Analysis of antimicrobial and anticancer activity of quinoxaline derivatives, evaluation of their toxicity, pharmacokinetic properties and structure – activity relationship

The Aim of the Research: To evaluate the structure influence on antimicrobial and anticancer activity of quinoxaline derivatives and identify the most promising compounds for the further development. Objectives: 1. To test antimicrobial (antibacterial and antifungal) activity of quinoxaline derivatives in vitro. 2. To test anticancer activity of quinoxaline derivatives in vitro. 3. To establish relationship between structure and antimicrobial, also anticancer activity. 4. To evaluate toxicity and pharmacokinetic properties of quinoxaline derivatives in silico. 5. To identify the most promising quinoxaline derivatives with reference to experimental results. Methods. Antimicrobial activity was tested in vitro using three different methods: serial dilution in agar, in liquid broth, and diffusion into agar. Anticancer activity was investigated by evaluating cell viability using MTT assay. Structure-activity relationship was evaluated from analysis of experimental data. Toxicity and pharmacokinetic properties were predicted by using ACD/I-Lab program. Results. The most promising quinoxaline derivatives inhibited growth of Bacillus and Staphylococcus genus bacteria with 16 μM concentration, fungus Candida albicans with 22 μM concentration. The most active quinoxaline derivatives were active against human lung carcinoma A549 and glioblastoma U87 cell lines with concentrations of 0.5-10 μM. Some principles of structure – antimicrobial activity relationship were established: the most active compounds have phenyl ring in the second position with halogen or nitro group, in the sixth position they have halogen. Compounds without any groups in the sixth or seventh positions have narrow spectrum of antimicrobial activity. The most active anticancer compounds have phenyl ring with para nitro group in the second position. Low toxicity was predicted for the most active compounds. Also, their bioavailability was predicted to be more than 70 percent. Conclusions. Quinoxaline derivatives are promising as antimicrobial and anticancer agents because they exhibit low toxicity and are advantageous in their pharmacokinetic properties