In order to develop new taxol analogues with possible antitumor properties, sinenxan A (SIA), a new biosynthetic taxoid, was chemically modified, mainly by esterification of C14-OH with taxol-like side-chain acids. Twenty-one new taxoids thus formed were tested on three kinds of cell lines. Their activities are far below those of taxol. The SAR of SIA derivatives partly agree with that of taxol and can be roughly discerned.

Howiinol(GHM-10) is a new compound isolated from Goniothalamus howii. Previous studies showed that GHM-10 significantly inhibited the growth of cancer cells both in vitro and in vivo. In the present study, the characteristics of the inhibitory effect of GHM-10 on L1210 cells was investigated. The results showed that the IC50 of L1210 cells treated with GHM-10 for 1 h, 24 h, and 7 d was 6.85, 3.32 and 1.59 micrograms.ml-1, respectively. This outcome is in compliance with the hypothesis that GHM-10 is a cell cycle non-specific cytotoxic drug. When L1210 cells were treated with 1-2 micrograms.ml-1 of GHM-10 for 24 h, the growth rate and mitotic index were decreased and the morphology of cell nuclei changed, but the cell viability remained at the level of 96% or more, indicating that GHM-10 mainly inhibited cell proliferation. The cell cycle kinetics of L1210 cells were studied by using a flow cytometer. The results showed that the transition of cells from G1 phase to S phase was blocked to certain extent by the treatment of GHM-10 4 micrograms.ml-1 for 12 h. The fluidity of cell membrane was also increased when the L1210 cells were exposed to 2-3 micrograms.ml-1 of GHM-10 for 24 h.

Howiinol A(1), one of the active antitumor constituents from the root and stem bark of Goniothamus howii Meer. (Annonaceae) has been synthesized in nine steps from alpha-D-glucoheptonic gamma-lactone with an over all yield of 13.3%. It shows that all data of the synthetic product are identical to those of the natural howiinol A, thus the absolute configuration of natural howiinol A is further confirmed as 1. In the search for new antitumor compounds with high potency, 26 analogues have been synthesized. In pharmacological tests most of them showed antitumor activities in vitro, some of them are significant.

Sinenxan A is a new biosynthetic taxane. In order to search for new taxol analogues with cytotoxicity, sinenxan A was modified and studied. Ten new taxoids containing the tetrahydrofuran ring were esterified at C14 or C10 positions with taxol/taxotere side chain. Preliminary pharmacological tests showed that some of the compounds have certain cytotoxicity on KB, HCT-8 and A2780. Meanwhile, the relationship between their structures and activity was discussed.

The antitumor constituents were isolated from Pteris semipinnata L. (PsL), a Chinese traditional herb, and screened using tetrazolium salt (MTT) method. Their cytotoxic effects in vitro on several human tumor cell lines were studied. Compounds 5F, 6F, A and the ethanolic extract of PsL (PSE) were shown to have strong cytotoxicity against five cell lines: human liver adenocarcinoma cell line (HePG II), human lung adenocarcinom a cell line (SPC-A-1), human gastric adenocarcinoma cell line (MGC-803), human nasopharyngeal carcinoma cells in low differentiation (CNE-2Z) and human liver adenocarcinoma cell line (BEL-7402) in different degrees in a dose-dependent manner; compound 6F was the most active one, whose IC50 after 72 h treatment for the above five cell lines were 0.343 +/- 0.003, 0.115 +/- 0.022, 0.590 +/- 0.032, 0.328 +/- 0.066 and 0.221 +/- 0.058 microgram.ml-1, respectively. Compounds A and 5F were less active; no cytotoxicity of compounds 4F and B were detected on the five cell lines. Analysis of the relationship between structure and activity revealed that the antitumor activity portion in the structure is the alpha, beta-methylene cyclopentanone moiety, and the site and number of the hydroxy groups affect the cytotoxicity of these agents significantly.

A novel spin labeled analogue of podophyllotoxin glycoside 9 was synthesized by condensing 4'-demthyl-epipodophyllotoxin-beta-D-glucopyranose and 4-formyl-2, 2, 6, 6-tetrahydropuridine in presence of p-TsOH and triethyl orthoformate. It was shown to exhibit activity compatible to VP-16-213 in inhibiting L1210 cells.

The absorbance, fluorescence and cyclic voltammetric methods as well as agarose gel electrophoresis were used to study the interaction of the antitumor compound Et2SnCl2(phen) with DNA. The results indicate that Et2SnCl2 (phen) mainly reacts electrostatically with the phosphate backbone of DNA. There also exists an intercalation into the double-helix of DNA through the phenanthroline group of Et2SnCl2(phen). At high concentration Et2SnCl2(phen) can cause unwinding of DNA. The molecular action mechanism of Et2SnCl2(phen) with DNA was first proposed.

