESI-MS m/z (%): 618 ([M+23]+, 100). Ana1. Calcd for C33H45N3O5S: C, 66.53; H, 7.61; N, 7.05. Found: C,66.45; H, 7.59; N, 7.07.

4e: 白色固體, 產(chǎn)率85%, m.p. 197-198℃;= -97.27 (c 0.60, CH2Cl2); IR (KBr): 3316, 2955, 2887, 1747, 1705, 1583, 1530, 1488, 1448, 1382, 1273, 1210, 1174, 1100, 741 cm-1;1H NMR (400 MHz, CDCl3) δ∶ 8.98 (s, 1H, NH), 8.67 (d, 1H, J = 12.0 Hz, NH), 7.64 (t, 1H, J = 6.8 Hz, ArH), 7.25-7.18 (m, 3H, ArH), 3.67 (s, 3H, COOCH3), 2.30 (s, 3H, Ar-CH3), 1.38 (s, 3H, 19-CH3), 1.07 (s, 3H, 18-CH3), 0.85 (d, 3H, J = 6.8 Hz, 21-CH3); ESI-MS m/z (%): 1197 ([2M+39]+, 100). Ana1. Calcd for C33H45N3O4S: C, 68.36; H, 7.82; N, 7.25. Found: C,68.47; H, 7.84; N, 7.23.

4f: 白色固體, 產(chǎn)率90%, m.p. 196-197℃;= -100.56 (c 0.57, CH2Cl2); IR (KBr): 3307, 2967, 2885, 1744, 1707, 1599, 1538, 1483, 1440, 1379, 1276, 1168, 1045, 781 cm-1;1H NMR (400 MHz, CDCl3) δ∶1H NMR (400 MHz, CDCl3) δ∶ 9.28 (s, 1H, NH), 9.63 (d, 1H, J = 8.0 Hz, NH), 7.66 (d, 1H, J = 10.4 Hz, ArH), 7.37-7.29 (m, 2H, ArH), 6.91 (t, 1H, J = 7.6 Hz, ArH), 3.67 (s, 3H, COOCH3), 1.38 (d, 3H, 19-CH3), 1.07 (s, 3H, 18-CH3), 0.84 (d, 3H, J = 6.8 Hz, 21-CH3); ESI-MS m/z (%): 606 ([M+23]+, 100). Ana1. Calcd for C32H42FN3O4S: C, 65.84; H, 7.25; N, 7.20. Found: C,65.95; H, 7.22; N, 7.18.

4g: 白色固體, 產(chǎn)率88%, m.p. 191-192℃;=110.92 (c 0.55, CH2Cl2); IR (KBr): 3318, 2974, 2879, 1735, 1705, 1597, 1535, 1473, 1439, 1383, 1345, 1265, 1180, 834 cm-1;1H NMR (400 MHz, CDCl3) δ∶ 9.13 (s, 1H, NH), 8.66 (d, 1H, J = 7.6 Hz, NH), 7.57-7.53 (m, 2H, ArH), 7.07 (t, 2H, J = 8.4 Hz, ArH), 3.67 (s, 3H, COOCH3), 1.38 (s, 3H, 19-CH3), 1.07 (s, 3H, 18-CH3), 0.81 (d, 3H, J = 6.8 Hz, 21-CH3); ESI-MS m/z (%): 606 ([M+23]+, 100). Ana1. Calcd for C32H42FN3O4S: C, 65.84; H, 7.25; N, 7.20. Found: C,65.75; H, 7.27; N, 7.22.

4h: 白色固體, 產(chǎn)率86%, m.p. 168-169℃;= -52.84 (c 0.56, CH2Cl2); IR (KBr): 3307, 2950, 2886, 1736, 1707, 1586, 1529, 1486, 1437, 1375, 1267, 1186, 1101, 752 cm-1;1H NMR (400 MHz, CDCl3) δ∶ 9.71 (s, 1H, NH), 8.69 (d, 1H, J = 12.0 Hz, NH), 8.57 (t, 1H, J=7.2 Hz, ArH), 7.42 (d, 1H, J = 8.0 Hz, ArH), 7.31 (t, 1H, J = 7.2 Hz , ArH), 7.14 (t, 1H, J = 7.6 Hz, ArH), 3.67 (s, 3H, COOCH3), 1.37 (d, 3H, 19-CH3), 1.07 (s, 3H, 18-CH3), 0.84 (d, 3H, J = 6.8 Hz, 21-CH3); ESI-MS m/z (%): 622 ([M+23]+, 100). Ana1. Calcd for C32H42ClN3O4S: C, 64.03; H, 7.05; N, 7.00. Found: C,64.15; H, 7.07; N, 6.98.

