127-33-3

• 常用中文名：地美环素
• 常用英文名：Demeclocycline
• CAS号：127-33-3
• 分子式：C₂₁H₂₁ClN₂O₈
• 分子量：464.853
• 相关类别： 信号通路 抗感染 细菌
• 发布时间：2018-08-10 09:05:33
• 更新时间：2024-01-05 17:41:57
• 去甲环素是一种口服活性四环素抗生素。去甲环素通过与30S核糖体亚基结合来抑制氨基酰基tRNA的结合,从而损害蛋白质合成。脱氯环素对多种细菌感染具有抗菌活性[1][2]。

名称

• 中文名: 地美环素
• 英文名: demeclocycline
• 英文别名: Ledermycin hydrochloride; 7-chloro-6-demethyltetracycline; 6-demethyl-7-chlorotetracycline; (2E,4S,4aS,5aS,6S,12aS)-2-[Amino(hydroxy)methylene]-7-chloro-4-(dimethylamino)-6,10,11,12a-tetrahydroxy-4a,5a,6,12a-tetrahydrotetracene-1,3,12(2H,4H,5H)-trione; Elkamicina; DMCTC; (4aS)-7-Chlor-4c-dimethylamino-3,6t,10,12,12a-pentahydroxy-1,11-dioxo-(4ar,5ac,12ac)-1,4,4a,5,5a,6,11,12a-octahydro-naphthacen-2-carbonsaeure-amid; Declomycin; EINECS 204-834-8; Demeclocyclinum; 7-chloro-4-dimethylamino-3,6,10,12,12a-pentahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-naphthacene-2-carboxylic acid amide; (2E,4S,4aS,5aS,6S,12aS)-2-[Amino(hydroxy)methylene]-7-chloro-4-(dimethylamino)-6,10,11,12a-tetrahydroxy-4a,5a,6,12a-tetrahydro-1,3,12(2H,4H,5H)-tetracenetrione; 1,3,12(2H,4H,5H)-Naphthacenetrione, 2-(aminohydroxymethylene)-7-chloro-4-(dimethylamino)-4a,5a,6,12a-tetrahydro-6,10,11,12a-tetrahydroxy-, (2E,4S,4aS,5aS,6S,12aS)-; Demethylchlortetracycline(DMCT); Demeclociclina; Ledermycin; domeclocycline; (4S,4aS,5aS,6S,12aR)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide

物化性质

• 密度: 1.8±0.1 g/cm3
• 沸点: 684.5±55.0 °C at 760 mmHg
• 分子式: C₂₁H₂₁ClN₂O₈
• 分子量: 464.853
• 闪点: 367.8±31.5 °C
• 精确质量: 464.098633
• PSA: 181.62000
• LogP: 0.57
• 蒸汽压: 0.0±2.2 mmHg at 25°C
• 折射率: 1.761
• 储存条件: 室温
• 分子结构:

  1、 摩尔折射率：109.25

  2、 摩尔体积（cm³/mol）：265.1

  3、等张比容（90.2K）：854.8

  4、表面张力（dyne/cm）：107.9

  5、极化率（10^-24cm³）：43.31

• 计算化学:

