Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy.
Department of Biomedical, Dental, Morphological and Functional Images Sciences, University of Messina, Messina, Italy.
PLoS One. 2019 May 2;14(5):e0216384. doi: 10.1371/journal.pone.0216384. eCollection 2019.
Drug performance in the gastrointestinal tract (GIT) plays a crucial role in determining release and absorption. In the present work, we assessed the in vitro digestion of two synthetic N1-aryl-2-arylthioacetamidobenzimidazoles (NAABs), NAAB-496 and NAAB-503, using bio-relevant models of the human stomach and small intestine. The activity of NAAB-496 and NAAB-503 against herpes simplex virus (HSV-1) replication was also investigated. NAAB-496 was resistant to pepsin in the gastric environment, with a virtual 100% recovery, which decreased to 43.2% in the small intestine. NAAB-503 was sensitive to pepsin, with 65.7% degradation after 120 min gastric phase. 1H Nuclear magnetic resonance (NMR) post in vitro digestion highlighted an alteration of NAAB-496 after the gastric phase, whereas NAAB-503 appeared comparable to the original spectral data. Both NAAB-496 and NAAB-503 revealed some antiviral activity anti-HSV-1. The 50% effective concentration (EC50) of the compounds was 0.058 mg/mL for NAAB-496 and 0.066 for NAAB-503. Future studies will evaluate the behavior of NAAB-496 within pharmaceutical formulations.
药物在胃肠道（GIT）中的表现对于释放和吸收起着至关重要的作用。在本工作中，我们使用人体胃和小肠的生物相关模型评估了两种合成的 N1-芳基-2-芳基硫代乙酰胺苯并咪唑（NAAB），即 NAAB-496 和 NAAB-503 的体外消化情况。还研究了 NAAB-496 和 NAAB-503 对单纯疱疹病毒（HSV-1）复制的抑制活性。NAAB-496 在胃环境中对胃蛋白酶具有抗药性，几乎 100%回收，而在小肠中则降低至 43.2%。NAAB-503 对胃蛋白酶敏感，胃相 120 分钟后降解 65.7%。体外消化后的 1H 核磁共振（NMR）突出显示 NAAB-496 在胃相后发生了变化，而 NAAB-503 与原始光谱数据相似。NAAB-496 和 NAAB-503 均显示出对 HSV-1 的一些抗病毒活性。两种化合物的 50%有效浓度（EC50）分别为 NAAB-496 的 0.058mg/mL 和 NAAB-503 的 0.066mg/mL。未来的研究将评估 NAAB-496 在药物制剂中的行为。
