Studies of DNA-binding properties of lafutidine as adjuvant anticancer agent to calf thymus DNA using multi-spectroscopic approaches, NMR relaxation data, molecular docking and dynamical simulation.

The interactions between lafutidine (LAF) and calf thymus DNA (ctDNA) have been investigated both experimentally and theoretically. UV-vis absorption studies confirmed that LAF binds to ctDNA through non-covalent interactions. Fluorescence quenching and time-resolved fluorescence spectroscopy studies showed that the binding of LAF with ctDNA occurred through static quenching mechanism, resulting in the formation of a LAF-ctDNA complex. The binding constants (K) of the complex were found to be around 103M-1 via NMR relaxation rates and fluorescence data, and the calculated thermodynamic parameters indicated that hydrogen bonds and van der Waals forces played major roles in the binding of LAF to ctDNA. The changes in CD spectra indicated that LAF induced a slight perturbation on the base stacking and helicity of B-DNA. A comparative study of the LAF-ctDNA complex with respect to potassium iodide quenching experiments and competition displacement assays with ethidium bromide, acridine orange, and Hoechst 33258 probes suggested that LAF interacted with ctDNA by minor groove mode. Molecular docking analysis further supported the minor groove binding. Molecular dynamics simulation indicated that LAF depart from the C-G region of DNA, but it can steadily bind with the middle part of DNA composed by A-T base pairs.

Interaction of lafutidine in binding to human serum albumin in gastric ulcer therapy: STD-NMR, WaterLOGSY-NMR, NMR relaxation times, Tr-NOESY, molecule docking, and spectroscopic studies.

In this study, lafutidine (LAF) was used as a model compound to investigate the binding mechanism between antiulcer drugs and human serum albumin (HSA) through various techniques, including STD-NMR, WaterLOGSY-NMR, (1)H NMR relaxation times, tr-NOESY, molecule docking calculation, FT-IR spectroscopy, and CD spectroscopy. The analyses of STD-NMR, which derived relative STD (%) intensities, and WaterLOGSY-NMR, determined that LAF bound to HSA. In particular, the pyridyl group of LAF was in close contact with HSA binding pocket, whereas furyl group had a secondary binding. Competitive STD-NMR and WaterLOGSY-NMR experiments, with warifarin and ibuprofen as site-selective probes, indicated that LAF preferentially bound to site II in the hydrophobic subdomains IIIA of HSA. The bound conformation of LAF at the HSA binding site was further elucidated by transferred NOE effect (tr-NOESY) experiment. Relaxation experiments provided quantitative information about the relationship between the affinity and structure of LAF. The molecule docking simulations conducted with AutoDock and the restraints derived from STD results led to three-dimensional models that were consistent with the NMR spectroscopic data. The presence of hydrophobic forces and hydrogen interactions was also determined. Additionally, FT-IR and CD spectroscopies showed that LAF induced secondary structure changes of HSA.

Influence of lafutidine combined with omeprazole in serum pepsinogen subgroup levels of patients with chronic atrophic gastritis / 中国综合临床

Objective To investigate influence of lafutidine combined with omeprazole in serum pepsinogen subgroup levels of patients with chronic atrophic gastritis. Methods One hundred and thirty-eight patients with chronic atrophic gastritis were selected in the First Affiliated Hospital of Changchun Traditional Chinese Medicine University from Dec. 2010 to Dec. 2013,who were randomly divided into two groups. Sixty-nine patients treated omeprazole( oral 1 pill/times,1 times/d)as control group,and another 69 patients were treated lafutidine( oral 2 pills/times,2 times/d ) combined with omeprazole as observation group. Both Course of treatment was 8 weeks. Changes of serum pepsinogen subgroups,improvement of clinical symptoms,treatment effect and adverse reactions were compared between two groups. Results After treatment,the levels of pepsinogen I,pepsinogen I/pepsinogen II increased significantly while pepsinogen II decreased significantly in two groups. Pepsinogen I,pepsinogen I/pepsinogen II in observation group were(89. 46 ± 13. 25)μg/L,10. 21 ± 1. 27,significantly higher than control group(( 62. 34 ± 11. 90 )μg/L,6. 45 ± 0. 93;t =7. 358,9. 125;P=0. 017,0. 004). Pepsinogen II in observation group was(8. 76 ± 3. 24)μg/L,significantly lower than control group((9. 68 ± 4. 76 )μg/L,t =4. 035,P =0. 049 ). Stomachache disappearance rate,abdominal distention disappearance rate,loss of appetite disappearance rate,total efficiency in observation group were 89. 9%, 85. 5%,84. 1% and 98. 6% respectively,significantly higher than control group( 73. 9%,65. 2%,60. 9% and 82. 6%),and the differences were statistically significant( P ﹤ 0. 05 ). Incidence of adverse reaction in observation group was 5. 8%,higher than control group( 2. 9%),but the difference was not statistically significant(χ2 =0. 697,P﹥0. 05). Conclusion Lafutidine combined with omeprazole can significantly improve clinical symptoms of patients with chronic atrophic gastritis,which can also significantly improve serum pepsinogen subgroup levels. Lafutidine combined with omeprazole have significant clinical effect and high safety, which is worthy of clinical application.