In order to develop new generation of taxol-like anticancer agents with fewer side effects, improved activity, superior pharmacological properties and broad antitumor spectrum, along with structure-activity relationship study, a series of new taxol derivatives are to be synthesized starting from sinenxan A--a biosynthetic taxane. Eight new 14 beta-side chain taxol derivatives with 4-OH and 4-Ac were synthesized in 5 and 6 steps from semisynthetic taxoid intermediate 7, respectively. These included taxol derivatives modified at C-2 position with benzoate, m-Cl benzoate, valerate and phenylacetate. All target compounds together with two other 14 beta-side chain taxol derivatives were tested in a microtubule assembly assay, and in an in vitro cytotoxicity assay (KB, A2780, HCT-8 cell line). All compounds had no effect in the microtubule assembly assay at 10 mumol.L-1. Most of them showed marginal activity in the in vitro cytotoxicity. The structure-activity relationship was different from taxol derivatives. 2-Aliphatic ester displayed similar activity to 2-aromatic ester, which indicated that the aromatic group at C-2 position was not important for cytotoxicity. Comparing among themselves, 4-OH derivatives possessed stronger activity than 4-Ac.

Howiinol(GHM-10), a new compound isolated from Goniothalamus howii, had been shown to have marked anticancer activity both in vitro and in vivo. In the present study, the effect of GHM-10 on the biosynthesis of macromolecules in L1210 cells was investigated. By using [3H] labeled precursor incorporation assays, we found that the biosyntheses, of DNA, RNA and protein in L1210 cells were inhibited markedly after the cells were pretreated with GHM-10 in 4-12 micrograms.ml-1 for 6 h and the inhibition of DNA synthesis was the most obvious one. We also used the methods of [3H]TdR incorporation curve, shift of UV-absorption spectrum and shift of fluorescence spectrum to investigate the mechanism of inhibitory action of GHM-10 on DNA biosynthesis. The results showed that the inhibition of DNA synthesis already became irreversible after the L1210 cells were treated with GHM-10 in 6-8 micrograms.ml-1 for 1 h, indicating that GHM-10 may induce damage on DNA molecular structure. However, when calf thymus DNA was treated with GHM-10, the UV-absorption spectrum and the fluorescence spectrum of the DNA were not changed significantly. It is suggested that GHM-10 was not able to intercalate into DNA molecules or to damage the structure of DNA directly.

Cytotoxicity to leukemia cell and enhancement of immunologic functions of jiexinkang (JXK, traditional Chinese medicine) were observed in 34 cases of leukemia in vitro. The results showed that the leukemia cytotoxicity in the group of vincristine combined with JXK was significantly higher than that in vincristine alone. It was also found among all the observed cases that 20 refractory or recurred patients resistant to vincristine showed an obvious intention of the anti-toxicity efficiency when JXK was added. Jiexinkang alone had anti-leukemia cell effect, too. We explored JXK effects on immunologic functions in mice, and found that IFNr and NK activities of normal and experimental model mice were significantly higher than those of control group(P < 0.01). The results indicate that JXK has an effect of anti-leukemia cell and may improve the cell-immunologic functions.

To explore the effect of p21(WAF1) on the proliferation and the sensitivity to Vp16 of leukemia cell line K562.

Even though phenylacetate (PA) bas been shown to inhibit the growth and induce differentiation in rat C6 glioma cell line, its mechanisms are still poorly understood. This study is aimed to identify which Hox gene is related to glioma and to observe the change in expression on mRNA level as treated by phenylasetate.

To increase myeloid progenitors resistance to chemotherapy and prevent myelosuppression caused by alkylating agents.

To evaluate the feasibility of combined high dose leucovorin plus 5-fluorouracil infusion for head-neck and digestive tract cancers.

To evaluate the response rate and adverse reactions of xeloda, an analogue of 5-fluorouracil, in the treatment of relapsed and metastatic breast cancer.

To evaluate Amifostin's effect on protecting kidney from cisplatinum (DDP) injury and its adverse reactions and safety.

To determine the feasibility of single dose intravesical epirubicin in the prevention of recurrent superficial bladder carcinoma.

To investigate the effects of sulindac metabolites on the proliferation and apoptosis of human umbilical vein endothelial cell line ECV304 in vitro.

Seven new polyoxygenated cyclohexenes, named uvaribonol A-G (1-7) have been isolated from the ethanol extract of the stems of Uvaria boniana Finet. (Annonaceae), and their structures, including the absolute configuration, were determined by spectral and chemical methods. In vitro cytotoxicity test against several human tumor cell lines indicated that all of the new natural compounds are inactive, but some of the derivatives showed obvious activities. Compound 2a is the most active, exhibiting significant cytotoxicities against KB and Bel7402 cells with IC50 < 1 microgram.ml-1, and against HCT-8 cell with IC50 < 0.1 microgram.ml-1.

The Fugu medicated therapeutic prescription (FGMTP) composed of the medicinal herbs with food usage was investigated on the nutrition components and its anti-tumor activity. The results showed that the ratios of thermogenesis of three calorifacient nutrients were protein (12.34%), fat(5.62%) and carbohydrates (82.0%), respectively. The IC50 values of the water extract from this prescription against the 7901 or K562 cell line colony formations were 3.59 g/L and 25.74 mg/L, and the maximal inhibitory rates against both cell line colony formations were 53.2% and 58.9%; respectively. The maximal inhibitory rates against HepA and S180 transplantation tumors were 35.3% and 35.0%, respectively. It is concluded that the FGMTP possessed obvious antitumor effects.