| Autor: |
Zaltariov MF; Inorganic Polymers Department, 'Petru Poni' Institute of Macromolecular Chemistry, Aleea Gr. Ghica Voda 41 A, 700487 Iasi, Romania., Turtoi M; Medical and Pharmaceutical Bionanotechnologies Laboratory, Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, B.P. Hasdeu 8, 050568 Bucharest, Romania., Peptanariu D; Centre of Advanced Research in Bionanoconjugates and Biopolymers, 'Petru Poni' Institute of Macromolecular Chemistry, Aleea Gr. Ghica Voda 41 A, 700487 Iasi, Romania., Macsim AM; NMR Laboratory, 'Petru Poni' Institute of Macromolecular Chemistry, Aleea Gr. Ghica Voda 41 A, 700487 Iasi, Romania., Clima L; Centre of Advanced Research in Bionanoconjugates and Biopolymers, 'Petru Poni' Institute of Macromolecular Chemistry, Aleea Gr. Ghica Voda 41 A, 700487 Iasi, Romania., Cojocaru C; Inorganic Polymers Department, 'Petru Poni' Institute of Macromolecular Chemistry, Aleea Gr. Ghica Voda 41 A, 700487 Iasi, Romania., Vornicu N; Metropolitan Center of Research T.A.B.O.R, The Metropolitanate of Moldavia and Bukovina, 700066 Iasi, Romania., Ciubotaru BI; Inorganic Polymers Department, 'Petru Poni' Institute of Macromolecular Chemistry, Aleea Gr. Ghica Voda 41 A, 700487 Iasi, Romania., Bargan A; Inorganic Polymers Department, 'Petru Poni' Institute of Macromolecular Chemistry, Aleea Gr. Ghica Voda 41 A, 700487 Iasi, Romania., Calin M; Medical and Pharmaceutical Bionanotechnologies Laboratory, Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, B.P. Hasdeu 8, 050568 Bucharest, Romania., Cazacu M; Inorganic Polymers Department, 'Petru Poni' Institute of Macromolecular Chemistry, Aleea Gr. Ghica Voda 41 A, 700487 Iasi, Romania. |
| Abstrakt: |
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 M PRO COVID-19 protease demonstrated their potential in the development of new drugs for combined therapy. |
