Journal of Chinese Pharmaceutical Sciences

Quantum Chemistry and QSAR Studies of Optical Isomers of 3-Methylfentanyl and Ohmefentanyl

Hong-Wu Wang, Zhi-Xian Wang, Kai-Xian Chen, Ru-Yun Ji

1996, 5(3): 113-120.

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The analgesic activities of four 3-methylfentanyl and eight ohmefentanyl optical isomers are very different. In seeking for the reason why a small change in structure leads to such a great difference in activity, we carried out quantum chemistry and QSAR investigations on these compounds. It was found that the spatial relationship between 3-methyl group and the anilidophenyl was most important. Other factors such as the net atomic charge on carbonyl oxygen and the configuration of 1-(-hydroxy also influenced the activities. PLS method was used for the construction of QSAR model. Using only 3 latent variables the correlation and predictive ability were quite satisfactory.

3D-QSAR Studies on Retioids of Anticarcinogenic Activiy

Niu Huang, Min-Min Wang, Feng-Ming Chu, Zong-Ru Guo^*

1996, 5(3): 121-127.

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Using comparative molecular field analysis (CoMFA), a 3D-QSAR model of anticarcinogenicity (inhibiting the induction of ODC) for a series of retinoids was established. The CoMFA model was validated and built by cross-validation (leave-one-out)and non-validation (randomizing) techniques. The significant PLS cross-validated value (Rcv² = 0.905)indicated that the model could be used as a predictive tool for further design of new molecules with high activity. The activities of three compounds excluded from the correlation analysis were computed using this model, small residues obtained. Based on the conformers with the lowest energy, no statistical significance existed (Rcv² = 0.405). A performance of minor rotation around a single bond for several compounds provided the conformers with the variation in energy limit less than 2 kcal/mol, by which a correlation analysis was run with a satisfactory relationship between the perturbed conformers and the activities, suggesting that the lowest energy conformers for some compounds be unlikely the pharmacophoric conformers. Superimposition of ligand fields was carried out to mimic the environment of ligands interacting with their receptor, and to visualize the steric and electrostatic behaviors of groups and/or atoms between ligands and receptor. The molecular field model as a template is able to predict activities, and to some extent, to map the topological and physic-chemical characteristics of receptor.

A New Saikosaponin from Bupleurum scorzonerifolium

Li Tan, Yu-Ying Zhao, Ru-Yi Zhang, Shao-Ling Hong

1996, 5(3): 128-131.

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A new saikosaponin was isolated from the roots of Bupleurum scorzonerifolium Willd. and its structure was elucidated on the basis of spectral analysis. It was identified as 3β, 16α, 23, 28, 30-pentahydroxy-olean-11, 13(18)-dien-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→3)-β-D-fucopyranoside and named as saikosaponin r.

Studies on the Anti-lipid Peroxidative Actions of the Methanolic Extract of the Root of Aegle marmelos and Its Constituents In Vivo and In Vitro

Xiu-Wei Yang, Masao Hattori, Tsuneo Namba

1996, 5(3): 132-140.

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The inhibitory effect of the methanolic extract of the root of Aegle marmelos (MERA) and its constituents on the lipid peroxidation in vivo and in vitro were studied. The results suggested that MERA increased the activities of superoxide dismutase (SOD) and GSH-peroxidase in the liver cytosol of mice, but showed no significant effect on the activity of catalase, and one of its major constituents, 4-methoxy-1-methyl-2-quinolone (MMQ) increased the activity of SOD in liver tissue of mice intoxicated with FeCl2-ascorbic acid (AA)-ADP in vivo. Various constituents isolated from the root of title plant inhibited the lipid peroxidation in rat liver homogenate, which was in vitro induced by FeCl2-ascorbic acid, CCl4-NADPH, or ADP-NADPH. Of the test compounds, MMQ and its derivatives integriquinolone were similar to (-tocopherol in inhibiting MDA production in rat liver microsomes induced by Fe²⁺-ascorbate, CCl4-NADPH, or ADP-NADPH.

Studies of Site Specific DNA Binding of Small Peptides by Competitive Assays with Hoechst 33258

Ming Yang, Shu-Mei Zhu, Yan-Ping Huang, Qi-Yue Hu, Kui Wang

1996, 5(3): 141-146.

