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.