4i: 白色固體, 產(chǎn)率88%, m.p. 206-207℃;= -65.15 (c 0.57, CH2Cl2); IR (KBr): 3301, 2967, 2883, 1741, 1706, 1586, 1531, 1483, 1381, 1269, 1186, 1092, 826 cm-1;1H NMR (400 MHz, CDCl3) δ∶ 9.20 (s, 1H, NH), 8.66 (d, 1H, J = 6.4 Hz, NH), 7.60 (d, 2H, J = 8.8 Hz, ArH), 7.34 (d, 2H, J = 8.4 Hz, ArH), 3.67 (s, 3H, COOCH3), 1.37 (s, 3H, J=4.8 Hz, 19-CH3), 1.07 (s, 3H, 18-CH3), 0.84 (d, 3H, J = 6.4 Hz, 21-CH3); ESI-MS m/z (%): 622 ([M+23]+, 100). Ana1. Calcd for C32H42ClN3O4S: C, 64.03; H, 7.05; N, 7.00. Found: C,64.17; H, 7.03; N, 7.02.

4j: 白色固體, 產(chǎn)率82%, m.p. 182-183℃;= -80.72 (c 0.56, CH2Cl2); IR (KBr): 3305, 2965, 2884, 1746, 1706, 1594, 1533, 1479, 1379, 1243, 1182, 823 cm-1;1H NMR (400 MHz, CDCl3) δ∶ 9.06 (s, 1H, NH), 8.62 (d, 1H, J = 14.4 Hz, NH), 7.45 (d, 2H, J = 8.8 Hz, ArH), 6.91 (d, 2H, J = 8.8 Hz, ArH), 3.82 (s, 3H, Ar-OCH3), 3.67 (s, 3H, COOCH3), 1.38 (s, 3H, 19-CH3), 1.07 (s, 3H, 18-CH3), 0.84 (d, 3H, J = 6.4 Hz, 21-CH3); ESI-MS m/z (%): 618 ([M+23]+, 100). Ana1. Calcd for C33H45N3O5S: C, 66.53; H, 7.61; N, 7.05. Found: C,66.40; H, 7.64; N, 7.03.

2 結(jié)果與討論

2.1 光譜分析

化合物4a-j的其結(jié)構(gòu)均經(jīng)1H NMR, IR, ESI-MS及元素分析所確認. 質(zhì)譜均顯示出預(yù)期的高強度分子峰. 紅外光譜中, 3328-3285 cm-1的強吸收峰為N-H伸縮震動的特征峰, 1600-1583 cm-1與1297-1236 cm-1范圍內(nèi)的強吸收峰分別歸屬于C=N與C=S基團. 1707-1705 cm-1范圍內(nèi)的強吸收峰為甾酮中C=O基團的特征峰, 1747-1735 cm-1則為COOCH3中C=O的吸收峰. 核磁氫譜中, δ 8.98-9.75 ppm間的單峰為NH的質(zhì)子峰, δ 8.56-8.71 ppm間的雙峰則為另一個NH的質(zhì)子峰. 此外, 位于δ 1.37-1.38 ppm和δ 1.07 ppm的單峰與δ 0.84-0.86 ppm的雙峰為甾體上甲基質(zhì)子的特征峰, δ 3.67 ppm處的單峰為COOCH3的質(zhì)子峰.

2.2 體外抗菌活性測試

化合物4a-j的體外抗菌活性測試使用兩種革蘭氏陽性細菌(金黃色葡萄球菌、枯草芽孢桿菌)和兩種革蘭氏陰性細菌(綠膿桿菌、大腸桿菌), 阿莫西林(25 μg)與環(huán)丙沙星(25 μg)作為標準對照藥物. 采用二倍稀釋法來計算試管中含菌體數(shù)為105CFU mL?1的標準培養(yǎng)液的MIC. 測試前, 先將化合物溶解于1 mL DMSO中, 依次稀釋至最終濃度分別為256, 128, 64, 32, 16, 8, 4, 2, 1, 0.5, 0.25 μg mL?1, 每支試管中加入1 mL 0.5馬克法蘭氏濁度標準的菌液. MIC直觀地決定于在37 ℃孵化16 h后明顯增長的抑制. 此外, IC50值則由含菌體數(shù)為105CFU mL?1的標準培養(yǎng)液的抑菌圈測試來計算. 測試前, 先將待測物溶解于2 mL DMSO中, 依次稀釋至最終濃度分別為640, 320, 160, 80, 40, 20, 10, 5 μg mL?1, 0.5馬克法蘭氏濁度標準的菌液在肉汁培養(yǎng)基中培養(yǎng)后, 用待測物稀釋位于表面增長的細菌使濾紙(直徑6 mm)飽和. 37 ℃孵化16 h后得到抑菌圈直徑, 由此計算出IC50值. MIC與IC50值見表1.

