Isoxazole derivatives of silatrane: synthesis, characterization, in silico ADME profile, prediction of potential pharmacological activity and evaluation of antimicrobial action

Abstract

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 (1H, 13C,29Si and 15N) 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 similar 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).

A review of recent synthetic strategies and biological activities of isoxazole

“…When compared to the conventional medicine gentamicin (MIC 25 and 50 μg/mL), Silatrane 3 with R = 4-MeOC 6 H 4 had a lower minimum inhibitory concentration (MIC 12. S C H E M E 5 6 Synthesis of a novel class of mono-and bisisoxazole-linked silatranes [76] L. Donovani [78]. In comparison with Miltefosine, the standard drug used in bioassays, some of the derivatives exhibited curiously improved inhibition of promastigote and amastigote stages of parasites.…”

“…The interaction of 3‐aminopropylsilatrane 1 and 3‐substituted 5‐chloro‐methylisoxazoles 2 yielded a novel class of mono‐ isoxazole‐linked silatranes 3 and bis‐isoxazole‐linked silatranes 4 as depicted in the Scheme 56 [76]. Preliminary antimicrobial activity testing of the produced silatranes against Enterococcus durans, Bacillus subtilis, E. coli , and Pseudomonas aeruginosa suggests that all tested samples are only active against gram‐positive bacteria.…”

3-Aminopropylsilatrane and Its Derivatives: A Variety of Applications

“…A series of novel organic–inorganic hybrids, combining one ( 16 ) or two ( 17 ) units of the isoxazole motif and one silatrane unit in a single molecule, were synthesized ( Figure 5 ) [ 51 ]. The screening of silatranes ( 16 ) and ( 17 ) for antimicrobial activity against Enterococcus durans , Bacillus subtilis , Escherichia coli , and Pseudomonas aeruginosa revealed that all the test samples were active only against Gram-positive microorganisms.…”

Prospects of the Use of Synthetic Biostimulants for the Development of Aquaculture of Whitefishes in Lake Baikal

“…В Иркутском институте химии СО РАН получен широкий ряд синтетических биологически активных соединений, названных «атраны» [11][12][13], в частности ряд арил-халькогенилацетатов трис(2-гидроксиэтил)аммония, названный «протатраны», с общей формулой ArХCH 2 CO 2 -• НN + (CH 2 СН 2 ОН) 3 (А), где Ar = арил; Х = S, SO, SO 2 , Se [14].…”