Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
Faculty of Pharmacy, Medical University of Gdańsk, Hallera 107, 80-416 Gdańsk, Poland.
Bioorg Med Chem. 2019 Oct 15;27(20):114923. doi: 10.1016/j.bmc.2019.05.036. Epub 2019 May 25.
Diosgenyl 2-amino-2-deoxy-β-d-glucopyranoside is a semisynthetic saponin with antimicrobial and antitumor activities. To search for more effective analogues, N-aminoacyl and N-hydroxyacyl derivatives of this saponin were synthesized conventionally and with microwave assistance, and tested against the human pathogenic fungi and Gram-positive and Gram-negative bacteria. None of the tested compounds exhibit activity against Gram-negative bacteria. Almost all of the synthesized N-aminoacyl saponins exhibit antifungal activity and act effectively against Gram-positive bacteria, some better than the parent compound. The best acting saponins are the same size and possess sarcosine or l- or d-alanine attached to the parent glucosaminoside. Shorter and longer aminoacyl residues are less advantageous. d-Alanine derivative is the most effective against Gram positive bacteria. Structure-activity relationship (SAR) analysis indicates that the free α-amino group in aminoacyl residue is necessary for antimicrobial activities of the tested saponins. (N-Acetyl)aminoacyl and N-hydroxyacyl analogs are inactive. Measurements of the hemolytic activities demonstrate that the best acting saponins are not toxic towards human red blood cells.
薯蓣皂苷配基 2-氨基-2-脱氧-β-D-吡喃葡萄糖苷是一种具有抗菌和抗肿瘤活性的半合成皂苷。为了寻找更有效的类似物，本研究通过常规方法和微波辅助方法合成了该皂苷的 N-氨酰基和 N-羟酰基衍生物，并对其进行了抗人体致病真菌和革兰氏阳性菌和革兰氏阴性菌的测试。测试的化合物均没有表现出对革兰氏阴性菌的活性。几乎所有合成的 N-氨酰基皂苷都具有抗真菌活性，对革兰氏阳性菌有很好的作用，一些比母体化合物更好。作用最好的皂苷与母体葡萄糖胺糖苷具有相同的大小，并具有连接到母体葡萄糖胺糖苷上的肌氨酸或 L-或 D-丙氨酸。较短和较长的氨酰基残基则不太有利。D-丙氨酸衍生物对革兰氏阳性菌的作用最强。构效关系（SAR）分析表明，测试皂苷中氨基酰基残基中的游离α-氨基基团对于其抗菌活性是必需的。（N-乙酰基）氨酰基和 N-羟酰基类似物没有活性。溶血活性的测量表明，作用最好的皂苷对人红细胞没有毒性。