表1 膽酸縮氨基硫脲衍生物4a-j與兩種陽性對照(環(huán)丙沙星與阿莫西林)的抗菌活性Table 1 Antibacterial activity of cholic acid thiosemicarbazone derivatives 4a-j and two positive controls (Ciprofloxacin and Amoxicillin)

-, 無抑菌活性

如表1所示, 化合物4b, 4g和4h對綠膿桿菌與大腸桿菌顯示出良好的抗菌活性, 其中4g對大腸桿菌的抗菌活性與阿莫西林相當, 無化合物對金黃色葡萄球菌與枯草芽孢桿菌有抗菌活性. 初步實驗結(jié)果表明, 苯環(huán)上不同的取代基團, 對化合物的生物活性有不同影響. 苯環(huán)上有吸電子基團如氟、溴的化合物顯示出良好的抗菌活性,然而引入給電子基團如甲基或甲氧基則會對其活性產(chǎn)生不利影響. 進一步的抗菌活性還在研究中.

[1] HERNANDES M Z, RABELLO M M, LEITE A C L, et al. Studies toward the structural optimization of novel thiazolylhydrazonebased potent antitrypanosomal agents[J]. Bioorg Med Chem, 2010, 18: 7826-7835.

[2] PARRILHA G L, SILVA J G D, GOUVEIA L F, et al. Pyridine-derived thiosemicarbazones and their tin(IV) complexes with antifungal activity against Candida spp[J]. Eur J Med Chem, 2011, 46: 1473-1482.

[3] PAVAN F R, MAIA P I S, LEITE S R A, et al. Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones:Anti-mycobacterium tuberculosis activity and cytotoxicity [J]. Eur J Med Chem, 2010, 45: 1898-1905.

[4] KANG I J, WANG L W, HSU T A, et al. Isatin-β-thiosemicarbazones as potent herpes simplex virus inhibitors [J]. Bioorg Med Chem Lett, 2011, 21: 1948-1952.

[5] KHAN S A, KUMAR P, JOSHI R, et al. Synthesis and in vitro antibacterial activity of new steroidal thiosemicarbazone derivatives [J]. Eur J Med Chem, 2008, 43: 2029-2034.

[6] ZHU Y J, SONG K K, LI Z C, et al. Antityrosinase and antimicrobial activities of trans-cinnamaldehyde thiosemicarbazone [J]. J Agric Food Chem, 2009, 57: 5518-5523.

[7] KHANDANI M, SEDAGHAT T, ERFANI N, et al. Synthesis, spectroscopic characterization, structural studies and antibacterial and antitumor activities of diorganotin complexes with 3-methoxysalicylaldehyde thiosemicarbazone [J]. J Mol Struct, 2013, 1037: 136-143.

[8] OPLETALOVA V, KALINOWSKI D S, VEJSOVA M, et al. Identification and characterization of thiosemicarbazones with antifungal and antitumor effects: cellulariron chelation mediating cytotoxic activity [J]. Chem Res Toxicol, 2008, 21: 1878-1889.

[9] ALOMAR K, LANDREAU A, ALLAIN M, et al. Synthesis, structure and antifungal activity of thiophene-2,3-dicarboxaldehyde bis(thiosemicarbazone) and nickel(II), copper(II) and cadmium(II) complexes: Unsymmetrical coordination mode of nickel complex [J]. J Inorg Biochem, 2013, 126: 76-83.

[10] JANSSON P J, SHARPE P C, BERNHARDT P V, et al. Novel thiosemicarbazones of the ApT and DpT Series and their copper complexes: identification of pronounced redox activity and characterization of their antitumor activity [J]. J Med Chem, 2010, 53: 5759-5769.

