Towards new bioactive fluorine-containing 1,3,4-oxadiazole-amide derivatives: synthesis, antibacterial activity, molecular docking and molecular dynamics simulation study.

Through the approach of molecular hybridization, this study rationally designed and synthesized new trifluoromethyl-1,3,4-oxadiazole amide derivatives, denoted as 1a-1n. The findings reveal that these novel molecules exhibit potent inhibitory effects against various bacterial strains. Thereinto, compounds 1c, 1d, 1i, 1j and 1n, demonstrate relatively superior antimicrobial performance against B. cereus FM314, with a minimum inhibitory concentration (MIC) of 0.03907 µg/mL. Molecular docking analysis suggests the potential importance of the Ser57 and Thr125 amino acid residues (PDB ID: 4EI9) in contributing to the inhibitory activity against B. cereus. The consistency of these results was further corroborated through subsequent molecular dynamics simulations and MMPBSA validations. The insights gained from this study serve to facilitate the rational design and efficient development of novel eco-friendly antimicrobial inhibitors based on the trifluoromethyl-1,3,4-oxadiazole amide scaffold.

Mycorrhizal fungi alleviate acidification-induced phosphorus limitation: Evidence from a decade-long field experiment of simulated acid deposition in a tropical forest in south China.

South China has been experiencing very high rate of acid deposition and severe soil acidification in recent decades, which has been proposed to exacerbate the regional ecosystem phosphorus (P) limitation. We conducted a 10-year field experiment of simulated acid deposition to examine how acidification impacts seasonal changes of different soil P fractions in a tropical forest with highly acidic soils in south China. As expected, acid addition significantly increased occluded P pool but reduced the other more labile P pools in the dry season. In the wet season, however, acid addition did not change microbial P, soluble P and labile organic P pools. Acid addition significantly increased exchangeable Al3+ and Fe3+ and the activation of Fe oxides in both seasons. Different from the decline of microbial abundance in the dry season, acid addition increased ectomycorrhizal fungi and its ratio to arbuscular mycorrhiza fungi in the wet season, which significantly stimulated phosphomonoesterase activities and likely promoted the dissolution of occluded P. Our results suggest that, even in already highly acidic soils, the acidification-induced P limitation could be alleviated by stimulating ectomycorrhizal fungi and phosphomonoesterase activities. The differential responses and microbial controls of seasonal soil P transformation revealed here should be implemented into ecosystem biogeochemical model for predicting plant productivity under future acid deposition scenarios.

Design of novel DABO derivatives as HIV-1 RT inhibitors using molecular docking, molecular dynamics simulations and ADMET properties.

HIV-1 reverse transcriptase is an important target for developing effective anti-HIV-1 inhibitors. Different types of small molecules have been designed based on this target, showing different levels of inhibitory activity against various types of HIV-1 strains. The relationship between structure and activity of DABO derivatives was investigated by means of 3D-QSAR molecular model, molecular docking, molecular dynamics and ADMET properties. The statistical results of molecular models show that the CoMFA and CoMSIA models have good internal stability (CoMFA: q2 = 0.623, r2 = 0.946; CoMSIA: q2 = 0.668, r2 = 0.983) and external prediction ability (CoMFA: rpred2 = 0.961; CoMSIA: rpred2 = 0.961). In addition, molecular docking has explored the mechanism of action between small molecules and receptor proteins, and the results show that hydrogen bonding between amino acid Lys101 and small molecules can improve the affinity of ligands to receptor binding. A total of 12 novel molecules were designed and their activities were predicted based on the 3D-QSAR model and molecular docking results. The results showed that the designed molecules had higher predictive activity. Subsequently, 100 ns MD simulation and binding free energy verified the stability of molecular docking results. Finally, the pharmacokinetic properties of the novel designed molecule were verified by using ADMET to predict its properties. These results can provide reference for the design and development of novel and effective HIV-1 RT inhibitors, and provide new ideas for the design of subsequent drugs.Communicated by Ramaswamy H. Sarma.