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DNA-damaging agents are widely used in cancer therapy; however, their use is limited by dose-related toxicities, as well as the development of drug resistance. Drug discovery is essential to overcome these limitations and offer novel therapeutic options. In a previous study by our research group, pradimicin-IRD—a new polycyclic antibiotic produced by the actinobacteria Amycolatopsis sp.—displayed antimicrobial and potential anticancer activities. In the present study, cytotoxic activity was further confirmed in a panel of five colon cancer, including those with mutation in TP53 and KRAS , the most common ones observed in cancer colon patients. While all tested colon cancer cells were sensitive to pradimicin-IRD treatment with IC 50 in micromolar range, non-tumor fibroblasts were significantly less sensitive (p 1 and G 0 /G 1 phases of the cell cycle. Additionally, mass spectrometry analysis indicated that pradimicin-IRD interacted with the DNA double strand. In summary, pradimicin-IRD exhibits multiple antineoplastic activities—including DNA damage, cell cycle arrest, reduction of clonal growth and apoptosis—in the HCT 116 cell line. Furthermore, pradimicin-IRD displays a TP53-independent regulation of p21 expression in HCT 116 TP53 −/− , HT-29, SW480, and Caco-2 cells. This exploratory study identified novel targets for pradimicin-IRD and provided insights for its potential anticancer activity as a DNA-damaging agent.

Twelve chlorogenic acid derivatives and two flavones were isolated from Moquiniastrum floribundum (Asteraceae, other name: Gochnatia floribunda). Compounds were evaluated in relation to their cytotoxicity and antiradical properties. Cytotoxicity was not observed for compounds, however, chlorogenic acid derivatives showed antiradical activity and were more active than the Trolox standard. Quinic acid esterified with caffeoyl group at C-4 position showed higher antiradical activity compared to acylation at C-3 or C-5 positions. Additional caffeoyl groups esterified in quinic acid increase the antiradical activity observed for 4-caffeoylquinic acid. Excepted to 3,4-dicaffeoylquinic acid methyl ester, methyl ester derivatives show higher capacity of trapping radicals than their respective acids. Consequently, the presence of caffeoyl group at C-4 position of quinic acid is suggested as fundamental to obtain the highest antiradical activity.

We proposed a new residual to be used in linear and nonlinear beta regressions. Unlike the residuals that had already been proposed, the derivation of the new residual takes into account not only information relative to the estimation of the mean submodel but also takes into account information obtained from the precision submodel. This is an advantage of the residual we introduced. Additionally, the new residual is computationally less intensive than the weighted residual. Recall that the computation of the latter involves an n×n matrix, where n is the sample size. Obviously, that can be a problem when the sample size is very large. In contrast, our residual does not suffer from that. It can be easily computed even in large samples. Finally, our residual proved to be able to identify atypical observations as well as the weighted residual. We also propose new thresholds for residual plots and a scheme for the choice of starting values to be used in maximum likelihood point estimation in the class of nonlinear beta regression models. We report Monte Carlo simulation results on the behavior of different residuals. We also present and discuss two empirical applications; one uses the proportion of killed grasshoppers in an assay on the grasshopper Melanopus sanguinipes with the insecticide carbofuran and the synergist piperonyl butoxide, which enhances the toxicity of the insecticide, and the other uses simulated data. The results favor the new methodology we introduce.