4-烷硫基-4-脱氧-4′-去甲表鬼臼毒素的合成和抗肿瘤活性

对4’-去甲表鬼臼毒素的C₄位进行化学修饰,合成和筛选了10个4-烷硫基-4-脱氧-4’-去甲表鬼臼毒素衍生物以进一步研究C₄位不同的原子和取代基与活性之间的关系及寻找结构简单、活性更强的抗肿瘤新药。4’-去甲表鬼臼毒素与硫醇在三氟化硼·乙醚或三氟乙酸存在下生成相应的硫醚,也可用硫醇与4β-溴-4-脱氧-4’-去甲表鬼臼毒素反应生成相应的硫醚。在体外筛选中,化合物10和12抑制L1210白血病细胞的活性与依托泊甙相当或更强,化合物9,10,12和15抑制KB细胞的活性与依托泊甙相当或更强。     

取代苄基/萘甲基异喹啉类及有关季铵衍生物的合成与生物活性

以具心血管活性的异喹啉类生物碱为先导物,结合某些钾通道阻滞剂的结构特征,设计合成了28个3,4-二氢(I_1～4)和1,2,3,4-四氢苄基/萘甲基异喹啉化合物(II_1～18)及有关季铵衍生物(I_5,6和II_19～22)。药理试验表明:除化合物I₄有一定升压作用外,大多化合物有不同程度的降压和减慢心率活性,其中化合物II1的降压活性最强。分析定量构效关系发现:化合物母核氮原子电荷愈大(即其绝对值愈小),降压作用愈强;反之,减慢心率作用愈强。异喹啉母核氮原子电荷可能为影响作用于血管或心脏组织的重要因素之一。     

用二维核磁共振技术研究野菊花三醇的结构

从野菊花(Chrysanthemum indicum L.)亲脂性极性较大的部分,分离得到一个新的倍半萜成分,命名为野菊花三醇。通过¹H-¹H COSY,¹H-¹³C COSY及远程¹H-¹³C COSY二维核磁共振谱研究,确定其属于(牛龙)牛儿烷衍生物,并确定其结构和相对立体构型。     

四氢异喹啉类化合物的合成和抗血小板聚集活性

某些异喹啉化合物有抗血小板聚集活性,如喘速宁的纯光学异构体R-(+)体有较明显的抗血小板聚集作用。本文重点对四氢异喹啉母核(I₁～I₄)的2位进行取代基修饰,共合成了14个化合物。体外药理筛选结果初步表明,大部分化合物有一定的抗血小板聚集活性,其中II₃,II₅,II₇,II₈和II₁₀活性较强。     

Polymorphisms of the human platelet alloantigens HPA-1, HPA-2, HPA-3, and HPA-4 in ischemic stroke

Polymorphism in human platelet antigen (HPA)-1 and HPA-3 (GPIIb/IIIa), HPA-2 (GPIb/IX), HPA-4 (GPIIIa), and HPA-5 (GPIa/IIa) was investigated in 329 stroke patients and 444 matched control subjects. HPA genotyping was done by PCR-SSP method. Lower HPA-1a (P < 0.001) and higher HPA-1b (P < 0.001) allele frequencies were seen in patients than control subjects, and homozygosity for HPA-1b (P < 0.001) alleles was more prevalent in stroke cases than in controls. The allele and genotype distributions of the other HPA polymorphic variants were similar between cases and controls. Select HPA combined genotypes comprising the 2121 (Pc = 0.008) and 2221 (Pc = 0.018) genotypes, which were positively associated, and the 1111 (Pc < 0.001), which was negatively associated with stroke, thereby conferred a disease susceptibility and protective nature to these genotype combinations. Multivariate analysis confirmed the negative association of the 1111 (P < 0.001) and the positive association of the 2121 (P = 0.017) combined genotypes with stroke, after adjustment for a number of covariates. This is the first evidence demonstrating differential association of the common 4 HPA gene variants and specific HPA genotype combinations with stroke.     

Impact of pharmacy outreach services on blood pressure management in the elderly community of Hong Kong

Aim: To investigate the impact of the Pharmacy Outreach Service (POS) on blood pressure (BP) and disease knowledge among community‐dwelling elderly patients with hypertension, and to evaluate the sustainability of such impact of POS. Methods: A prospective open‐labeled study of elderly adults (aged ≥65 years) with hypertension (BP ≥140/90 mmHg for non‐diabetics and ≥130/80 mmHg for diabetics) was carried out at seven elderly community centers from July 2008 to March 2010. Pharmacists provided BP monitoring, medication review and disease knowledge assessment. The target BP was <140/90 mmHg for non‐diabetics and <130/80 mmHg for diabetics. The primary outcome was BP change, whereas the secondary outcome was the change of disease knowledge of hypertension. All outcomes were compared between baseline and the last visit. For POS 2008/09 participants, BP was compared between values obtained during POS 2008/09 and 2009/10. Results: A total of 97 participants were recruited. Systolic BP reduced significantly from 152.38 ± 18.80 mmHg to 147.04 ± 20.72 mmHg (P = 0.021), and diastolic BP reduced from 73.84 ± 11.36 mmHg to 71.03 ± 10.97 mmHg (P = 0.010). Cumulative reductions in mean systolic BP and diastolic BP throughout the 2‐year study period were 21.39 ± 24.72 mmHg and 9.88 ± 13.48 mmHg, respectively (P < 0.001). A 12% increase in the at‐goal rate was observed in new participants recruited in 2009 (P = 0.039). Disease knowledge of hypertension improved significantly (P < 0.005), particularly in areas that included the definition of hypertension, diet and lifestyle modification. Conclusions: The POS might improve blood pressure control, hypertension and diabetes knowledge in elderly adults with hypertension in Hong Kong. The effect on blood pressure improvement was sustainable. Geriatr Gerontol Int 2013; 13: 175–181.     

柴胡皂甙m和柴胡皂甙n的结构鉴定

从黑柴胡(Bupleurum smithii Wolff)根中分得二个新三萜皂甙。根据理化性质和波谱数据,分别鉴定为3β,23,28-三羟基齐墩果烷-11,13(18)-二烯-3-O-β-D-吡喃葡萄糖基-(1→3)-β-D-吡喃呋糖甙,命名为柴胡皂甙m(saikosaponin m,IV),和3β,16β,23,28-四羟基齐墩果烷-11,13(18)-二烯-3-O-β-D-吡喃葡萄糖基-(1→6)-[α-L-吡喃鼠李糖基-(1→4)]-β-D-吡喃葡萄糖甙,命名为柴胡皂甙n(saikos-aponinn,IX)。