Chemical Attachment of 5-Nitrosalicylaldimine Motif to Silatrane Resulting in an Organic–Inorganic Structure with High Medicinal Significance

Abstract

Two chemical motifs of interest for medicinal chemistry, silatrane as 1-(3-aminopropyl) silatrane (SIL M), and nitro group attached in position 5 to salicylaldehyde, are coupled in a new structure, 1-(3-{[(2-hydroxy-5-nitrophenyl)methylidene]amino}propyl)silatrane (SIL-BS), through an azomethine moiety, also known as a versatile pharmacophore. The high purity isolated compound was structurally characterized by an elemental, spectral, and single crystal X-ray diffraction analysis. Given the structural premises for being a biologically active compound, different specific techniques and protocols have been used to evaluate their in vitro hydrolytic stability in simulated physiological conditions, the cytotoxicity on two cancer cell lines (HepG2 and MCF7), and protein binding ability—with a major role in drug ADME (Absorption, Distribution, Metabolism and Excretion), in parallel with those of the SIL M. While the latter had a good biocompatibility, the nitro-silatrane derivative, SIL-BS, exhibited a higher cytotoxic activity on HepG2 and MCF7 cell lines, performance assigned, among others, to the known capacity of the nitro group to promote a specific cytotoxicity by a “activation by reduction” mechanism. Both compounds exhibited increased bio- and muco-adhesiveness, which can favor an optimized therapeutic effect by increased drug permeation and residence time in tumor location. Additional benefits of these compounds have been demonstrated by their antimicrobial activity on several fungi and bacteria species. Molecular docking computations on Human Serum Albumin (HSA) and MPRO COVID-19 protease demonstrated their potential in the development of new drugs for combined therapy.

New 3-Aminopropylsilatrane Derivatives: Synthesis, Structure, Properties, and Biological Activity

“…3-Aminopropylsilatrane 1 was synthesized according to the published procedure [ 24 , 25 , 26 , 46 ]. The synthesis of new silatrane derivatives 2–7 is shown in Scheme 3 .…”

“…Over the last few decades, bioorganosilicon chemistry has witnessed a number of breakthrough results [17,18]. This is also true of intra-complex compounds of pentacoordinated silicon and silatranes R-Si(OCH 2 CH 2 ) 3 N. It should be emphasized that, depending on the R substituent and as a result of the presence of an intramolecular coordinate bond (Si←N) and a unique tricyclic structure, silatranes exhibit high and diverse physiological and pharmacological activities, including antifungal, antimicrobial, antiparasitic, and anticancer properties [19][20][21][22][23][24][25][26].…”

New Functional Alkoxysilanes and Silatranes: Synthesis, Structure, Properties, and Possible Applications

“…[ 12 , 13 ]. They are efficient antifungal ( Aspergillus fumigatus , Penicillium chrysogenum , Fusarium ) [ 14 ], antimicrobial ( Enterococcus durans , Bacillus subtilis , Escherichia coli , Pseudomonas aeruginosa , Hepatitis B virus ) [ 15 , 16 , 17 ], antiparasitic ( Giardia lamblia , Trichomonas vaginalis ) [ 18 ] and anticancer (adenocarcinoma, hepatocarcinoma, melanoma) agents [ 19 , 20 ] and potential drugs [ 21 ].…”