Identification of dominant scaffolds in antibacterial compounds

Protibakterijske učinkovine predstavljajo eno izmed najširše zastopanih zdravil. V drugi polovici 20. stoletja so antibiotiki doživeli razcvet, vendar pa je svet kmalu spoznal pereč problem: bakterijsko rezistenco. Hitra rast bakterijske odpornosti na antibiotike tudi dandanes zastavlja številne izzive pri odkrivanju novih vrst učinkovin, ki bi rešile to težavo. Namen tega diplomskega dela je predstaviti probleme, s katerimi se srečujemo pri razvoju novih protibakterijskih učinkovin ter prikazati možne rešitve. V diplomskem delu smo opisali terapijo bakterijskih okužb, razvoj rezistence in predstavili obstoječe razrede antibiotikov. Spoznali smo se z metodami analize struktur učinkovin in z njihovim vplivom na lastnosti same molekule. V nalogi smo analizirali skelete protibakterijskih in ostalih učinkovin, jih primerjali med sabo, predstavili najpogosteje zastopane skelete in jih umestili v kemijski prostor. Rezultati so pokazali, da se strukture skeletov in sam kemijski prostor dveh preučevanih skupin zdravil razlikujeta. Analizo smo razširili še na Gram-pozitivne in Gram-negativne organizme, ter tudi v tem primeru našli razlike v strukturi in porazdelitvi skeletov po kemijskem prostoru.Antibacterial compounds represent one of the most important types of therapeutics. In the second half of the 20th century, antibiotics flourished, but the world soon faced the problem of bacterial resistance. The rapid growth of bacterial resistance even today poses many challenges in discovering new types of antibacterial compounds. The purpose of this work was to present some of the problems in the novel antibacterial development. In this work, we described the therapy of bacterial infections, the development of resistance and presented the existing classes of antibiotics. We performed analysis of the chemical structures of antibacterials and their influence on the physico-chemical properties. Moreover, we analyzed antibacterial scaffolds and scaffolds of drugs for other indications. Most common scaffolds of both analyzed groups of registered drugs are presented and compared. We can conclude that molecular scaffolds and relating chemical spaces significantly differ between each other. The analysis was extended to antibacterials acting against Gram-positive and Gram-negative organisms, and even in this case, we observed differences in the structure and distribution of scaffolds in the chemical space