Clustering analysis of antibacterial compound chemical space

Vsi smo se že vsi vsaj enkrat soočili z bakterijsko okužbo, katero zdravljenje je potekalo z antibiotiki, ki smo ga v diplomskem delu uporabljali kot sinonim za protibakterijske učinkovine. Protibakterijske učinkovine se od ostalih zdravil razlikujejo predvsem po drugačnih fizikalno kemijskih lastnostih, delovanju, cilju delovanja, spektru delovanja in uporabi. Zlati dobi razvoja antibiotikov je zaradi vse hitrejše odpornosti bakterij sledila temačna doba, v kateri farmacevtska podjetja zaradi negotovosti in dragega razvoja niso želela vlagati v razvoj antibiotikov. Raje so se posvečala zdravilom, ki so jim predstavljala večjo gotovost in boljši zaslužek. Tako je bakterijska rezistenca postala ena največjih globalnih težav javnega zdravstva v 21. stoletju. Bolj kot na sam razvoj novih antibiotikov smo se osredotočili na predstavitev mehanizmov bakterijske rezistence in predvsem iskali rešitve kako se soočiti z bakterijam. Preučili smo kemijski prostor glede na izračunani set kemijskih deskriptorjev. Nato pa izvedli kemoinformacijsko analizo gruč in ugotovili, da poleg izračunanega za uspešno kvalifikacijo potrebujemo tudi strukturne informacije. Pri analizi kemijskega prostora smo opazili, da sta kemijska prostora protibakterijskih učinkovin in ostalih zdravil različna. Rezultati bodo koristili pri nadaljnji kemijski analizi in razvoju novih antibiotikov. Edinstven pristop pri razvoju zdravil v zgodnjih fazah predstavlja kemoinfomatika, ki bo v prihodnosti predstavljala ključen dejavnik, ki bo prihranil čas in denar.All of us have faced a bacterial infection at least once. It was treated with antibiotics, which we used in our bachelor’s thesis as a synonym for antibacterial active substances. Antibacterial active substances differ from other medicines mainly due to different physicochemical properties, action, purpose of action, spectrum of action, and application. The golden age of antibiotic development was followed by a dark age due to increasingly rapid bacterial resistance. In this dark age, pharmaceutical companies did not want to invest in antibiotic development due to uncertainty and expensive development. They preferred to devote themselves to medicines which enabled them greater certainty and better earnings. Thus, bacterial resistance has become one of the biggest global public health threats of the 21st century. More than on the development of new antibiotics, we focused on the presentation of the mechanisms of bacterial resistance and, above all, sought solutions to deal with bacteria. We examined the chemical space according to the calculated set of chemical descriptors. Then, we performed a cheminformatics analysis of the clusters and ascertained that, in addition to the calculated ones, we also need structural information for a successful qualification. While analyzing the chemical space, we noticed that the chemical spaces of antibacterial agents and other drugs are different. The results will be useful for further chemical analysis and the development of new antibiotics. Cheminformatics represents a unique approach to drug development in the early stages. It will be a key factor that will save time and money in the future