3,6,9,12,15,18,21,24,27-Nonaoxatriacont-29-yn-1-ol

A Schiff base of gossypol with 3,6,9,12,15,18,21,24-octaoxa-pentacosylamine (GSOB) forms stable complexes with monovalent cations. This process of complex formation was studied by electrospray ionization-mass spectrometry, (1)H-NMR and Fourier transform infrared spectroscopy as well as by the PM5 semiempirical method. It was found that GSOB forms 1:6 complexes with Li(+) and Na(+), and 1:4 complexes with K(+) as well as 1:2 complexes with Rb(+) or Cs(+) cations and exists in all these complexes in the enamine-enamine tautomeric form. Moreover, within these complexes only Li(+) cations can fluctuate between the oxygen atoms of the octaoxaalkyl chains. The interactions of Li(+) cations with hydroxyl groups of the gossypol part is also possible. All other cations are much more localized. In the complex of GSOB with protons, a 1:2 stoichiometry is realized. The two protons are localized on the N atoms of the Schiff base, and the complex exists in the imine-imine tautomeric form. The structures of the complexes are calculated by PM5 semiempirical methods and discussed.

Purpose:To determine whether emixustat hydrochloride (emixustat) reduces the rate of enlargement of geographic atrophy (GA) compared with placebo in subjects with age-related macular degeneration (AMD) and to evaluate the safety and tolerability of emixustat over 24 months of treatment.Design:Multicenter, randomized, double-masked, placebo-controlled, phase 2b/3 clinical trial.Participants:Patients with GA secondary to AMD, a visual acuity score of at least 35 letters, and GA with a total area of 1.25 to 18 mm2 were enrolled. Methods:Subjects were randomized (1:1:1:1) to emixustat 2.5 mg, 5 mg, 10 mg, or placebo, administered orally once daily for 24 months. Visits included screening, baseline, and months 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, and 25.Main outcome measures:The primary efficacy end point was the mean annual growth rate of total GA area in the study eye, as measured by a central reading center using fundus autofluorescence (FAF) images. The change from baseline in normal luminance best-corrected visual acuity (NL-BCVA) was a secondary efficacy end point. Results:Of 508 randomized subjects, 320 completed the study. Demographics and baseline characteristics were comparable between treatment groups. On average, GA lesions in the study eye grew at a similar rate in each group (emixustat: 1.69 to 1.84 mm2/year; placebo: 1.69 mm2/year; P ≥ 0.81). Changes in NL-BCVA were also comparable between groups. Subjects with a larger low luminance deficit (LLD) at baseline (≥20 letters) demonstrated a more rapid growth of GA over 24 months. No relationship was observed between the risk-allele status of the AMD-associated single-nucleotide polymorphisms tested and the growth rate of GA. The most common adverse events in emixustat-treated subjects were delayed dark adaptation (55%), chromatopsia (18%), visual impairment (15%), and erythropsia (15%).Conclusions:Emixustat did not reduce the growth rate of GA in AMD. The most common adverse events were ocular in nature and likely related to the drug's mechanism of action. Data gained from this study over a 2-year period add to the understanding of the natural history of GA and the baseline characteristics affecting the growth rate of GA.

Even though existing remote-sensing-based drought indices are widely used in many different types of ecosystems, their utility has not been widely assessed in tropical dry forests (TDFs). The aim of this study is to evaluate the performance of three remote-sensing-based drought indices, the Vegetation Condition Index (VCI), Temperature Condition Index (TCI), and Vegetation Health Index (VHI), for meteorological drought monitoring in TDFs using the moderate-resolution imaging spectroradiometer (MODIS) products. The correlation between the VCI, TCI, and VHI and multiple time scales of the Standardized Precipitation Index (SPI) (1, 3, 6, 9, 12, 15, 18, 21, 24 months) for each month (January to December) and each season (dry season, dry-to-wet season, wet season and wet-to-dry season) were conducted using the Pearson correlation analysis. We also correlated year-to-year changes of satellite-based drought indices with the changes of the in situ annual SPI (A_SPI) which provides annual information on the mean meteorological drought. The analysis reveals that the ability of these remote-sensing-based drought indices for meteorological drought monitoring varies with timing, and the TCI outperforms the VCI and VHI in terms of seasonal and annual scale. These remote-sensing indices performed well in monitoring meteorological drought in the dry season, poorly in the in the dry-to-wet season, and moderately in the wet season. The TCI performed best in monitoring meteorological drought in the wet-to-dry period, followed by VHI, whereas the VCI performed worst. All of these remote-sensing-based drought indices failed to detect drought in May during the green-up period and in September, October, and November when the water content in the root regions was abundant. Our results indicate that the evapotranspiration of TDFs is more sensitive than canopy greenness to detect meteorological drought. Results from this study increase the ability to provide real-time drought monitoring and early warnings of drought in TDFs.