FULL PAPER Isoxazole derivatives of silatrane: synthesis, characterization, in silico ADME profile, prediction of potential pharmacological activity and evaluation of antimicrobial action Sergey N. Adamovich 1 | Evgeniy V. Kondrashov 1 | Igor A. Ushakov 1 | Nina S. Shatokhina 1 | Elizaveta N. Oborina 1 | Alexander V. Vashchenko 1 | Lydmila A. Belovezhets 1 | Igor B. Rozentsveig 1 | Francis Verpoort 2 1 A. E. Favorsky Irkutsk Institute of Chemistry, SB RAS, 1 Favorsky Street, Irkutsk, 664033, Russian Federation 2 Laboratory of Organometallics, Catalysis and Ordered Materials, State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, China Correspondence Sergey N. Adamovich, A. E. Favorsky Irkutsk Institute of Chemistry, SB RAS, 1 Favorsky Street, 664033, Irkutsk, Russian Federation. Email: mir@irioch.irk.ru Francis Verpoort, Laboratory of Organometallics, Catalysis and Ordered Materials, State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, China. Email: francis.verpoort@ghent.ac.kr A new family of mono- (3a-h) and bis- (4a-g) isoxazole-bridged silatranes has been synthesized by the reaction of 3-aminopropylsilatrane (1) and 3-substituted 5-chloro-methylisoxazoles (2a-h). The structure of the isoxazole- silatrane hybrids is characterized by elemental analysis, FT-IR, UV, NMR ( 1 H, 13 C, 29 Si and 15 N) spectroscopy, high-resolution mass spectrometry, and X-ray diffraction analysis. The in silico ADME (absorption, distribution, metabolism, excretion) assessment reveals that properties of mono-adducts (3a-h) are simi- lar to those of drugs obeyed to the Lipinski's rule. The calculated screening of potential pharmacological activity profiles (in silico PASS program) of isoxazole-silatranes shows that all synthesized compounds (both mono- and bis-substituted) may have high antitumor action, unlike starting isoxazoles. The preliminary screening of the synthesized silatranes for antimicrobial activity against Enterococcus durans, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa indicates that all test samples are active only against gram-positive microorganisms. Silatrane 3f displays minimal inhibitory concentration (MIC 12.5 and 6.2 μg ml -1 ) against E. durans and B. subtilis as compared with standard drug gentamicin (MIC 25 and 50 μg ml -1 ). KEYWORDS antimicrobial activity, hybrids, isoxazole, silatrane, X-ray crystallography 1 | INTRODUCTION Trialkanolamine organosilicon esters, silatranes XSi (OCHRCH 2 ) 3 N, belong to a widely known class of tricy- clic compounds of pentacoordinated silicon (with intra- molecular transannular Si  N dative bond). [1–4] The unique structure of silatranes imparts them original chemical and physical properties. Also, unlike other organosilicon compounds (siloxanes, silicones), silatranes possess amazing physiological activity. In this context, silatranes are of great applied interest. For example, the strong electron-donating effect of the silatranyl group ensures specific reactivity of silatranes. [1,2] Ionization of these compounds changes the geometry of their mole- cules (increased/decreased length of the Si  N bond). [5] This phenomenon can be used to design nanoscale Received: 9 June 2020 Revised: 28 July 2020 Accepted: 2 August 2020 DOI: 10.1002/aoc.5976 Appl Organomet Chem. 2020;e5976. wileyonlinelibrary.com/journal/aoc © 2020 John Wiley & Sons, Ltd. 1 of 12 https://doi.org/10.1002/aoc.5976