Synthesis Of Novel1,3,4-Oxadiazol And Pyrazol Derivatives Bearing Rhodanine Moieties As Potential Antibacterial Agents

There has been a significant increase in the development of multidrug resistance (MDR) in bacteria in recent years, which has been linked closely to the abuse of antibiotics and antibacterial chemicals. The antibiotic resistance is becoming increasing a serious problem as the spectrum of bacteria that are sensitive to drugs becomes ever narrower, and the effect of combined medications becomes worse and worse. Bacterial infections are becoming increasingly difficult to treat as a result of the emergence of multidrug resistant pathogenic bacteria, with the number of infections progressing into deadly diseases and previously incogitable losses growing in number. There is therefore an urgent need for the development of novel antimicrobial agents. In this paper, we know1,3,4-oxadiazole and pyrazol structure represents a key structural motif in heterocyclic chemistry and occupies a prominent position in antimicrobial agents, with some of its derivatives showing good activity against bacteria. Rhodanine heterocyclic ring derivatives exhibit a broad spectrum of biological activities, including their application as antidiabetic drugs and antitubercular agents. According to the merging principle of drug design, we designed and synthesized two novel series1,3,4-oxadiazol derivatives compounds bearing rhodanine moieties as potential antibacterial agents using a structure-based design strategy with compounds A and B being used as the lead compounds, and three novel series of novel pyrazol derivatives bearing rhodanine moieties as potential antibacterial agents using a structure-based design strategy with compounds C and D being used as the lead compounds. All target compounds were evaluated their anti-bacterial activities. The majority of compounds showed broad-spectrum inhibitory activities against both Gram-positive and Gram-negative bacteria with minimum inhibitory concentration (MIC) values in the range of1-64μg/mL. The activity of compound6c was the more potent with MIC values of1μg/mL against the MRSA (3167and3506) strains than those of gatifloxacin, oxacillin, and norfloxacin. Compared to the previously reported rhodanine derivatives, rhodanine derivatives3a-k exhibited an inhibition against Gram-negative strains, among which compounds3showed moderate activities against the Gram-negative bacteria (E. coli1924) with MIC values of16μg/mL. Among these compounds,13c showed the most potent with MIC values of1μg/mL, the activity was to be equivalent to moxifloxacin’s and greater than those of gatifloxacin, oxacillin and norfloxacin against the MRSA (3167 and3506) strains. Among which compounds13and15showed best activities against the Streptococcus mutans3065strains with MIC values of1μg/mL. In this paper, forty-four target compounds structures were determined by analytical and spectral (1H NMR,13C NMR, MS, FTIR) methods.