A new efficient domino approach for the synthesis of coumarin-pyrazolines as antimicrobial agents targeting bacteriald-alanine-d-alanine ligase

Abstract

The inhibition of d-alanine-d-alanine ligase (Ddl) prevents bacterial growth, which makes this enzyme an attractive and viable target in the urgent search for novel effective antimicrobial drugs.

Design, synthesis and in vivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA)

“…Coumarins are well known antibacterial candidates [42][43][44][45][46][47][48], acting via different mechanisms. These include topoisomerase II DNA (gyrase) [49] or D-alanine-D-alanine ligase (DdlB) [50] inhibition, cell membrane integrity [51], or cytochrome biosynthesis disruption [52]. Coumarins, naturally occurring and/or synthetic, also show remarkable pharmacological properties as anticoagulants [53,54], anti-inflammatory [55], antioxidant [56], antiplatelet [57], anticarcinogenic [58][59][60][61][62][63] and antifungal agents [64].…”

An Update of Synthetic Approaches and Structure‐Activity Relationships of Various Classes of Human MAO‐B Inhibitors

“…Pyrazoline scaffold possess well recognized antidepressant and anticonvulsant properties [148–150] . Additionally, it also has been served for antihypertensive, anti‐inflammatory, MAO enzyme inhibition [151] and antimicrobial potential [152] in recent years. Therefore, it could be taken as lead molecule to design some novel compounds with better inhibitory potential.…”

Coumarin‐containing hybrids and their antibacterial activities

“…The inhibition of d ‐alanine– d ‐alanine ligase could prevent bacterial growth, so this enzyme is an attractive and viable target in the development of novel antibacterial agents. [ 58,59 ] The SAR study of coumarin–pyrazoline hybrids 19 (half‐maximal inhibitory concentration/IC 50 : 106 to >400 µM) indicated that hydroxyl, methyl, and methoxy groups at the para and meta position of phenyl ring (R 2 position) increased the inhibition activity against d ‐alanine– d ‐alanine ligase, whereas the introduction of phenyl ring into pyrazoline moiety (R 1 position) led to a loss of activity. [ 58 ] In particular, hybrids 19a,b (IC 50 : 106 and 111 µM) with the highest activity against d ‐alanine– d ‐alanine ligase also possessed promising activity (MIC: 14–40 µg/ml) against E. coli and S. aureus , and the activity was on the same level with that of d ‐cycloserine (MIC: 16 and 32 µg/ml).…”