Four known (1, 2, 3, and 6) and three new compounds including a 1,4-diacetyl-2,5-dibenzylpiperazine derivative (4), a quinazolinone-containing indole derivative (5), and a new ester of 2,4-dihydroxy-6-methylbenzoic acid (7) were isolated from the fungus Neosartorya pseudofischeri S. W. Peterson. Compound 2 displayed in vitro growth inhibitory activity that ranged between the activities of etoposide and carboplatin, chosen as reference compounds, in six distinct cancer cell lines. Compound 1 displayed less activity than 2. Computer-assisted phase-contrast microscopy-related analysis revealed that 2 displayed cytostatic, not cytotoxic, effects in human U373 glioblastoma and A549 non-small cell lung cancer apoptosis-resistant cells with marked inhibition of mitotic rates. Cancer cells in the remaining phases of the cell cycle were unchanged. Flow cytometry analysis further confirmed that 2 does not induce apoptotic features in U373 or A549 cancer cells. Thus, 2 represents a novel chemical scaffold from which derivatives for anticancer cytostatic compounds can be derived.
Hemileia vastatrix is the most important fungal pathogen of coffee and the causal agent of recurrent disease epidemics that have invaded nearly every coffee-growing region in the world. The development of coffee varieties resistant to H. vastatrix requires fundamental understanding of the biology of the fungus. However, the complete life cycle of H. vastatrix remains unknown and conflicting studies and interpretations exist as to whether the fungus is undergoing sexual reproduction. Here we used population genetics of H. vastatrix to infer the reproductive mode of the fungus across most of its geographic range including Central Africa, SE Asia, the Caribbean, and South and Central America. The population structure of H. vastatrix was determined using eight simple sequence repeat markers (SSRs) developed for this study. The analyses of the standardized index of association, Hardy Weinberg equilibrium, and clonal richness all strongly support asexual reproduction of H. vastatrix in all sampled areas. Similarly, a minimum spanning network tree reinforces the interpretation of clonal reproduction in the sampled H. vastatrix populations. These findings may have profound implications for resistance breeding and management programs against H. vastatrix.
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