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. 2012 Feb 29;3:79. doi: 10.3389/fmicb.2012.00079

Table 1.

Chemosensitizing agents tested in combination with commercial antifungal agents against agricultural phytopathogenic and/or human mycotic fungi.

Chemosensitizer Antifungal agent Target fungus Interaction/target Reference
AGRICULTURE
Cinnamaldehyde Eugenol, quercetin, catechin Wood-decaying Synergistic/cell membrane Yen and Chang (2008)
Cinnamaldehyde Octylgallate Wood-decaying Synergistic/cell membrane Hsu et al. (2007)
Octylgallate Strobilurin, fludioxonil Penicillium expansum, Saccharomyces cerevisiae Synergistic, overcome resistance/oxidative stress Kim et al. (2010b)
2,5-dihydroxybenzoic acid Fludioxonil Aspergillus flavus Synergistic/glutathione homeostasis Kim et al. (2007b)
Berberine Fludioxonil, strobilurin A. flavus Synergistic/oxidative stress Kim et al. (2007a)
2,3-dihydroxybenzaldehyde, salicylaldehyde, other benzo analogs Strobilurin, antimycin A A. flavus, P. expansum Synergistic/HOG1 signaling pathway, oxidative/osmotic stress Kim et al. (2008b, 2011)
MEDICINE
Plant essential oils, extracts, and constituents
Carvacrol, essential oil of Origanum vulgare Azoles (theorized) Candida albicans Synergistic/ion homeostasis Rao et al. (2010)
Anethole Polygodial C. albicans Synergistic Kubo and Himejima (1991)
Anethole Amphotericin B C. albicans Antagonistic Kubo and Himejima (1991)
Anethole Miconazole, amphotericin B C. albicans Synergistic Lee and Kim (1999)
Estragole Agastache rugosa essential oil Ketoconazole Blastoschizomyces capitatus Synergistic Shin and Kang (2003)
Estragole Amphotericin B C. albicans Antagonistic Shin and Pyun (2004)
α-Pinene, 1,8-cineole, essential oil of myrtle Amphotericin B C. albicans, A. niger Synergistic Mahboubi and Ghazian Bidgoli (2010)
Essential oil Santolina chamaecyparissus/mainly terpenoids Clotrimazole C. albicans Synergistic Suresh et al. (1997)
Latex of Euphorbia characias Ketoconazole C. albicans Synergistic Giordani et al. (2001)
Essential oil of Pelargonium graveolens, mainly geraniol citronellol Amphotericin B, ketoconazole Aspergillus Additive and synergistic Shin (2003)
Essential oil of Pelargonium graveolens Nystatin C. albicans Synergistic Rosato et al. (2009)
Essential oil of Origanum vulgare Nystatin C. albicans Synergistic Rosato et al. (2009)
Essential oil of Melaleuca alternifolia Nystatin C. albicans Neutral Rosato et al. (2009)
Essential oil of Thymus vulgaris Amphotericin B C. albicans Synergistic Giordani et al. (2004)
Essential oil of Cinnamomum cassia, cinnamaldehyde Amphotericin B C. albicans Synergistic Giordani et al. (2006)
Linalool, benzyl benzoate, eugenol Fluconazole C. albicans Synergistic Zore et al. (2011)
Cinnamaldehyde analogs Fluconazole Candida Synergistic, overcome resistance/H+-efflux Shreaz et al. (2011b)
Anisaldehyde analogs Fluconazole Candida Synergistic, overcome resistance/ATPase proton pump Shreaz et al. (2011a)
Cinnamic acid Itraconazole Cryptococcus neoformans Synergistic Faria et al. (2011)
Thymol, eugenol, methyleugenol Fluconazole Candida Synergistic/ATPase proton pump Ahmad et al. (2010a,b)
Thymol, eugenol Combined together C. albicans Synergistic/plasma membrane Braga et al. (2007)
Thymol Ketoconazole, fluconazole, amphotericin B A. fumigatus, A. terreus, A. flavus Synergistic, additive, antagonistic depending upon strains/MAPK signaling pathway; oxidative/osmotic stress response Kim et al. (2008a,b)
Thymol Fluconazole, itraconazole, amphotericin B C. albicans, C. neoformans, S. cerevisiae Synergistic/drug efflux, iron uptake, ribosome biogenesis Guo et al. (2009), Bi et al. (2010), Faria et al. (2011)
Essential oil of Ocimum sanctum Fluconazole, ketoconazole Candida Synergistic/chitin synthase Amber et al. (2010)
Sesqui- and triterpenoids
Farnesol Fluconazole C. albicans, C. dubliniensis Synergistic/biofilm formation, oxidative stress, ergosterol biosynthesis Hornby et al. (2001), Oh et al. (2001), Hornby and Nickerson (2004), Jabra-Rizk et al. (2006), Shirtliff et al. (2009), Yu et al. (2012)
Retigeric acid B Fluconazole, ketoconazole, itraconazole C. albicans Synergistic/efflux pump, ergosterol biosynthesis, oxidative stress Sun et al. (2009a,b), Chang et al. (2011)
ECTA1, capisterone A and B, sulfated triterpenoids Fluconazole S. cerevisiae (overexpressing C. albicans CDR1 or MDR1) Synergistic/drug efflux Jacob et al. (2003), Li et al. (2006), Digirolamo et al. (2009)
