Silyl Modification of Biologically Active Compounds. 14. Organosilicon Lipid-like Derivatives of Hydroxyethyl Tetrahydro(iso)quinoline and Thiazole with Antitumour, Antibacterial and Antifungal Properties

Purpose

A series of novel lipid-like O- and N-(3-trimethylsilyl)propyl derivatives of N-(2-hydroxyethyl)-1,2,3,4-tetrahydroquinoline, -tetrahydroisoquinoline and 5-(2-hydroxyethyl)-4-methyl-1,3-thiazole have been obtained in order to facilitate penetration of biologically active small molecules through the plasma membrane and/or to enable their immobilization on the surface of magnetic nanocarriers for drug delivery application.

Methods

The synthesized compounds have been characterized by ¹H, ¹³C and ²⁹Si NMR spectroscopy and mass-spectrometry, evaluated for cytotoxicity on monolayer human fibrosarcoma HT-1080 and mouse hepatoma MG-22A tumour cell lines and normal mouse fibroblasts NIH 3T3, and screened for antimicrobial activity against gram-positive and gram-negative bacterial and fungal strains. Their inhibitory action towards topoisomerase II has also been investigated.

Results

The obtained organosilicon compounds possessed high selective cytotoxicity (LC ₅₀<1 µg ml ^-1) towards tumour cells and NO-induction ability, exhibited strong antimicrobial activity with MIC and MBC/MFC values of 0.5–32 µg ml^-1 for the most active ones.

Conclusions

The lipid-like organosilicon derivatives of hydroxyethyl tetrahydro(iso)quinoline and thiazole exhibit an interesting combination of inhibitory activities towards tumours and bacterial cells and fungi. The pharmacological effect ranged from moderate to significant and increased upon quaternization. Compounds possessing high cytotoxicity and strong antibacterial and antifungal activity can be further developed as potential monotherapeutic agents for treatment infections in cancer patients instead of combination anticancer and anti-infective pharmacotherapy.