Ursolic acid (UA) is a natural product which has been shown to possess a wide range of pharmacological activities, in particular those with anticancer activity. In this study, 13 novel ursolic acid derivatives were designed and synthesized in an attempt to further improve compound potency. The structures of the newly synthesized compounds were confirmed using mass spectrometry, infrared spectroscopy, and (1) H NMR. The ability of the UA derivatives to inhibit cell growth was assayed against both various tumor cell lines and a non-pathogenic cell line, HELF. Analysis of theoretical toxicity risks for all derivatives was performed using OSIRIS and indicated that the majority of compounds would present moderate to low risks. Pharmacological results indicated that the majority of the derivatives were more potent growth inhibitors than UA. In particular, 5b demonstrated IC50 values ranging from 4.09 ± 0.27 to 7.78 ± 0.43 μm against 12 different tumor cell lines. Flow cytometry analysis indicated that 5b induced G0/G1 arrest in three of these cell lines. These results were validated by structural docking studies, which confirmed that UA could bind to cyclins D1 (Cyc D1) and cyclin-dependent kinases (CDK6), the key regulators of G0/G1 transition in cell cycle, while the piperazine moiety of 5b could bind with glucokinase (GK), glucose transporter 1 (GLUT1), and ATPase, which are the main proteins involved in cancer cell metabolism. Acridine orange/ethidium bromide staining confirmed that 5b was capable of inducing apoptosis and decreasing cell viability in a dose-dependent manner.

Objective: This study aimed to evaluate the outcomes of endoscopic optic nerve decompression (EOND) for adults with traumatic optic neuropathy (TON) and seek factors that might affect surgery outcomes. Methods: From January 2016 to June 2019, 16 adults diagnosed with TON, who underwent endoscopic trans-ethmosphenoid optic canal decompression, were reviewed. All the patients were treated with steroids before the surgery. The main outcome measure was an improvement in visual acuity (VA) after treatment. Results: Eight (50.0%) patients had residual vision before the surgery, while eight (50.0%) had no light perception. After surgical decompression, partial recovery of VA was achieved in three (18.75%) patients who were operated within 10 days and had residual vision before the surgery. However, no improvement in VA was observed for the remaining patients (81.25%) who were operated more than 10 days after injuries. Conclusions: EOND is beneficial for TON not responding to steroid therapy and can prevent permanent disability if earlier intervention is done prior to irreversible damage to the nerve. Endoscopic optic nerve surgery can decompress the traumatic and edematous optic nerve with proper exposure of optic canal and orbital apex without any major complications. The operation timing and residual vision are important factors affecting outcomes.

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