Drugs and plant reference compounds used in this study with their PubChem IDs.

<p>Drugs and plant reference compounds used in this study with their PubChem IDs.</p

ADMET properties of potential ICL inhibitors.

<p>Abbreviations: BBB (blood-brain barrier); HIA (human intestinal absorption); Caco-2 (Caco-2 permeability); P-gp (P-glycoprotein); ROCT (renal organic cation transporter); CYP450 (cytochrome P450); CYP IP (CYP inhibitory promiscuity); HERG (human ether-a-go-go-related genes); RAT (rat acute toxicity); FT (fish toxicity); TPT (<i>Tetrahymena pyriformis</i> toxicity).</p><p>BBB, HIA, Caco-2, and aqueous solubility indicate the bioavailability of the drug in terms of absorption into the human body; P-gp, CYP450, and CYP IP indicate the metabolism, clearance, and risk of drug-drug interaction with the co-administered drug; ROCT indicates the renal excretion of the drug; HERG indicates the risk of cardiotoxicity caused by the drug; AMES toxicity indicates the risk of carcinogenicity and genotoxicity caused by the drug; RAT, LD₅₀ is the lethal dosage of drug when tested on mice; FT and TPT are the environmental risk assessments of the drug based on fish and <i>Tetrahymena pyriformis</i> as environmental indicators, respectively.</p

Alternative antifungal screening approach for <i>C. albicans</i> in YNB broth supplemented with glucose or lactate as the sole carbon source.

<p>The chart represents the averaged growth percentage with error bars of representation standard deviation. ITC is the known ICL inhibitor that served as the positive control in this experiment: it reduced the growth of <i>C. albicans</i> only in the lactate-supplemented medium. CAFF, ROS, and API caused growth reduction similar to that ITC, and hence were selected as potential ICL inhibitors for further analysis. QCT and CINN showed growth reduction in both media, which indicates non-specific inhibition or different targets. RT was the only compound that showed a glucose-specific pattern of growth reduction.</p

TCA cycle (black arrows) and glyoxylate cycle (dashed arrows).

<p>In both cycles, oxaloacetate serves as the precursor for gluconeogenesis, but the glyoxylate cycle bypasses the carbon dioxide generating steps of the TCA cycle via isocitrate lyase and malate synthase, thus conserving the carbons for gluconeogenesis. Adapted from Lorenz and Fink (2002) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095951#pone.0095951-Lorenz1" target="_blank">[9]</a>.</p

Inhibitory percentage of tested compounds in the ICL enzyme inhibition assay.

<p>The chart represents the averaged inhibitory percentage with error bars representing standard deviation. ITC is the known ICL inhibitor that served as the positive control in this experiment. CAFF, API, and ROS are the potential ICL inhibitors identified in the alternative screening experiment; they showed inhibition of ICL activity that was similar to that of ITC, with inhibitory percentage higher than 40% (in contrast to QCT, CINN, GALL, and RT).</p

Lipinski's rule-of-five drug-likeness properties of potential ICL inhibitors.

<p>Abbreviations: Mi LogP (hydrophobicity measurement: octanol/water partition coefficient); TPSA (topological polar surface area); n atoms (number of atoms); MW (molecular weight); n ON (hydrogen bond acceptor); n OHNH (number of hydrogen bond donor); n violations (number of Lipinski's rule-of-five violations); n rotb (number of rotatable bonds); MV (molecular volume).</p><p>High bioavailability are more probable for a compound when there are ≤5 hydrogen bond donors, ≤10 hydrogen bond acceptors, molecular weight ≤500, and Mi LogP ≤5; violation more than one of these rules may have problem with bioavailability <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095951#pone.0095951-Lipinski1" target="_blank">[26]</a>.</p

MIC determination of potential inhibitors of ICL1 in <i>C. albicans</i> in YNB medium.

<p>MIC determination of potential inhibitors of ICL1 in <i>C. albicans</i> in YNB medium.</p