Abstract

Background: Microbial infections have been the major cause of morbidity and mortality for the centuries and continue to present the formidable challenge to the human health. Several studies have been performed to explore the antimicrobial potential of various synthesized chalcone derivatives. The morpholine derivatives are also gaining considerable importance due to diverse biological activities. Hybridization of morpholine and chalcone moiety together can be the useful approach for the development of new effective antimicrobial agents.

Methods: A new series of morpholine based heterocyclic diazenyl chalcones (MD1-MD21) was synthesized, characterized and evaluated for antimicrobial potential by tube dilution and agar diffusion methods. The most active derivatives were also evaluated for cytotoxicity towards mouse fibroblast cell line (L929) and the human lung cancer cell line (A549) and for haemolysis to check the toxicity on human red blood cells.

Results: MD-6 was found highly active against different microbial strains, particularly S. typhi, E. coli, A. niger and C. albicans having the MIC in the range of 1.95 µg/ml to 3.91 µg/ml. MD-9 and MD-21 were also found to have good antimicrobial activity. The most active diazenyl derivatives exhibited very low cytotoxicity towards L929 cell line (IC50 ranges from 360 µg/ml - 902.3 µg/ml) and A549 cell line (IC50 ranges from 35.42 µg/ml - 216.4 µg/ml) as compared to the standard drug 5-FU (IC50 ranges from 1 µg/ml - 2 μg/ml) against these cell lines. The active derivatives showed haemolysis of 10-15% up to 150 µg/ml concentration.

Conclusion: MD-6, MD-9 and MD-21 were found to be most active antimicrobial agents. These derivatives demonstrated high safety profile by exhibiting very low cytotoxicity and also revealed their safety for human blood cells with haemolysis of 0.2-5.5% at their antimicrobial concentration.

Keywords: Chalcones, antimicrobial, diazenyl, cytotoxicity, hemolysis, morpholine.

Graphical Abstract