Carvacrol Codrugs: A New Approach in the Antimicrobial Plan

Abstract

ObjectiveThe increasing prevalence of antibiotic-resistant bacterial infections led to identify alternative strategies for a novel therapeutic approach. In this study, we synthesized ten carvacrol codrugs – obtained linking the carvacrol hydroxyl group to the carboxyl moiety of sulphur-containing amino acids via an ester bond – to develop novel compounds with improved antimicrobial and antibiofilm activities and reduced toxicity respect to carvacrol alone.MethodAll carvacrol codrugs were screened against a representative panel of Gram positive (S. aureus and S. epidermidis), Gram negative (E. coli and P. aeruginosa) bacterial strains and C. albicans, using broth microdilution assays.FindingsResults showed that carvacrol codrug 4 possesses the most notable enhancement in the anti-bacterial activity displaying MIC and MBC values equal to 2.5 mg/mL for all bacterial strains, except for P. aeruginosa ATCC 9027 (MIC and MBC values equal to 5 mg/mL and 10 mg/mL, respectively). All carvacrol codrugs 1-10 revealed good antifungal activity against C. albicans ATCC 10231. The cytotoxicity assay showed that the novel carvacrol codrugs did not produce human blood hemolysis at their MIC values except for codrugs 8 and 9. In particular, deepened experiments performed on carvacrol codrug 4 showed an interesting antimicrobial effect on the mature biofilm produced by E. coli ATCC 8739, respect to the carvacrol alone. The antimicrobial effects of carvacrol codrug 4 were also analyzed by TEM evidencing morphological modifications in S. aureus, E. coli, and C. albicans.ConclusionThe current study presents an insight into the use of codrug strategy for developing carvacrol derivatives with antibacterial and antibiofilm potentials, and reduced cytotoxicity.

Carvacrol and human health: A comprehensive review

“…Recent research has been carried out on CV as a potential codrug against bacterial biofilm. Ten CV codrugs have been synthesized by linking the CV hydroxyl group to the carboxyl moiety of sulphur‐containing amino acids via an ester bond (Figure ), developing novel compounds with improved antimicrobial and antibiofilm activities and reduced toxicity compared with CV alone (Cacciatore et al, ). Among these derivatives, all CV codrugs revealed successful antifungal activity against C. albicans ATCC 10231, but generally with lower potency than CV.…”

“…The novel CV codrugs showed no evidence of human blood hemolysis at their MIC values (below 50%) in cytotoxicity assay, except two codrugs (codrugs 8 and 9; MIC values over 50%). Further experiments performed using the most active CV codrug, that is, Ac‐Cys(allyl)‐CV, demonstrated higher antibacterial effect against the mature biofilm of E. coli ATCC 8739 compared with CV (Cacciatore et al, ).…”

“…Chemical structures of carvacrol codrugs 1 – 10 obtained by linking the carvacrol hydroxyl group to the carboxyl moiety of sulphur‐containing amino acids via an ester bond (Cacciatore et al, )…”

Carvacrol after status epilepticus (SE) prevents recurrent SE, early seizures, cell death, and cognitive decline

“…It has been used widely in the food industry as a flavoring and food preservative. Carvacrol has been shown to have bactericidal, fungicidal, and insecticidal activity . More recently it has been shown to have neuroprotective effects in both in vitro and in vivo animal models of cerebral ischemia, probably through inhibition of transient receptor potential cation subfamily M7 (TRPM7) channels .…”

“…Carvacrol has been shown to have bactericidal, fungicidal, and insecticidal activity. [1][2][3] More recently it has been shown to have neuroprotective effects in both in vitro and in vivo animal models of cerebral ischemia, [4][5][6][7] probably through inhibition of transient receptor potential cation subfamily M7 (TRPM7) channels. 6 TRPM7 channels are ubiquitously expressed transmembrane ion channels, which are constitutively active and suppressed by high intracellular concentrations of free magnesium and Mg 2+ ATP, 8 and so act as magnesium sensors.…”