[11] ALI A A, NIMIR H, AKTAS C, et al. Organoplatinum(II) complexes with 2-acetylthiophene thiosemicarbazone: synthesis, characterization, crystal structures, and in vitro antitumor activity [J]. Organometallics, 2012, 31: 2256-2262.

[12] CHELLAN P, LAND K M, SHOKAR A, et al. Exploring the versatility of cycloplatinated thiosemicarbazones as antitumor andantiparasitic agents [J]. Organometallics, 2012, 31: 5791-5799.

[13] CHELLAN P, NASSER S, VIVAS L, et al. Cyclopalladated complexes containing tridentate thiosemicarbazone ligands of biological significance: Synthesis, structure and antimalarial activity [J]. J Organomet Chem, 2010, 695: 2225-2232.

[14] KHANYE S D, WAN B, FRANZBLAU S G, et al. Synthesis and in vitro antimalarial and antitubercular activity of gold(III) complexes containing thiosemicarbazone ligands [J]. J Organomet Chem, 2011, 696: 3392-3396.

[15] KESEL A J, Broad-spectrum antiviral activity including human immunodeficiency and hepatitis C viruses mediated by a novel retinoid thiosemicarbazone derivative [J]. Eur J Med Chem, 2011, 46: 1656-1664.

[16] BAL T R, ANAND B, YOGEESWARI P, et al. Synthesis and evaluation of anti-HIV activity of isatin β-thiosemicarbazone derivatives [J]. Bioorg Med Chem Lett, 2005, 15: 4451-4455.

[17] ALTUN A, KUMRU M, DIMOGLO A. Study of electronic and structural features of thiosemicarbazone and thiosemicarbazide derivatives demonstrating anti-HSV-1 activity[J]. J Mole Struct (Theochem), 2001, 535: 235-246.

[18] CHHIKARA B S, CHANDRA R, TANDON V. IBX in an ionic liquid: eco-friendly oxidation of 17α-methylandrostan-3β,17β-diol, an intermediate in the synthesis of anabolic oxandrolone [J]. Tetrahedron Lett, 2004, 45: 7585-7588.

[19] DUTTA S, KAR T, MANDAL D, et al. Structure and Properties of Cholesterol-based Hydrogelators with Varying Hydrophilic Terminals: Biocompatibility and Development of Antibacterial Soft Nanocomposites[J]. Langmuir, 2013, 29: 316-327.

[20] ZHAO Z G, LIU X L, LIU L L, et al. Microwave-assisted synthesis of new steroidal thiosemicarbazones derived from methyl 3-oxocholanate under solvent-free conditions [J]. J Chem Res, 2010, 34: 455-458.

[21] 崔建國, 黃立粱, 黃燕敏, 等. 一種具有抗腫瘤活性膽酸衍生物的合成新方法[J]. 有機化學, 2009, 29: 971-974.

Synthesis and evaluation of antimicrobial activities of novel cholic acid thiosemicarbazone derivatives

ZHANG Li-na, JIANG Yu-jia, CHEN Bai-ling, ZHAO Zhi-gang
( College of Chemistry and Environmental Protection Engineering, Southwest University for Nationalities, Chengdu 610041, P. R. C. )

A series of novel cholic acid thiosemicarbazone derivatives via the condensation of steroidal ketones and substituted thiosemicarbazides were synthesized. Their structures were elucidated by1H NMR, IR, ESI-MS spectra and elemental analyses. Moreover, all target compounds were tested for antibacterial activity againstStaphylococcus aureus, Bacillus subtilis, Pseudomanas aeroginosa and Escherichia coli.Compounds 4b, 4g and 4h possess good inhibitory effects againstP. aeruginosaandE. Coli.

cholic acid; thiosemicarbazone; antimicrobial activity

O621.3,R914.5

A

1003-4271(2014)02-0219-05

10.3969/j.issn.1003-4271.2014.02.09

2014-01-17

趙志剛(1963-), 男, 教授, 博士, 碩士生導師, 研究方向: 生物有機化學, 超分子化學與分子自組裝, 藥物合成, 微波化學等方面的研究. E-mail: zzg63129@163.com

四川省應(yīng)用基礎(chǔ)研究項目(No.2011JY0035); 四川省科技支撐計劃項目(No. 2012SZ0160); 西南民族大學2014年研究生創(chuàng)新型科研項目(CX2014SZ43)