  1.疏水参数计算参考值（XlogP）:0.7

  2.氢键供体数量:6

  3.氢键受体数量:9

  4.可旋转化学键数量:2

  5.互变异构体数量:132

  6.拓扑分子极性表面积182

  7.重原子数量:32

  8.表面电荷:0

  9.复杂度:961

  10.同位素原子数量:0

  11.确定原子立构中心数量:5

  12.不确定原子立构中心数量:0

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:1

生物活性

• 描述: 去甲环素是一种口服活性四环素抗生素。去甲环素通过与30S核糖体亚基结合来抑制氨基酰基tRNA的结合,从而损害蛋白质合成。脱氯环素对多种细菌感染具有抗菌活性[1][2]。
• 相关类别:
  研究领域 >> 癌症
  研究领域 >> 感染
  研究领域 >> 炎症/免疫
  信号通路 >> 抗感染 >> 细菌
• 体外研究: 脱氯环素(0-100μM；24小时)处理降低mpkCCD细胞中AQP2的丰度[3]。去甲环素(10μM；24小时)治疗促进单核细胞和巨噬细胞的活性[4]。去甲环素(1-10μM；72小时)治疗直接影响脑肿瘤细胞的生长[4]。Western印迹分析[3]细胞系：MpkCCD细胞浓度：0-100μM孵育时间：24小时结果：MpkCCD细胞中AQP2丰度降低,在50μM时有显著影响。细胞存活率测定[4]细胞系：小鼠骨髓来源的巨噬细胞和单核细胞浓度：10μM孵育时间：24小时结果：增强TNF-α的产生并调节单核细胞功能。细胞存活率测定[4]细胞系：脑肿瘤起始细胞浓度：1、5和10μM孵育时间：72小时结果：通过两种方式抑制细胞生长：使用单核细胞作为中介,并直接影响脑肿瘤起始的细胞增殖和球体形成能力。
• 体内研究: 去甲环素(腹腔注射；40mg/kg；每日一次；48小时)治疗可显著降低低钠血症,显著纠正低渗透压,且无肾毒性[3]。动物模型：低钠血症雄性Wistar大鼠[3]剂量：40mg/kg给药：腹腔注射；40mg/kg；每日一次；48小时结果：尿量增加,尿渗透压降低,并导致水排泄分数显著增加。动物模型：低钠血症雄性Wistar大鼠[3]剂量：40mg/kg给药：腹腔注射；40mg/kg；每日一次；48小时结果：表明肾内髓质对AQP2和AC5/6有特异性作用,而非二次毒性作用。
• 参考文献:

  [1]. I Chopra, et al. Tetracyclines, molecular and clinical aspects. J Antimicrob Chemother. 1992 Mar;29(3):245-77.

  [2]. D Schnappinger, et al. Tetracyclines: antibiotic action, uptake, and resistance mechanisms. Arch Microbiol. 1996 Jun;165(6):359-69.

  [3]. Marleen L A Kortenoeven, et al. Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla. Am J Physiol Renal Physiol. 2013 Dec 15;305(12):F1705-18.

  [4]. Susobhan Sarkar, et al. Demeclocycline Reduces the Growth of Human Brain Tumor-Initiating Cells: Direct Activity and Through Monocytes. Front Immunol. 2020 Feb 21;11:272.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : QI7650000 CHEMICAL NAME : 2-Naphthacenecarboxamide, 7-chloro-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octah ydro- 3,6,10,12,12a-pentahydroxy-1,11-dioxo- CAS REGISTRY NUMBER : 127-33-3 LAST UPDATED : 199706 DATA ITEMS CITED : 15 MOLECULAR FORMULA : C21-H21-Cl-N2-O8 MOLECULAR WEIGHT : 464.89 WISWESSER LINE NOTATION : L E6 C666 BV FV CU GUTTT&J DQ EQ GVZ HQ IN1&1 MQ OG RQ HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 420 mg/kg/6W TOXIC EFFECTS : Endocrine - diabetes insipidus (nephrogenic or CNS) Biochemical - Metabolism (Intermediary) - effect on cyclic nucleotides TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 10 mg/kg TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 68 mg/kg/8D TOXIC EFFECTS : Kidney, Ureter, Bladder - urine volume increased Kidney, Ureter, Bladder - other changes in urine composition TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >6750 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 358 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 4 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 454 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 2500 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 79 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported DOSE : 240 mg/kg SEX/DURATION : female 1-39 week(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - other postnatal measures or effects TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 5 gm/kg SEX/DURATION : female 1-22 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - skin and skin appendages Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 5 gm/kg SEX/DURATION : female 1-22 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Newborn - other postnatal measures or effects MUTATION DATA TYPE OF TEST : DNA inhibition TEST SYSTEM : Human Lymphocyte DOSE/DURATION : 3750 ug/L REFERENCE : BCPHBM British Journal of Clinical Pharmacology. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1974- Volume(issue)/page/year: 16,127,1983 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5539 No. of Facilities: 10 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 330 (estimated) No. of Female Employees: 120 (estimated)

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