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With a view to finding out precisely how small peptides recognize a particular binding site of DNA, we have accomplished DNA binding studies of two peptides, H-Tyr-Arg-OH (YR) and H-Gly-Gly-His-OH (GGH) by using measurements in comparison with the binding between DNA and Hoechst 33258. The inhibition mode by YR and GGH to DNA binding of Hoechst 33258 was analyzed by Lineweaver-Burk plot which shows the plot of typical competitive inhibition at concentration of Hoechst 33258 from 3.66 (10^-9 mol/L to 1.09 ( 10^-8 mol/L. And it is concluded that YR binds to DNA in its minor groove (AT rich regions) with a binding constant K = 1.02 ( 108 (mol/L)^-1. The GGH (s specificity is reduced at high concentration because it can also bind GC base pair.

Pharmacokinetics and Absolute Bioavailability of the Sublingual Naloxone Hydrochloride Tablet in Dogs

Zhao-Heng Ge, Hua Li, Ning Wang, Jin-Du Liang

1996, 5(3): 147-149.

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The pharmacokinetics and absolute bioavailability of the sublingual naloxone tablet were studied with HPLC-electrochemical detection. Eight male dogs received single 5 mg dose of naloxone intravenously, the plasma concentration-time curves could be fitted to two-compartment open model, with 12.0 min of t1/2α, 143.4 min of t1/2β and 7.92 mg·min/L of AUC. The same eight dogs received 5 mg dose of the sublingual naloxone tablet after an interval of a week. The main pharmacokinetic parameters were: t1/2ka = 11.0 min, t1/2α = 15.4 min, t1/2β = 164.1 min, Tmax = 27.7 min, Cmax = 34.2 ng/ml, and AUC = 6.79 mg·min/L, respectively. The plasma concentration-time curves were fitted to the first order absorption two-compartment open model also. The mean absolute bioavailability of the sublingual naloxone tablet was 86.8(10.9%. No statistically significant differences were found with t1/2α, t1/2β, and between the two routes of administration. These results indicated that the course of disposition for naloxone in dogs was similar for the two routes of administration, and the absolute bioavailability of the sublingual naloxone tablet was high. Thus satisfactory clinical effects could be expected.

Protection of Calcitonin Gene-Related Peptide-Induced Preconditioning against Myocardial Injury due to Adriamycin in the Isolated Rat Heart

Dong-Liang Yang, Yu-Hai Tang, Yuan-Jian Li, Chang-Fu Peng, Xiao-Ming Xiong

1996, 5(3): 150-153.

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The protective effect of calcitonin gene-related peptide (CGRP)-induced preconditioning on myocardial injury due to adriamycin was studied in the isolated perfused rat heart. Adriamycin (100 and 200 (mol/L) caused a gradual decrease in coronary flow (CF) and cardiac function (LVP and LV dp/dtmax), and an increase in the level of MDA. Pretreatment with CGRP at the concentration of 5 nmol/L for 5 min markedly reduced the attenuation of CF and cardiac function and inhibited the elevation of MDA content induced by adriamycin. The findings suggest that the pretreatment with CGRP possesses a protection against myocardial injury elicited by adriamycin. The present results also suggest that the protection of CGRP may be related to a reduction in lipid peroxidation.

Effect of Fish Oil on β-Adrenoceptors and the Activity of Adenylate Cyclase on Myocardial Membrane in Rats

Jian-Zheng Zhou^*, Bao-Jie Wu, Xiu-Mei Zhang

1996, 5(3): 154-159.

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Effects of fish oil on β-adrenoceptors as well as the activity of adenylate cyclase (AC) on rat myocardial membrane were investigated.Supplementation with fish oil had no significant effect on basal activity of AC on myocardial membrane whereas it could markedly inhibit the AC activity stimulated by isoproterenol (ISO). Radioligand binding assays showed that supplementation with fish oil had no effect on Bmax and Kd, compared with saline control. However, supplementation with sheep oil could markedly reduce both the Kd and Bmax, compared with saline control. And the Kd of sheep oil group was greatly decreased than that of fish oil group. The results suggested that supplementation with fish oil mainly affected the activation of AC, not β-adrenoceptor itself.

Synthesis of Germanium Propionyl Amino Acid Esters Sesquioxides

Guo-Xiang Liu, Wen-Xiang Hu^*, De-Rong Hu, Xin-Wei Zhang, Liu-Hong Yun

1996, 5(3): 160-164.

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The Study on Interaction of Platinum (Ⅱ) Complexes with G-actin and Transmembrane Transport of Platinum (Ⅱ) Complexes by Human Erythrocytes

Juan Zou, Kui Wang

1996, 5(3): 165-167.

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