A series of picolyl amides of betulinic acid (3a–3c and 6a–6c) was prepared and subjected to the cytotoxicity screening tests. Structure-activity relationships studies resulted in finding differences in biological activity in dependence on o-, m- and p-substitution of the pyridine ring in the target amides, when cytotoxicity data of 3a–3c and 6a–6c were obtained and compared. The amides 3b and 3a displayed cytotoxicity (given in the IC₅₀ values) in G-361 (0.5 ± 0.1 μM and 2.4 ± 0.0 μM, respectively), MCF7 (1.4 ± 0.1 μM and 2.2 ± 0.2 μM, respectively), HeLa (2.4 ± 0.4 μM and 2.3 ± 0.5 μM, respectively) and CEM (6.5 ± 1.5 μM and 6.9 ± 0.4 μM, respectively) tumor cell lines, and showed weak effect in the normal human fibroblasts (BJ). Selectivity against all tested cancer cells was determined and compared to normal cells with therapeutic index (TI) between 7 and 100 for compounds 3a and 3b. The therapeutic index (TI = 100) was calculated for human malignant melanoma cell line (G-361) versus normal human fibroblasts (BJ). The cytotoxicity of other target amides (3c and 6a–6c) revealed lower effects than 3a and 3b in the tested cancer cell lines.

制备了一系列桦木酸的甲基吡啶甲酰胺（3a - 3c和6a - 6c），并进行了细胞毒性筛选测试。当获得并比较了3a - 3c和6a - 6c的细胞毒性数据时，结构-活性关系研究导致发现了依赖于目标酰胺中吡啶环的o-，m-和p-取代的生物活性差异。酰胺3b和3a表现出细胞毒性（在IC _{50中给出）}值）分别在G-361（分别为0.5±0.1μM和2.4±0.0μM），MCF7（分别为1.4±0.1μM和2.2±0.2μM），HeLa（分别为2.4±0.4μM和2.3±0.5μM）和CEM（分别为6.5±1.5μM和6.9±0.4μM）肿瘤细胞系，在正常人成纤维细胞（BJ）中显示出较弱的作用。确定针对所有测试癌细胞的选择性，并将其与化合物3a和3b的治疗指数（TI）在7至100之间的正常细胞进行比较。计算人恶性黑色素瘤细胞系（G-361）与正常人成纤维细胞（BJ）的治疗指数（TI = 100 ）。其他目标酰胺（3c和6a – 6c）的细胞毒性显示其作用低于3a和3b在测试的癌细胞系中。