Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure–Activity Relationship Model

The quantitative structure–activity relationship (QSAR) is one of the most popular methods for the virtual screening of new drug leads and optimization. Herein, we collected a dataset of 955 MIC values of pleuromutilin derivatives to construct a 2D-QSAR model with an accuracy of 80% and a 3D-QSAR model with a non-cross-validated correlation coefficient (r2) of 0.9836 and a cross-validated correlation coefficient (q2) of 0.7986. Based on the obtained QSAR models, we designed and synthesized pleuromutilin compounds 1 and 2 with thiol-functionalized side chains. Compound 1 displayed the highest antimicrobial activity against both Staphylococcus aureus ATCC 29213 (S. aureus) and Methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentrations (MICs) < 0.0625 μg/mL. These experimental results confirmed that the 2D and 3D-QSAR models displayed a high accuracy of the prediction function for the discovery of lead compounds from pleuromutilin derivatives

Genetic Analysis of Fruit Traits in Wolfberry (<i>Lycium</i> L.) by the Major Gene Plus Polygene Model

The fruit diameter (FD), fruit length (FL), fruit peduncle length (FPL), fruit weight (FW) and fruit index (FI, FL/FD) are important quantitative traits in wolfberry fruit, and also one of the most important goals of variety breeding; however, the inheritance of these traits has not been studied to date. In this study, the genetic analysis of these five fruit traits was undertaken for four pairs of F1 hybrid populations (CI, CII, CIII and CIV) using the major gene and polygene mixed inheritance model. The results showed that the five fruit traits exhibited super-parent segregation in four hybrid combinations, and five traits of progeny with abundant genetic diversity. In CII, CIII and CIV, the mid-parental heterosis ratio (RHm%) of FD, FL, FPL and FI was greater than 0 with positive heterosis. FD, FL and FI in CI, CII and CIII were controlled by one pair of additive-dominant major genes (A-1). However, in CIV, FD was controlled by two pairs of additive-dominant alleles (B-6) and FL was best fitted to polygenic control (A-0). In addition, it was found that FPL in CI, CIII and CIV was controlled by one or two pairs of additive-dominant major genes (A-1, B-6, B-1), and FW in CIII and CIV was also controlled by one or two pairs of additive-dominant major gene controls (A-1, B-1). For FD, FPL, FW and FI in CIII and FPL and FW in CII, the major genes heritability was over 50%, indicating that these traits are affected by both genes and the environment, and that the selection of these traits should be considered in later generations due to the large effect of environmental factors. Therefore, this study provides a theoretical basis for QTL mapping and early selection of hybrid breeding of Lycium fruits