本文選題：查爾酮 + 氨基二硫代甲酸酯　； 參考：《鄭州大學(xué)》2017年碩士論文

【摘要】：氨基二硫代甲酸酯類化合物是一種天然小分子,能夠有效地螯合重金屬以及作為一種單功能性誘導(dǎo)物選擇性增強(qiáng)二相酶活性,因此在臨床藥物研究中得到廣泛應(yīng)用。查爾酮化合物具有1,3-二苯基-丙烯酮結(jié)構(gòu),能夠和不同的藥物作用靶點(diǎn)結(jié)合從而發(fā)揮其藥物活性。因而,對(duì)于這二類天然小分子的研究得到的藥物學(xué)領(lǐng)域廣泛的關(guān)注和研究。本論文根據(jù)文獻(xiàn)報(bào)道,在充分研究具有氨基二硫代甲酸酯類、查爾酮結(jié)構(gòu)化合物構(gòu)效關(guān)系和藥物活性的基礎(chǔ)之上,保留了查爾酮活性片段的完整性,利用克萊森縮合反應(yīng)和拼合原理分別將生物活性基團(tuán)鹵代烷基酰胺類、氨基二硫代甲酸酯、三氮唑等活性片段連分別連接到查爾酮的分子中,共合成的43個(gè)目標(biāo)化合物。具體研究工作如下:第一部分是雜環(huán)類查爾酮衍生物的合成。主要通過克萊森縮合反應(yīng)合成氨基查爾酮和疊氮查爾酮化合物。利用已合成的關(guān)鍵中間體,根據(jù)藥物拼合原理,設(shè)計(jì)并合成了三個(gè)系列共43個(gè)新型查爾酮類衍生物,并且所有合成的化合物均經(jīng)過核磁和質(zhì)譜結(jié)構(gòu)表征。第二部分是生物活性評(píng)價(jià)。對(duì)所合成的43個(gè)新型查爾酮衍生物,采用MTT法進(jìn)行了抗腫瘤相關(guān)活性評(píng)價(jià)。主要選擇性的是人前列腺細(xì)胞(PC-3)、胃癌細(xì)胞(MGC-803)、人食管癌細(xì)胞(EC-109)這三種癌細(xì)胞株。實(shí)驗(yàn)結(jié)果表明大部分鹵代烷基酰胺類化合物和氨基二硫代甲酸酯并查爾酮類衍生物具有較好抗腫瘤活性,其中化合物Ⅰ-1、Ⅰ-2、Ⅰ-4、Ⅱ-4、Ⅱ-7、Ⅱ-10、Ⅱ-15表現(xiàn)出較好的抗腫瘤活性。其中活性最好的是Ⅱ-4。當(dāng)引入鹵代烷基酰胺類和氨基二硫代甲酸酯活性分子,發(fā)現(xiàn)其藥物活性能夠得到有效增加。但是,在此基礎(chǔ)上引入三氮唑結(jié)構(gòu)時(shí),活性卻降低。本論文的工作對(duì)于發(fā)現(xiàn)抗腫瘤活性更好,生物利用度更高的先導(dǎo)小分子提供一定基礎(chǔ)。
[Abstract]:Aminodithiocarbamate is a kind of natural small molecule which can effectively chelate heavy metals and selectively enhance the activity of biphasic enzyme as a mono-functional inducer so it has been widely used in clinical drug research. Chalcone has the structure of 1: 3-diphenyl-propenone and can combine with different drug targets to exert its drug activity. Therefore, the study of these two kinds of natural small molecules has received extensive attention and research in the field of pharmacology. In this paper, based on the full study of the structure-activity relationship and drug activity of amino dithiocarbamate and chalcone, the integrity of the active fragment of chalcone was preserved. By using the Clayson condensation reaction and the splicing principle, the active fragments of bioactive groups, such as haloalkyl amides, amino dithiocarbamate and triazoles, were connected to the molecules of chalcone, respectively, and 43 target compounds were synthesized. The main work is as follows: the first part is the synthesis of heterocyclic chalcone derivatives. Aminocalcone and azacarone compounds were synthesized by Clayson condensation reaction. Three series of 43 new chalcone derivatives were designed and synthesized according to the principle of drug splicing using the key intermediates. All the synthesized compounds were characterized by NMR and MS. The second part is bioactivity evaluation. The anti-tumor activity of 43 new chalcone derivatives was evaluated by MTT method. Three kinds of cancer cell lines were mainly selected: human prostate cell line (PC-3H), gastric cancer cell line (MGC-803) and human esophageal carcinoma cell line (EC-109). The results showed that most of the halogenated amides and derivatives of aminodithiocarbamate and chalcone had good antitumor activity, and compounds 鈪，

本文編號(hào)：1774508