Phytol Derivatives as Drug Resistance Reversal Agents. Issue 8 (28th May 2014)

• Record Type: Journal Article
• Authors: Upadhyay, Harish C.; Dwivedi, Gaurav R.; Roy, Sudeep; Sharma, Ashok; Darokar, Mahendra P.; Srivastava, Santosh K.
• Is Part Of: ChemMedChem. Volume 9:Issue 8(2014:Aug.)
• Page Start: 1860
• Page End: 1868
• Publication Date: 2014-05-28
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201402027
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Phytol was chemically transformed into fifteen semi‐synthetic derivatives, which were evaluated for their antibacterial and drug resistance reversal potential in combination with nalidixic acid against <italic>E. coli</italic> strains CA8000 and DH5α. The pivaloyl (<bold>4</bold>), 3, 4, 5‐trimethoxybenzoyl (<bold>9</bold>), 2, 3‐dichlorobenzoyl (<bold>10</bold>), cinnamoyl (<bold>11</bold>), and aldehyde (<bold>14</bold>) derivatives of phytol ((2<italic>E</italic>, 7<italic>R</italic>, 11<italic>R</italic>)‐3, 7, 11, 15‐tetramethyl‐2‐hexadecen‐1‐ol) were evaluated by using another antibiotic, tetracycline, against the MDREC‐KG4 clinical isolate of <italic>E. coli</italic>. Derivative <bold>4</bold> decreased the maximal inhibitory concentration (MIC) of the antibiotics by 16‐fold, while derivatives <bold>9</bold>, <bold>10</bold>, <bold>11</bold>, and <bold>14</bold> reduced MIC values of the antibiotics up to eightfold against the <italic>E. coli</italic> strains. Derivatives <bold>4</bold>, <bold>9</bold>, <bold>10</bold>, <bold>11</bold>, and <bold>14</bold> inhibited the ATP‐dependent efflux pump; this was also supported by their in silico binding affinity and down‐regulation of the efflux pump gene <italic>yojI</italic>, which encodes the multidrug ATP‐binding cassette transporter protein. This study supports the possible use of phytol derivatives in the development of cost‐effective antibacterial combinations.</p> </abstract>