Five of the other homoisoflavanones (3–7) exhibits identical substitution patterns in ring A. Ring B of (1–7) contains either no substituent or substituents varying in hydrophobicity, electronic properties or size. The susceptibility of C. albicans to compounds (1–7) was determined and is depicted in Fig. 4. The MIC50 values suggest the potency of the synthesized compounds, whilst the Emax values suggest their efficacies. A relatively

low potency, indicated by a higher MIC50 value, suggests that higher OTX015 concentrations are needed to achieve 50% antifungal activity. Efficacy is indicative of the maximum response obtainable, with 100% suggesting that fungal growth is completely inhibited. The MIC50 and Emax values are summarized in Table 2. Compound 3 exhibited the highest potency and highest efficacy. The potency of this compound (IC50 = 25 μM) is considerably better than that of the control drug clotrimazole (IC50 = 42 μM), although the

compound could not reach 100% efficacy even at higher concentrations, suggesting fungistatic activity. Amongst compounds (4–7), compound 5 exhibited the highest efficacy, followed by compounds (6–7) with slightly lower efficacies and compound 4 with the lowest efficacy. Compound 4 also showed the lowest potency. The potencies of compounds 5 and 7 were approximately 2-fold lower than compound 6. Structural differences were investigated in order to explain the differences in efficacy and potency. Compounds Lapatinib concentration (4–7) has identical substitution patterns in ring A namely 5,7-dimethoxy substitution. The B ring of 3 is unsubstituted but compounds (4–7) are substituted respectively Carnitine palmitoyltransferase II with hydroxy, methoxy, chloride and fluoride substituents in the 4′-position of the B ring. These results suggest that the size and hydrophobicity of the substituents may play a role in the activity. Both 1 and 4 contain a 4′-hydroxy group in ring B and respectively 7,8-dimethoxy or 5,7-dimethoxy substituents in ring A. Compound 1 exhibited higher potency and efficacy than 1. This

result suggests that the 7,8-dimethoxy substitution pattern leads to reduced activity in compounds substituted with a hydroxy group in ring A. The in vitro cytotoxicity of compounds (1–7) was investigated and the IC50 values are represented in Table 3. Assessment of cytotoxicity in mammalian cells is important in the development of new drugs to ensure selectivity between species. Even if the cytotoxicity profile of a compound is not favourable, it does not prohibit its future development. Many fungal infections are superficial and topical application of drugs may reduce systemic toxicity. Compounds 3, 6 and 7 were most toxic with IC50 values between 8 and 15 μM. Compounds 1 and 5 showed slight cytotoxicity and compound 2 was not cytotoxic at the concentrations tested. All these compounds were much less cytotoxic that the reference drug emetine (0.125 μM).