SYNTHESIS, MOLECULAR DOCKING AND in-vitro ANTIMICROBIAL ACTIVITY STUDY OF IMINODIHYDROFURANS CONTAINING 4-THIAZOLIDINONE RING

Infections caused by microbes are a major cause of death worldwide. The increasing resistance of various pathogenic bacteria, including E. coli, S. aureus and Candida fungi, to antibiotics and antifungals has become a major public health problem in recent years. The limited number of antibiotics for the treatment of infections and the continuous development of resistance to the used antimicrobial and antifungal drugs pose a serious challenge. The discovery of new, safe and highly effective antibacterial and antifungal compounds against pathogens is very urgent. 2-Imino-2,5-dihydrofurans are N-containing analogs of O-containing biologically active compounds. Considering the enormous biological potential of 2-oxo-2,5-dihydrofuran and 4-thiazolidinone derivatives, synthetic compounds containing iminodihydrofuran and 4-thiazolidinone rings were studed for antibacterial and antifungal activities in silico and in vitro. We synthesized compounds ethyl 2-(4-oxo-2-((4-methyl-5,5-dialkyl-3-(alkyl(aryl, benzyl, cycloalkyl)carbamoyl)furan-2(5H)-ylidene)hydrazono)thiazolidin-5-ylidene)acetate 3a-3i and 2-(4-oxo-2-((4-methyl-5,5-dialkyl-3-(alkyl(aryl, benzyl, cycloalkyl)carbamoyl)furan-2(5H)-ylidene)-hydrazono)thiazolidin-5-yl)acetic acid 5a-5i comprising iminodihydofuran and thiazolidinone rings by subsequent Michael addition/heterocyclization reaction from iminodihydrofuran thi-osemicarbazones. Compounds 2-(4-oxo-2-((4,5,5-trimethyl-3-carbamoyl)furan-2(5H)-ylidene)hydrazono)thiazolidin-5-yl)acetic acid (5a), 2-(4-oxo-2-((4,5,5-trimethyl-3-phenylcarbamoyl)furan-2(5H)-ylidene)hydrazono)thiazolidin-5-yl)acetic acid (5d), 2-(4-oxo-2-((4,5,5-trimethyl-3-benzylcarbamoyl)furan-2(5H)-ylidene)hydrazono)thiazolidin-5-yl)acetic acid (5g), 2-(4-oxo-2-((4-methyl-5,5-penthamethylene-3-benzylcarbamoyl)furan-2(5H)-ylidene)hydrazono)thiazolidin-5-yl)acetic acid (5h) have pronounced antimicrobial activity against 3 pathogenic microorganisms. The results indicated that the tested organisms expe-rienced a noticeable inhibition of fungal and bacterial growth. The ADMET profiles indicate that these compounds, particularly 2-(4-oxo-2-((4-methyl-5,5-penthamethylene-3-benzylcarbamoyl)furan-2(5H)-ylidene)hydrazono)thiazolidin-5-yl)acetic acid (5h) with the highest human intestinal absorption, possess favorable characteristics for further optimiza-tion and development. Although they exhibit hepatotoxicity, refining their pharmacokinetic properties is essential for advancing these hit compounds as potential antimicrobial agents.