Synthesis And Antibacterial Evaluation Of Rhodanine-Drived 5-Aryl-1,2,4-Triazole-3-Thione, Amino-Guanidine And 3-Amine-1,2,4-Triazole Derivatives

The deaths of bacterial infection account for a significant proportion in total number of dead population in the world. Although there has been a plenty of antibacterial drugs have already being applied to clinical, while because of the emergence of new infectious diseases and the increasing number of multi-drug resistant microbial pathogens in view of the existing drugs gave rise to bacterial infections are becoming increasingly difficult to treat, this problem has draw the global attention. Therefore, the research of new antibacterial agents that solve the problem is very urgent. In this paper, we know 4-amino-5-aryl-1, 2, 4-triazole-3-thione-derived compounds with a variety of different pharmacological activities, including antibacterial, antispasmodic, anti-inflammatory, platelet aggregation resistance. And rhodanine heterocyclic ring is an active intermediate which exhibit antibacterial activity. According to the merging principle of drug design, we designed and synthesized three novel series 4-amino-5-aryl-1,2, 4-triazole-3-thione derivatives containing a rhodanine as potential antibacterial agents using a structure-based design strategy with compounds A and B being used as the lead compounds. In accordance with reported literature, we know the amino-guanidine group is a very important alkalinous active group and its derivatives show good activity against bacteria,1, 3, 4-oxadiazole and piperazine structures play a major role in heterocyclic chemistry and the research of antimicrobial agents. With an intention to synergise the antibacterial activity of amino-guanidine and heterocyclic, study the influence on antibacterial activity of amino-guanidine cyclization (3-amine-1, 2, 4-triazole). Three series of hybrid compounds possessing both amino-guanidine and heterocyclic moieties, a series of amino-guanidine cyclization derivatives were designed and synthesized. All of the compounds were evaluated for their anti-bacterial activities. In the series of rhodanine derivatives, some compounds showed good antibacterial activities against both Gram-positive and Gram-negative bacteria. Compound 5f exhibited good antibacterial activity against Gram-negative bacteria(Escherichia coli 1924), and Candida albicans 7535 with MBC values of 8 μg/mL. In the series of amino-guanidine derivatives, the majority of compounds showed broad-spectrum antibacterial activities against both Gram-positive and Gram-negative bacteria with MBC values in the range of 1-64 μg/mL (including multidrug-resistant clinical isolates and fungus). Among these compounds,19e and 19f with MBCs value in the range of 1-2 μg/mL against MRSA (3167 and 3506) strains and QRSA (3505 and 3519) strains were better than those of gatifloxacin, moxifloxacin. Moreover,19e and 19f as well as exhibited potent antifungus with MIC values of 1 μg/mL against Candida albicans 7535 and were equivalent to the standard drug fluconazole.