Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia; Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai, India.
Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, India; Centre for Advanced Studies in Botany & Centre for Herbal Sciences, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.
Bioorg Chem. 2019 Jul;88:102920. doi: 10.1016/j.bioorg.2019.102920. Epub 2019 Apr 9.
A series of novel covalent cholesterol-spiro pyrrolidine/pyrrolizidine heterocyclic hybrids possessing biologically active oxindole, indanedione, and acenaphthylene-1-one have been synthesized by the reaction of C3-β-cholesteroalacrylate with heterocyclic di- and tri-ketones. All the sixteen compounds were obtained as a single isomer in good yield through a stereo- and regio- selective 1,3-dipolar cycloaddition methodology. Stereochemistry of the spiranic cycloadducts has been established by spectroscopic analysis and the regioselectivity outcome of the spiro adducts has been accomplished by DFT calculations at B3LYP/6-31G (d,p) level study. In vitro antibacterial activity of the newly synthesized cycloadducts were evaluated against highly pathogenic Gram-positive and Gram-negative bacteria and the most active compounds 5a, 13, and 14 underwent automated in silico molecular docking analysis in order to validate their effective orientation as a inhibitors bound in the active site of glucosamine-6-phosphate synthase (1XFF) enzyme by employing AutoDock Tools.
通过 C3-β-胆固醇丙稀酸与杂环二酮和三酮的反应，合成了一系列具有生物活性的氧化吲哚、茚满二酮和苊烯-1-酮的新型共价胆固醇螺吡咯烷/吡咯烷杂环杂合体。所有 16 种化合物都通过立体和区域选择性 1,3-偶极环加成方法以单一异构体高产率获得。通过光谱分析确定了螺环加成物的立体化学，通过 B3LYP/6-31G（d，p）水平研究的 DFT 计算确定了螺加合物的区域选择性结果。对新合成的环加成物进行了体外抗细菌活性评估，针对高度致病性革兰氏阳性和革兰氏阴性细菌，最有效的化合物 5a、13 和 14 进行了自动计算机分子对接分析，以验证它们作为抑制剂的有效取向，这些抑制剂通过使用 AutoDock Tools 结合在葡萄糖胺-6-磷酸合酶（1XFF）酶的活性部位。
