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HIV-1 integrase (IN) is an essential enzyme for retroviral replication. There is no analogue for this enzyme in human cells so that inhibition of IN will not bring strong effect on human body. Thus, HIV-1 IN has become a rational target for therapy of AIDS. This review provides a comprehensive report of alpha, gamma-diketo IN inhibitors discovered in recent years. Compilation of such data will prove to be beneficial in developing QSAR, pharmacophore hypothesis generation and validation, virtual screening and synthesis of compounds with higher activity.

Effects of osthole (Ost) and verapamil (Ver) were investigated in the isolated guinea-pig ileum and taeniae coli. In the isolated guinea-pig ileum or taeniae coli, Ost and Ver were both found to inhibit the contractions induced by acetylcholine (ACh), histamine (His) and KCl in a dose-dependent manner; and noncompetitively antagonize the CaCl2 cumulative dose-response curves, with pD2 values of 4.41 +/- 0.15 and 7.0 +/- 0.2, respectively. Ost at dose of 100 mumol/L and Ver at 1 mumol/L inhibited CaCl2 0.2 mmol/L induced the contractions of the isolated guinea-pig taeniae coli, and the contractions can be abolished by adding CaCl2 2 mmol/L in Ca(2+)-free medium; both of them showed pronounced inhibitions on intracellular calcium-dependent contractions induced by ACh, but showing no effects on the extracellular calcium-dependent contractions. These results indicate that Ost has calcium antagonistic effect and is similar to Ver in mechanism.

On isolated isthmus of oviduct of the rabbit, Isocorydine (Isoc) (3 mu mol/L) decreased significantly the frequency of spontaneous contraction and muscle tension, but not the amplitude of contraction. The tension and frequency of spontaneous contraction can be suppressed by Isoc at concentrations from 3 to 300 mumol/L. The amplitude of contraction was decreased only at 300 mu mol/L. It is suggested that the frequency and tension of spontaneous contraction of isthmic muscle are more sensitive to Isoc than the amplitude. Isoc antagonized the norepinephrine-induced contraction of the oviduct. The transport of ova through the oviduct reduced by hCG could be delayed by Isoc.

The effects of dicarboxyethenylgermanium sesquioxide (DCG) on electrical and mechanical activity in isolated guinea pig papillary muscles and rabbit sinus node were studied by intracellular capillary glass electrode. The effects of DCG on slow action potential and contractile force (Fc) of preparations in which the fast Na+ channels were inactive by partial depolarization by increasing the concentration of K+ 25.4 mmol/L were observed. DCG (0.5 mol/L) increased Vmax and APA of fast action potential of guinea pig papillary muscles, but its Fc decreased from 105 +/- 12% of control to 80 +/- 16%. DCG prolonged the spontaneous cycle length (SCL) and APD90 of rabbit sinus node, but the slope of phase 4(SP4) was lowered. The functional refractory period (FRP) of rabbit left atria was determined by the paired stimulus method. In experiments involving one drug, the drug was added until equilibrium had been reached. It has been demonstrated by experiments that the administration of DCG resulted in an increase of atrial FRP. These findings suggest that the Ca2+ inward currents and the K+ outward current may be inhibited by DCG.