X-ray, structural assignment and molecular docking study of dihydrogeodin from <i>Aspergillus Terreus</i> TM8

<p>A re-cultivation of the thermophilic fungus <i>Aspergillus terreus</i> TM8, and working up of its extract afforded the dichloro-benzophenone derivative, dihydrogeodin (<b>1</b>) in addition to the butyrolactones I (<b>2</b>), V (<b>3</b>) and VI (<b>4</b>). A literature surveying revealed one recent structural assignment trial for dihydrogeodin (<b>1</b>), however, with some inaccuracies. We report herein a full assignment of dihydrogeodin (<b>1</b>) using extensive study of 1D, 2D NMR and ESI HR mass data. For the first time as well, we report the planar structure of <b>1</b> using X-ray crystallography. Docking and molecular dynamic simulation of dihydrogeodin (<b>1</b>) on the isomerase cyclophilin A has revealed its significant potential activity as an antiviral and immunosuppressive agent.</p

X-ray, structural assignment and molecular docking study of dihydrogeodin from <i>Aspergillus Terreus</i> TM8

<p>A re-cultivation of the thermophilic fungus <i>Aspergillus terreus</i> TM8, and working up of its extract afforded the dichloro-benzophenone derivative, dihydrogeodin (<b>1</b>) in addition to the butyrolactones I (<b>2</b>), V (<b>3</b>) and VI (<b>4</b>). A literature surveying revealed one recent structural assignment trial for dihydrogeodin (<b>1</b>), however, with some inaccuracies. We report herein a full assignment of dihydrogeodin (<b>1</b>) using extensive study of 1D, 2D NMR and ESI HR mass data. For the first time as well, we report the planar structure of <b>1</b> using X-ray crystallography. Docking and molecular dynamic simulation of dihydrogeodin (<b>1</b>) on the isomerase cyclophilin A has revealed its significant potential activity as an antiviral and immunosuppressive agent.</p

PSA and Gleason sum scores of SCT population.

<p>(a) Dot blot showing the pre and post-SCT nadir PSA for the entire patient cohort, (b) Bar chart representing the numbers of patients with different Gleason sum scores prior to SCT.</p

Post-SCT complications and the number of patients affected by each complication.

<p>Post-SCT complications and the number of patients affected by each complication.</p

Summary demographics of our series of patients who received SCT.

<p>Breakdown of patient demographics and tumour parameters from the three cryotherapy centres can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069243#pone.0069243.s004" target="_blank">Table S1</a>. Please note that not all categories add up to 283, since data was incomplete for some patients as regards Pre Rx Gleason, Pre Rx PSA and Clinical T score. (Rx  =  cryotherapy).</p

Simplified analysis of gland length and the largest iceball dimension against IPSS scores.

<p>Significant association between gland length and iceball length with (mean and maximal) IPSS scores were observed. (1_C and 2_C denotes 1^st and 2^nd cycles, respectively; n  =  patient numbers).</p

Disease free survival by (a) Pre-SCT PSA, (b) Gleason Score and (c) PSA nadir.

<p>Disease free survival by (a) Pre-SCT PSA, (b) Gleason Score and (c) PSA nadir.</p

Summary of multivariate analysis.

<p>Multivariate analysis of SCT parameters reveals highly significant association between dimensions of gland length and the iceball with patients' IPSS scores. (1_C and 2_C denotes 1^st and 2^nd cycles, respectively; Right and left lobe signified the nadir temperature recorded below 0°C; Iceball Length signifies the dimension of iceball parallel to the anterior rectal wall, measured in mm, at the end of each freeze cycle; n  =  patient numbers).</p

Association between gland length and maximal length of iceball recorded with patient IPSS outcome.

<p>(Max Lobe represents the lowest temperature below 0°C recorded in the prostate; Max Iceball is taken as the longest dimension of iceball recorded for the entire procedure; n  =  patient numbers.).</p

A five month follow up of an efficacy study for a <i>T. evansi</i> experimentally infected goat model, using the haematocrit centrifugation technique (HCT), after treatment with Diminazene, DB 75, DB 867 or DB 1192 at various compound doses.

<p>The results are depicted as negative (−) or positive (+) for motile trypanosomes observed in goat blood samples, along with goats, which died (<i>D</i>) or were removed from the project (<i>Rem</i>) during the study period.</p