subtilis. The parent compound carvacrol also exerted no activity against
Escherichia coli (Patil et al. 2010). The enzymatic conversions (glycosylation) of
carvacrol produced b-glucosides (B7) and b-gentiobiosides (B8) derivatives ameliorated the physicochemical properties and the pharmacokinetic profile of carvacrol (Shimoda et al. 2006). The flavor, fragrance, and antimicrobial properties
were improved by introducing hydroxymethyl and allyl groups in carvacrol (19-22)
(Lupo et al. 2000) but the bioactivity against all the tested Gram-negative bacteria
was decreased and antimicrobial activity on Gram-positive bacteria strains were
increased in respect to carvacrol. Ortho allyl carvacrol derivative showed the most
significant activity against Propionibacterium acnes but resistant against
Staphylococcus aureus. Introduction of saturated and unsaturated aliphatic side
chains and aromatic units produced ethers (23-28) and esters (29-32) derivatives
that possessed more potent antimicrobial response than carvacrol against Bacillus
megaterium, Bradyrhizobium japonicum, Bacillus polymyxa, and Bacillus substilits
(Nikumbh et al. 2003). Among ethers, the carboxymethyl derivative (28) and
among the esters, the phenylacetate derivative (30) were the most active antibacterial compounds. Development of 4-hydroxy-2-isopropyl benzene sulfonic acid
(31), potassium 4-hydroxy-2-isopropyl benzene sulfonate (32), and
5-isopropyl-2-methyl phenyl dodecanoate (33) derivatives of carvacrol (Fig. 13.4)
were synthesized with better physicochemical profiles and antimicrobial activity
(Bassanetti et al. 2017). The parent drug and synthesized compounds were tested
against Clostridium perfringens, Salmonella typhimurium, Salmonella enteritidis,
and Escherichia coli strains. These three analogs along with carvacrol exhibited
potent cytotoxicity against human colorectal carcinoma cell lines (HT-29) by
inhibiting the proliferation of the cancer cells (Bassanetti et al. 2017). Cacciatore
et al. (2015) synthesized a series of alkyl cysteine carvacrol derivatives by using the
co-drug strategy. The hydroxyl group of carvacrol was conjugated with the carboxyl portion of sulfur-containing amino acids via an ester bond. The in vitro
studies of all the derivatives showed low water solubility, good stability in an acidic
environment, in human and rat plasma, and a good permeability verified by
PAMPA-GI (parallel artificial gastrointestinal membrane permeability assay). (R)5-isopropyl-2-methyl phenyl 2-acetamido-3-(allylthio) propanoate (34) was found
to be the most active antibacterial compound (Fig. 13.5). The carvacrol sulfonamide derivatives (35-43) (Fig. 13.5) were synthesized by inserting selected amines
at carvacrol aromatic ring previously treated with chlorosulfonic acid (De Oliveira
et al. 2016). The obtained sulfonamides were superior to carvacrol against selected
Staphylococcus aureus strains and able to reduce bacterial resistance. P-toluene
(35), p-fluorobenzene (37), and 4-amino-N-(thiazol- 2-yl) benzene sulfonamide
(42) groups containing carvacrol derivatives revealed antimicrobial activity at lower
concentration with lower MIC values (from 3.90 to 62.50 ppm) among the tested
compounds. The compound 4-hydroxy-2-isopropyl-5-methyl-N-(p-tolyl) benzene
sulfonamide (35) had a synergistic effect with erythromycin, and compound N(4-fluorophenyl)-4-hydroxy-2-isopropyl-5-methyl benzene sulfonamide (37)
showed a synergistic response when incorporated with ampicillin and tetracycline,
respectively (Marinelli et al. 2018).
454
A. Mondal et al.
Escherichia coli (Patil et al. 2010). The enzymatic conversions (glycosylation) of
carvacrol produced b-glucosides (B7) and b-gentiobiosides (B8) derivatives ameliorated the physicochemical properties and the pharmacokinetic profile of carvacrol (Shimoda et al. 2006). The flavor, fragrance, and antimicrobial properties
were improved by introducing hydroxymethyl and allyl groups in carvacrol (19-22)
(Lupo et al. 2000) but the bioactivity against all the tested Gram-negative bacteria
was decreased and antimicrobial activity on Gram-positive bacteria strains were
increased in respect to carvacrol. Ortho allyl carvacrol derivative showed the most
significant activity against Propionibacterium acnes but resistant against
Staphylococcus aureus. Introduction of saturated and unsaturated aliphatic side
chains and aromatic units produced ethers (23-28) and esters (29-32) derivatives
that possessed more potent antimicrobial response than carvacrol against Bacillus
megaterium, Bradyrhizobium japonicum, Bacillus polymyxa, and Bacillus substilits
(Nikumbh et al. 2003). Among ethers, the carboxymethyl derivative (28) and
among the esters, the phenylacetate derivative (30) were the most active antibacterial compounds. Development of 4-hydroxy-2-isopropyl benzene sulfonic acid
(31), potassium 4-hydroxy-2-isopropyl benzene sulfonate (32), and
5-isopropyl-2-methyl phenyl dodecanoate (33) derivatives of carvacrol (Fig. 13.4)
were synthesized with better physicochemical profiles and antimicrobial activity
(Bassanetti et al. 2017). The parent drug and synthesized compounds were tested
against Clostridium perfringens, Salmonella typhimurium, Salmonella enteritidis,
and Escherichia coli strains. These three analogs along with carvacrol exhibited
potent cytotoxicity against human colorectal carcinoma cell lines (HT-29) by
inhibiting the proliferation of the cancer cells (Bassanetti et al. 2017). Cacciatore
et al. (2015) synthesized a series of alkyl cysteine carvacrol derivatives by using the
co-drug strategy. The hydroxyl group of carvacrol was conjugated with the carboxyl portion of sulfur-containing amino acids via an ester bond. The in vitro
studies of all the derivatives showed low water solubility, good stability in an acidic
environment, in human and rat plasma, and a good permeability verified by
PAMPA-GI (parallel artificial gastrointestinal membrane permeability assay). (R)5-isopropyl-2-methyl phenyl 2-acetamido-3-(allylthio) propanoate (34) was found
to be the most active antibacterial compound (Fig. 13.5). The carvacrol sulfonamide derivatives (35-43) (Fig. 13.5) were synthesized by inserting selected amines
at carvacrol aromatic ring previously treated with chlorosulfonic acid (De Oliveira
et al. 2016). The obtained sulfonamides were superior to carvacrol against selected
Staphylococcus aureus strains and able to reduce bacterial resistance. P-toluene
(35), p-fluorobenzene (37), and 4-amino-N-(thiazol- 2-yl) benzene sulfonamide
(42) groups containing carvacrol derivatives revealed antimicrobial activity at lower
concentration with lower MIC values (from 3.90 to 62.50 ppm) among the tested
compounds. The compound 4-hydroxy-2-isopropyl-5-methyl-N-(p-tolyl) benzene
sulfonamide (35) had a synergistic effect with erythromycin, and compound N(4-fluorophenyl)-4-hydroxy-2-isopropyl-5-methyl benzene sulfonamide (37)
showed a synergistic response when incorporated with ampicillin and tetracycline,
respectively (Marinelli et al. 2018).
454
A. Mondal et al.