Probing the origins of aromatase inhibitory activity of disubstituted coumarins via QSAR and molecular docking

This study investigated the quantitative structure-activity relationship (QSAR) of imidazole derivatives of 4,7-disubstituted coumarins as inhibitors of aromatase, a potential therapeutic protein target for the treatment of breast cancer. Herein, a series of 3,7- and 4,7-disubstituted coumarin derivatives (1-34) with R1 and R2 substituents bearing aromatase inhibitory activity were modeled as a function of molecular and quantum chemical descriptors derived from low-energy conformer geometrically optimized at B3LYP/6-31G(d) level of theory. Insights on origins of aromatase inhibitory activity was afforded by the computed set of 7 descriptors comprising of F10[N-O], Inflammat-50, Psychotic-80, H-047, BELe1, B10[C-O] and MAXDP. Such significant descriptors were used for QSAR model construction and results indicated that model 4 afforded the best statistical performance. Good predictive performance were achieved as verified from the internal (comprising the training and the leave-one-out cross-validation (LOO-CV) sets) and external sets affording the following statistical parameters: R2Tr = 0.9576 and RMSETr = 0.0958 for the training set; Q2CV = 0.9239 and RMSECV = 0.1304 for the LOO-CV set as well as Q2Ext = 0.7268 and RMSEExt = 0.2927 for the external set. Significant descriptors showed correlation with functional substituents, particularly, R1 in governing high potency as aromatase inhibitor. Molecular docking calculations suggest that key residues interacting with the coumarins were predominantly lipophilic or non-polar while a few were polar and positively-charged. Findings illuminated herein serve as the impetus that can be used to rationally guide the design of new aromatase inhibitors

Rubber plantation ageing controls soil biodiversity after land conversion from cassava

The rapid expansion of perennial crops is a major threat to biodiversity in Southeast Asia. The biodiversity losses related to the conversion of forest lands to oil palm or rubber plantations (RP) are well documented by recent studies. However, the impact of the conversion from intensively managed annual crops to perennial crops on soil biodiversity has not yet been addressed. This study aims at assessing the impact on soil biodiversity of a) the shortterm effect of land use conversion from cassava crop to RP, and b) the long-term effect of RP ageing. Soil biodiversity (bacterial, fungal and macrofaunal), microbial activities and pedoclimatic characteristics were measured over a chronosequence of 1–25 years old of RP compared to cassava fields, the former crop, in Thailand. The conversion from cassava to young RP (1–3 yr) had a significant effect on microbial biomass and activities and fungal composition, but did not impact the bacterial and macrofaunal diversity. This effect of land use conversion could be explained by the change in land management due to the cultivation of pineapple in the inter-row of the young RP. Canopy closure appeared to be the main driver of soil biota shifts, as most of the biotic parameters, composition, abundance and activities were significantly modified after 7 years of RP. The changes of composition in older rubber plantations originated from the dominance of Trichoderma (fungi), Firmicutes (bacteria), and earthworms. Old rubber plantations (23–25 yr) harboured the highest microbial and macrofaunal biomass; however, they were also characterised by a significant decrease in bacterial richness. The change in pedoclimatic conditions across the rubber chronosequence, i.e. increase in soil moisture, litter and organic carbon content, was a stronger driver of soil biota evolution than land use conversion. The macrofaunal composition was more resistant to land use conversion than the bacterial composition, whereas the microbial biomass was sensitive to land use conversion, but showed resilience after 20 years. However, bacterial, fungal and macrofaunal diversity, macrofaunal and microbial biomass and microbial activities were all sensitive to RP ageing

Accessible High-Throughput Virtual Screening Molecular Docking Software for Students and Educators

We survey low cost high-throughput virtual screening (HTVS) computer programs for instructors who wish to demonstrate molecular docking in their courses. Since HTVS programs are a useful adjunct to the time consuming and expensive wet bench experiments necessary to discover new drug therapies, the topic of molecular docking is core to the instruction of biochemistry and molecular biology. The availability of HTVS programs coupled with decreasing costs and advances in computer hardware have made computational approaches to drug discovery possible at institutional and non-profit budgets. This paper focuses on HTVS programs with graphical user interfaces (GUIs) that use either DOCK or AutoDock for the prediction of DockoMatic, PyRx, DockingServer, and MOLA since their utility has been proven by the research community, they are free or affordable, and the programs operate on a range of computer platforms