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Abstract
The present investigation is concerned with the synthesis of a new series of 2-arylquinoline-4-carboxylic acid hydrazone-hydrazides (5a,b1-3,e1,2,d,f1-3,i ,h1,2,g1-3,j1-4) using an appropriate synthetic route. In addition a new series of 1,3,4-oxadizoles (7a,b,d,e,g,i,j) was synthesized from cyclization of the key intermediate thiosemicarbazides (6a,b,d,e,g,i,j), also a new series of 1,3,4-thiadizoles (8b,c,d,f,h,i,j) was synthesized from cyclization of the key intermediate quinoline-4-carboxylic acid (1b,c,d,f,h,i,j) or the synthetically accessible thiosemicarbazides (6,b,d,i,j). All the target hydrazones were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus as an example for Gram positive bacteria, Escherichia coli as an example for Gram negative bacteria, and Candida albicans as a representative of fungi. The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standards. Among the tested hydrazones, compounds having nitro substituent at the arylidene moiety showed the most potent antifungal as well as antibacterial activity against Escherichia coli. Compound 5j4 displayed an antifungal activity comparable to that of Nystatin. However, none of the hydrazones demonstrated any antibacterial activity against Staphylococcus aureus. On the other hand, the target oxadiazoles and thiadiazoles were evaluated against Staphylococcus aureus, Bacillus subtilis as examples for Gram positive bacteria, Escherichia coli, Salmonella typhimurium as examples for Gram negative bacteria, and Candida albicans, Saccharomyces cerevisiae as representative of fungi. The obtained results showed that all the tested oxadiazole and thiadiazoles lacked antibacterial activity against Bacillus subtilis, Escherichia coli and Salmonella typhimurium, while some compounds namely, 7d, 7g, 7j, 8b, 8d, 8f, 8h and 8j displayed antibacterial activity against Staphylococcus aureus. The 1,3,4-thiadiazoles 8d and 8h exhibited the most potent antibacterial activity with MIC values of 4 µg/mL. Furthermore, the results revealed that most of the compounds have antifungal activity against both Candida albicans and Saccharomyces cerevisiae. The 1,3,4-oxadiazoles 7g and 7j and the 1,3,4-thiadiazoles 8c and 8j showed weak activity against Candida albicans. On the other hand, nearly half of the tested compounds displayed activity against Saccharomyces cerevisiae with MIC values ranging from 16 to 64 µg/mL.
HyDROPhobicity of the all target compounds correlated weakly with their antibacterial and antifungal activities. The most potent compounds namely, 5b3, 5g2, 5g3, 5j3, 5j4 were assessed for hemolytic toxicity and found to be non-hemolytic up to a concentration of 100 µg/mL. In addition, the most potent compound 5j4 was evaluated for in vitro cytotoxic activity against various cancer cell lines. This compound was found to display no cytotoxic activity but rather it induces the proliferation rate of Hep-G2 cells.