pathway (Yin et al. 2012). So overall carvacrol demonstrated potent anticancer
activity against a variety of carcinoma cell lines by inhibiting the proliferation of the
cells by apoptotic pathway triggered by activation of caspases, increased DNA
fragmentation (Koparal and Zeytinoglu 2003; Mehdi et al. 2011; Al-Fatlawi and
Ahmad 2014; Ozkan and Erdogan 2012). It also exhibited protective activity
against H 2 O 2 induced DNA damage (Slamenova et al. 2013; Llana-Ruiz-Cabello
et al. 2015; Ündeğer et al. 2009). The efficacy of carvacrol can further be improved
by preparing a carvacrol b-cyclodextrin inclusion complex, which exhibited higher
antiproliferative activity against prostate cancer cells (PC3), in comparison to free
carvacrol (Trindade et al. 2019).
13.11 Carvacrol Derivatives with Pharmacological
Activities
The structure-activity relationships of carvacrol indicated that the presence of OH
group and delocalized electrons cloud were responsible for the pharmacological
activities of carvacrol (1) (Fig. 13.4) (Ultee et al. 2002). Removal or replacement of
the hydroxyl group with methyl ether produces lesser active compound p-cymene
(2) and methyl ether derivative of carvacrol (3) due to the lower tendency to donate
protons than the hydroxyl group (Ben Arfa et al. 2006; Marinelli et al. 2018).
Carvacryl acetate (4) is an analog of carvacrol synthesized by refluxing carvacrol,
sodium acetate, and acetic anhydride. It was then subsequently purified and characterized [Ben Arfa et al. 2006]. Carvacrol was 28 times more potent than its
structural isomer (positional isomer) thymol (5) (2-isopropyl-5-methyl phenol)
against gram-positive and gram-negative bacteria like Mycobacterium tuberculosis,
Escherichia coli, Staphylococcus aureus, and Candida albicans. Menthol (6)
(2-isopropyl-5-methyl cyclohexanol), eugenol (7) (4-allyl-2-methoxyphenyl),
vanillin (8) (4-hydroxy-3-methoxy benzaldehyde) and 3-isopropyl-5-methyl phenol
(9) were equivalent potent as compared to thymol. Replacement of isopropyl group
of menthol with vinyl group produced neo isopulegol derivative (10) [2-methyl-5(prop-1-en-2-yl) cyclohexanol], which was twice more potent antimycobacterial
agent than menthol. 4-chloro-5-isopropyl-2-methyl phenol (11) is a 4-substituted
chloro derivative of carvacrol synthesized from carvacrol exhibited similar
antimycobacterial activity as that of 2-methyl-5-(prop-1-en-2-yl) cyclohexanol (10)
(Alokam et al. 2013).
The aim of the SAR study is to develop carvacrol derivatives with potent biological activity. Patil et al. (2010) suggested carvacryl derivatives were obtained by
the attachments of acetanilide or a-chloro acetanilide group with carvacrol via ether
bonds. Comparative antimicrobial studies between carvacryl ether derivatives and
carvacrol against Bacillus subtilis, Escherichia coli, Proteus vulgaris, and
Staphylococcus aureus. The phenyl derivative of carvacryl ether (12) provided a
little antimicrobial activity against Bacillus subtulis, and inactive against other
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A. Mondal et al.
activity against a variety of carcinoma cell lines by inhibiting the proliferation of the
cells by apoptotic pathway triggered by activation of caspases, increased DNA
fragmentation (Koparal and Zeytinoglu 2003; Mehdi et al. 2011; Al-Fatlawi and
Ahmad 2014; Ozkan and Erdogan 2012). It also exhibited protective activity
against H 2 O 2 induced DNA damage (Slamenova et al. 2013; Llana-Ruiz-Cabello
et al. 2015; Ündeğer et al. 2009). The efficacy of carvacrol can further be improved
by preparing a carvacrol b-cyclodextrin inclusion complex, which exhibited higher
antiproliferative activity against prostate cancer cells (PC3), in comparison to free
carvacrol (Trindade et al. 2019).
13.11 Carvacrol Derivatives with Pharmacological
Activities
The structure-activity relationships of carvacrol indicated that the presence of OH
group and delocalized electrons cloud were responsible for the pharmacological
activities of carvacrol (1) (Fig. 13.4) (Ultee et al. 2002). Removal or replacement of
the hydroxyl group with methyl ether produces lesser active compound p-cymene
(2) and methyl ether derivative of carvacrol (3) due to the lower tendency to donate
protons than the hydroxyl group (Ben Arfa et al. 2006; Marinelli et al. 2018).
Carvacryl acetate (4) is an analog of carvacrol synthesized by refluxing carvacrol,
sodium acetate, and acetic anhydride. It was then subsequently purified and characterized [Ben Arfa et al. 2006]. Carvacrol was 28 times more potent than its
structural isomer (positional isomer) thymol (5) (2-isopropyl-5-methyl phenol)
against gram-positive and gram-negative bacteria like Mycobacterium tuberculosis,
Escherichia coli, Staphylococcus aureus, and Candida albicans. Menthol (6)
(2-isopropyl-5-methyl cyclohexanol), eugenol (7) (4-allyl-2-methoxyphenyl),
vanillin (8) (4-hydroxy-3-methoxy benzaldehyde) and 3-isopropyl-5-methyl phenol
(9) were equivalent potent as compared to thymol. Replacement of isopropyl group
of menthol with vinyl group produced neo isopulegol derivative (10) [2-methyl-5(prop-1-en-2-yl) cyclohexanol], which was twice more potent antimycobacterial
agent than menthol. 4-chloro-5-isopropyl-2-methyl phenol (11) is a 4-substituted
chloro derivative of carvacrol synthesized from carvacrol exhibited similar
antimycobacterial activity as that of 2-methyl-5-(prop-1-en-2-yl) cyclohexanol (10)
(Alokam et al. 2013).
The aim of the SAR study is to develop carvacrol derivatives with potent biological activity. Patil et al. (2010) suggested carvacryl derivatives were obtained by
the attachments of acetanilide or a-chloro acetanilide group with carvacrol via ether
bonds. Comparative antimicrobial studies between carvacryl ether derivatives and
carvacrol against Bacillus subtilis, Escherichia coli, Proteus vulgaris, and
Staphylococcus aureus. The phenyl derivative of carvacryl ether (12) provided a
little antimicrobial activity against Bacillus subtulis, and inactive against other
452
A. Mondal et al.