Zeynep ÖZDEMİR, Mehmet Abdullah ALAGÖZ, Alp Giray AKDEMİR, Azime Berna ÖZÇELİK, Mehtap UYSAL, Berrin ÖZÇELİK

Studies on a novel series of 3(2H)-pyridazinones: Synthesis, molecular modelling, antimicrobial activity

Efforts to develop new potent and effective antimicrobial compounds with lower side effects areimportant not only for controlling serious infections but also for cancer, surgical operations, and preventing possibleinfections which are related to other threats. Therefore, it is getting more important to develop new antibacterial andantifungal compounds with wide spectrum, systemic effect and lower side effects. In this study eight new 3(2H)-pyridazinone derivatives were synthesized and their antimicrobial activities were evaluated by using brothmicrodilution method agains two Gr (+) (Staphylococcus aureus, Enterococcus faecalis), two Gr (-) bacteria (Pseudomonasaeruginosa, Escherichia coli) and three yeasts like fungi (Candida albicans, Candida krusei). Compound D2a had the bestantibacterial activity among the synthesized compounds. All compounds were more effective against the fungus thanthe bacteria. In this study, we performed molecular modelling studies to provide in depth understanding of their CYP51inhibition. Antifungal susceptibility tests against standard Candida spp. including C. albicans revealed D2aas highlyactive compound. The molecular docking studies showed similarities in binding interactions in active site gorges of theenzymes with known inhibitors, such as VT1, fluconazole.

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