In silico design of novel proton-pump inhibitors with reduced adverse effects / 医学前沿

The development of new proton-pump inhibitors (PPIs) with less adverse effects by lowering the pKa values of nitrogen atoms in pyrimidine rings has been previously suggested by our group. In this work, we proposed that new PPIs should have the following features: (1) number of ring II = number of ring I + 1; (2) preferably five, six, or seven-membered heteroatomic ring for stability; and (3) 1 < pKa1 < 4. Six molecular scaffolds based on the aforementioned criteria were constructed, and R groups were extracted from compounds in extensive data sources. A virtual molecule dataset was established, and the pKa values of specific atoms on the molecules in the dataset were calculated to select the molecules with required pKa values. Drug-likeness screening was further conducted to obtain the candidates that significantly reduced the adverse effects of long-term PPI use. This study provided insights and tools for designing targeted molecules in silico that are suitable for practical applications.

efficacy of kasmitad gel in the management of recurrent minor aphthous ulceration

To evaluate the efficacy and safety of Kasmitad [trade mark] gel for the treatment of recurrent minor aphtous ulceration, particularly when applied at the onset of prodromal symptoms. Self-controlled before - after study conducted during a 26-month period [October 2007 - September 2009]. Outpatient clinic at the School of Stomatology, Tongji University, Shanghai, China. Seventy patients with recurrent minor aphthous ulceration were randomized into the prodromal or ulceration group. Four parameters [pain score, ulcer incidence, size, duration] were recorded before and after treatment. Incidence of ulcer occurrence after treatment at different stages; changes in ulcer size, duration and pain score. Only 75.8% of subjects in the prodromal group developed an ulcer. Compared with no treatment, the maximum pain score, ulcer size, and ulcer duration were clearly reduced for subjects in both groups [p <0.01]. The two groups showed significant differences in the reduction of ulcer size and duration [p < 0.01], but no significant difference in pain scores [p= 0.236]. In the treatment of recurrent aphthous ulceration, the use of Kasmitad [trade mark] gel at the onset of prodromal symptoms can prevent progression to ulcer development and significantly reduce symptoms if ulcers do develop