Design, synthesis and biological evaluation of novel Schiff base-bridged tetrahydroprotoberberine triazoles as a new type of potential antimicrobial agents12. Issue 5 (6th March 2017)

• Record Type: Journal Article
• Authors: Duan, Jun-Rong; Liu, Han-Bo; Jeyakkumar, Ponmani; Gopala, Lavanya; Li, Shuo; Geng, Rong-Xia; Zhou, Cheng-He
• Is Part Of: MedChemComm. Volume 8:Issue 5(2017)
• Page Start: 907
• Page End: 916
• Publication Date: 2017-03-06
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c6md00688d
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : Synthesis of a series of Schiff base-bridged tetrahydroprotoberberine triazoles as a new type of potential antimicrobial agents, and preliminary interactions with DNA indicated the possible interaction mechanism. Abstract : A series of novel Schiff base-bridged tetrahydroprotoberberine (THPB) triazoles were designed, synthesized and characterized for the first time. Antimicrobial assay showed that some of the prepared compounds exerted stronger antibacterial and antifungal activities than the reference drugs. Especially, THPB triazole7a gave low MIC values of 0.5, 1 and 2 μg mL −1 against B. yeast, M. luteus and MRSA, respectively. Further experiments indicated that the highly active molecule7a was able to rapidly kill the MRSA strain and did not trigger the development of bacterial resistance even after 14 passages. The preliminary exploration for the antimicrobial mechanism revealed that compound7a could effectively intercalate into calf thymus DNA to form a7a –DNA supramolecular complex, and its Zn 2+ complex had the ability to directly cleave pUC19 DNA, which suggested that compound7a might be a potentially dual-targeting antibacterial molecule. It was also found that compound7a could be efficiently stored and carried by human serum albumin (HSA), and the hydrophobic interactions and hydrogen bonds played important roles in the transportation of HSA to the active molecule7a .