Small molecule kinase inhibitors (SMKIs) are of heightened interest in the field of drug research and development. There are 79 (as of July 2023) small molecule kinase inhibitors that have been approved by the FDA and hundreds of kinase inhibitor candidates in clinical trials that have shed light on the treatment of some major diseases. As an important strategy in drug design, computer-aided drug design (CADD) plays an indispensable role in the discovery of SMKIs. CADD methods such as docking, molecular dynamic, quantum mechanics/molecular mechanics, pharmacophore, virtual screening, and quantitative structure–activity relationship have been applied to the design and optimization of small molecule kinase inhibitors. In this review, we provide an overview of recent advances in CADD and SMKIs and the application of CADD in the discovery of SMKIs.

Pathogenic plant oomycetes cause devastating damage to fruits and vegetables worldwide. Plant essential oils (EOs) are known to be promising candidates for the development of fungicides. In this study, we isolated twelve EOs from Tetradium ruticarpum, Tetradium daniellii, Tetradium fraxinifolium, Zanthoxylum armatum, Ruta graveolens, and Citrus medica leaves and fruits. We then investigated their chemical composition and antifungal activity against phytopathogenic oomycetes. Our results demonstrated that Z. armatum fruit essential oil (ZFO) in particular substantially inhibited the mycelial growth of Phytophthora capsici. Similarly, ZFO also strongly suppressed spore production and germination of P. capsici, and the application of ZFO significantly reduced disease symptoms caused by P. capsici in pepper. Furthermore, results from microscopic and biochemical studies indicated that ZFO damaged the ultrastructure and destroyed the membrane integrity of P. capsici, leading to the leakage of the cellular contents and ultimately causing cell death. It was concluded that ZFO could enhance the activities of defense-related enzymes in pepper fruits, which may also be responsible for the inhibition of phytophthora disease. Moreover, linalool and D-limonene were proven to be the primary effective components of ZFO. Our results collectively indicate that ZFO could be a potential candidate for the management of disease caused by P. capsici.

Two novel lathyrane-type diterpenoids, which possess atrans-gem-dimethylcyclopropane were obtained from seeds ofEuphorbia lathyris. TheEuphorbiafactor L_2bexhibited an inhibitory effect against U937 cell line with an IC₅₀value of 0.87 μM.

Rational engineering of native β-CD as an ideal chiral selector for a definite analyte in capillary electrophoresis represents a challenge in separation science. Herein, a rational and systematic strategy that combines the de novo design and molecular modeling is firstly described to expedite the manipulation and selection of effective selector for enantioseparation in capillary electrophoresis. Using β-adrenoreceptor agonists as model analytes, we demonstrate how this strategy efficiently improves the enantiorecognition in chiral discrimination sites of inclusion complexes. The evolved β-CD derivative could be utilized as a chiral receptor to achieve the effective enantioseparation (R_s > 1.5) of racemic β-adrenoreceptor agonists. We highlight a novel strategy for efficiently and rapidly manipulating native CD based on the characteristics of analyte so as to gain an excellent chiral selector.

Phytophthora capsici is a highly destructive phytopathogenic oomycete with a broad host range and is responsible for tremendous losses. Euphorbia factor L₃ (EFL₃) is a natural plant-derived compound that has been widely studied in medicine and cosmetic applications. In this study, the sensitivity of 105 P. capsici isolates to EFL₃ was determined, and the biological activity and physiological effects of EFL₃ against P. capsici were investigated. The median effective concentration (EC₅₀) values for EFL₃ inhibition mycelial growth and spore germination ranged from 0.66 to 8.94 μg/mL (mean, 2.96 ± 0.91 μg/mL) and 1.63 to 13.16 μg/mL (mean, 5.30 ± 1.64 μg/mL), respectively. EFL₃ treatment resulted in cell wall and cell membrane damage of P. capsici, which was revealed by morphological and ultrastructural observations, propidium iodide (PI) and calcofluor white (CFW) staining, and measurements of relative conductivity as well as malondialdehyde (MDA) and glycerol contents. In addition, the contents of phospholipid and cellulose, which are the major components of cell membrane and cell wall, were significantly reduced following EFL₃ treatment. Furthermore, EFL₃ provided protective as well as curative efficacies against P. capsici on detached tomato leaves and pepper seedlings in vivo. These data show that EFL₃ exhibits strong inhibitory activity against P. capsici, thereby suggesting that it could be an effective alternative for controlling P. capsici-induced diseases.