Investigation of some bioactive properties of α-aminophosphonate compounds and Schiff bases

In this thesis, firstly, the antioxidant capacities of Schiff base (7-11) and bis-α-aminophosphonate derivatives (13-16) were determined using reduction, radical scavenging and metal chelation methods. It has been observed that Schiff bases have higher metal chelating activity than bis-α-aminophosphonate derivatives. In addition, in vitro and in silico studies were carried out to determine the inhibition effects of these molecules on carbonic anhydrase isoenzymes (hCA I and II) and acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase and tyrosinase enzymes. Enzyme inhibition results showed that bis-α-aminophosphonate derivatives were better inhibitors than Schiff bases against the studied enzymes. According to the experimentally obtained IC50 values, the best inhibitors are found to be molecule 15 for AChE (IC50 = 6,48 µg/mL), molecule 13 for BChE (IC50 = 49,51 µg/mL), molecule 16 for α-glucosidase (IC50 = 32,54 µg/mL), and molecule 9 (IC50 = 187,34 µg/mL) for tyrosinase. It was observed that the experimental results and molecular docking results were in agreement with each other. Electronic structures of molecules and global reactivity parameters were calculated by using density functional theory (DFT) method, with B3LYP functional and cc-pVDZ basis set. In addition, in silico ADME studies were also carried out to investigate the physicochemical, lipophilicity, solubility, pharmacokinetics, drug similarity and medicinal chemistry properties of all molecules. The antibacterial activity properties of the molecules against eleven different microorganisms were evaluated. It was found that Schiff base derivatives showed very strong antibacterial effects against S. epidermidis and A. baumannii bacteria, and bis-α-aminophosphonate derivatives showed very strong antibacterial effects against S. epidermidis, S. dysenteriae and A. baumannii bacteria, compared to the positive control ampicillin.