Schinol Itraconazole, amphotericin B Paracoccidioides brasiliensis Synergistic (itraconazole), antagonistic (AMB) Johann et al. (2010)
Tea extracts, epigallocatechins, gallates (EGCG2), and polyphenols
Propylgallate Amphotericin B Candida Enhancement, synergistic/stabilization of polyenes Andrews et al. (1977), Beggs et al. (1978a,b), Beggs (1983)
l-DOPA3, dopamine Amphotericin B Candida Synergistic Andrews et al. (1979)
Propylgallate imidazoles, triazoles C. albicans Enhancement/cell membrane, ergosterol biosynthesis Strippoli et al. (2000), D’Auria et al. (2001)
Propylgallate Amphotericin B, terbinafine, butenafine, ketoconazole Fusarium and other filamentous fungi Synergistic, additive, antagonistic depending on drug and strain Xu et al. (2006)
Octylgallate Amphotericin B, fluconazole, ketoconazole A. flavus, A. fumigatus, A. terreus Synergistic/oxidative stress system Kim et al. (2010a)
EGCG Fluconazole, flucytosine Trichophyton, Candida Synergistic, overcome resistance Park et al. (2006, 2011)
EGCG Amphotericin B, fluconazole C. albicans Synergistic Hirasawa and Takada (2004)
EGCG Amphotericin B C. albicans Synergistic, prolonged survival of BALB/c mice/folic acid metabolism Navarro-Martinez et al. (2006), Han (2007a)
Grape seed extract (polyphenols) Amphotericin B C. albicans Synergistic, prolonged survival of BALB/c mice/folic acid metabolism Han (2007b)
Curcumin Fluconazole, ketoconazole, miconazole, itraconazole, voriconazole, nystatin, amphotericin B C. albicans Highly synergistic/oxidative stress system Sharma et al. (2010a,b)
Non-phenolic natural products
Diallyl trisulfide Amphotericin B C. neoformans Synergistic Shen et al. (1996)
Essential oil of Allium sativum (garlic) Ketoconazole Trichophyton Synergistic Pyun and Shin (2006)
Allicin Amphotericin B S. cerevisiae, C. albicans Synergistic/vacuolar membrane, sulfur amino acid metabolism, oxidative stress Ogita et al. (2006, 2010), Borjihan et al. (2009), Yu et al. (2010)
Allicin Fluconazole C. albicans Synergistic, in vitro and in vivo (BALB/c mice) Guo et al. (2010)
Berberine Amphotericin B Candida, C. albicans Synergistic, in vitro and in vivo (mouse) Han and Lee (2005)
Berberine Fluconazole C. albicans Synergistic Quan et al. (2006)
Berberine Strobilurin, fludioxonil, fluconazole, itraconazole A. fumigatus, C. albicans Synergistic (except itraconazole, antagonistic)/Mn-SOD Kim et al. (2007a), Xu et al. (2009), Iwasaki et al. (2010), Lei et al. (2011)
Synthetic compounds
Amiodarone Itraconazole A. fumigatus Synergistic/sodium ion transport Afeltra et al. (2004)
Amiodarone Fluconazole, itraconazole, voriconazole C. albicans Highly synergistic against resistant strains, only/Ca2+ homeostasis Guo et al. (2008), Gamarra et al. (2010)
CTBT4 Fluconazole, itraconazole S. cerevisiae pdr 3-9 mutant, C. albicans, A. niger Synergistic/oxidative stress Cernicka et al. (2007), Batova et al. (2010), Culakova et al. (2012)
Gemfibrozil, quinine, chlorpromazine Fluconazole C. albicans Synergistic Bulatova and Darwish (2008)
Ciclopirox, deferiprone Ketoconazole A. fumigatus Synergistic/iron-chelation Zarember et al. (2009)
Lactoferrin Amphotericin B A. fumigatus Synergistic/iron-chelation Zarember et al. (2009)
Triclosan Fluconazole C. albicans Synergistic Yu et al. (2011)
Geldanamycin and synthetic analogs Fluconazole A. fumigatus, A. terreus, C. albicans Synergistic/Hsp90 inhibition, PKC pathway Cowen (2009), Cowen et al. (2009), LaFayette et al. (2010), Singh et al. (2009)
Alkyl guanidine analogs Amphotericin B S. cerevisiae, C. albicans Synergistic/plasma membrane, vacuolar membrane, oxidative stress Ogita et al. (2007), Yutani et al. (2011b)
Dermaseptin S3(1–16), ranalexin Caspofungin, anidulafungin C. albicans, C. glabrata Synergistic in vitro only Harris and Coote (2010)
Porphyrin TMP-1363 and other photodynamic therapeutic agents Azole antimycotics C. albicans Synergistic/oxidative stress Chabrier-Rosello et al. (2008), Mizuno et al. (2011), Snell et al. (2011)
BHBM5 Fluconazole C. neoformans Synergistic/fungal sphingolipid pathway Dr. Maurizio Del Poeta (personal communication)

Type of interaction and target of chemosensitizer in the fungus are provided, where information is available.

19α, 11α-epoxycholest-7-ene-3β,5,6,19-tetrol 6-acetate.

2epigallocatechin gallate.

3L-β-3,4-dihydroxyphenylalanine.

47-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine.

5N′-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide.