Biomedical subjects

B S Li

Publications and source records attributed to B S Li.

6 recordsLinked to original sources

PubMed1992

[Synthesis and antitumor activity of 4-alkylthio-4-deoxy-4'-demethylepipodophyllotxin derivatives].

As a continuing part of our study on the chemistry and antitumor activity of podophyllotoxin, 11 new C-4 S-substituted podophyllotoxin derivatives were synthesised and screened in vitro against L1210 leukemia and KB cells. Thus, 4'-demethylepipodophyllotoxin was reacted with thiols in the presence of BF3. Et2O or trifluroacetic acid to give thioethers. In addition, 4-bromo-4-deoxy-4'-demethylepipodophyllotoxin, when reacted with thiols, also gave rise to corresponding thioether (4-alkylthio-4-deoxy-4'-demethylepipodophyllotoxins). Compounds 10 and 12 have the same activity as etoposide in the inhibition against L1210 leukemia, and compounds 9, 10, 12 and 15 also have comparable activity with etoposide against KB cells.

Animals↗

PubMed1990

Age-dependent decrease in the heat-inducible DNA sequence-specific binding activity in human diploid fibroblasts.

In order to gain a better understanding of the molecular mechanism of the attenuated heat shock response in aging diploid fibroblasts (Liu, A. Y.-C., Lin, Z., Choi, H.-S., Sorhage, F., and Li, B. (1989) J. Biol. Chem. 264, 12037-12045), we examined the regulation of a heat-inducible, heat shock element (HSE) sequence-specific binding protein in IMR-90 diploid fibroblasts. Using gel retardation assay, we showed that the HSE binding activity in extracts of IMR-90 cells was very dependent on heat shock of the cells; that the induction was transient with a maximal increase observed at 1 h of heat shock. Significantly, the level of this heat-inducible HSE-binding activity was age-dependent, being high in young cells and low in old cells. By Scatchard analysis, we determined that this difference in HSE binding in young and old cells was not due to a change in the affinity of the binding, rather the level of the heat-inducible HSE-binding activity was different. The equilibrium dissociation constants (Kd) were estimated to be 30, 25, and 31 pM for cells with population-doubling levels of 22, 35, and 45, respectively; the corresponding Bmax values were 0.087, 0.042, and 0.0059 pmol of 32P-HSE bound per mg of whole cell extract protein. The decreased 32P-HSE-binding activity in the old cells was not a reflection of global alteration of many transcription factors; assay of the DNA binding activity of activating transcription factor showed little difference as a function of age. Experiments of mixing extracts from young and old cells provided evidence of a dominant inhibitor of the HSE-binding activity in old cells. Probing of protein blots with 32P-HSE showed that the subunit molecular weight of the HSE-binding protein was 83,000 in both young and old cells. The pattern of regulation of this HSE-binding protein upon heat shock and cell aging as well as the identity, in DNA sequence specificity and subunit molecular weight, of this protein with that of the human heat shock gene transcription factor suggest that the HSE-binding protein is involved in the transcriptional activation of hsp genes in IMR-90 cells. We concluded that there was an age-associated decrease in the heat shock gene transcription factor DNA-binding activity and that this could account for the attenuated heat shock gene expression in aging diploid cells.

Base Sequence↗

PubMed1989

Heat shock induction of HSP 89 is regulated in cellular aging.

Induction of heat shock proteins (HSPs) was evaluated as a function of age of the IMR-90 human diploid fibroblasts. Heat shock (42 degrees C) markedly increased the synthesis of proteins with apparent molecular weights of 98, 89, 72, 50, 42 and 25 KDa, with HSP 89 and 72 being most prominent. This heat shock induction of HSPs was inversely correlated to the population doubling level (PDL) of the cell cultures used. For example, the synthesis rate of HSP 89 increased from a basal heat shock of young cells (PDL 18); in the old cells (PDL 51), the increase was from 1% to a maximum of 4% at 10-12 hrs after initiation of the heat shock. Western blot analysis showed that HSP 89 constituted approximately 2 and 10% of total cellular proteins in control and heat shocked (42 degrees C, 12-24 hrs) young cells; corresponding values for the old cells were 2 and 4.5%, respectively. Northern blot quantitation of the amount of mRNA hybridizable to cDNA probes of HSP 89 provided evidence that this age-dependent decrease in induction of HSP 89 in IMR-90 cells was attributable to a transcriptional/pre-translational mechanism.

Blotting, Northern↗

PubMed1989

[Synthesis and antimalarial as well as antitumor activities of 2,4-diamino-6-(N-methyl-substituted benzylamino) quinazolines].

Sixteen 2,4-diamino-6-(N-methyl-substituted benzylamino) quinazolines (I) were synthesized by two different methods. 2-Nitro-5-chloro-benzonitrile was treated with the appropriate N-methyl-substituted benzylamines and I was formed after reduction and cyclization. Another method was reductive methylation, i.e., 2,4-diamino-6-substituted benzylaminoquinazolines reacted with formaldehyde and sodium cyanoborohydride at pH 6.3. Suppressive therapeutic tests in mice infected with Plasmodium berghei showed that four (I6,7,10,16) out of these compounds suppressed all the parasites when administered orally at the dose of 5 mg/kg and produced more than 99% suppression at 2.5 mg/kg. Eight compounds (I1,2,4,5,8-10,15) were found to have antitumor effects against Leukemia cells in culture comparable with or superior to those of the positive control methotrexate.

Animals↗

PubMed1989

[Synthesis and antimalarial and antineoplastic activities of some derivatives of 2,4-diamino-5-methyl-6-substituted benzylaminoquinazolines].

This paper reports the synthesis and the antimalarial and anticancer activities of some derivatives of 2,4-diamino-5-methyl-6-substituted benzylaminoquinazolines. These compounds were synthesized by condensation of 5-methyl-2,4,6-triaminoquinazoline with substituted benzyaldehyde to produce Schiff base, followed by reduction, formylation or nitrosation. The suppressive therapeutic effects against Plasmodium berghei in mice showed that the suppressive rate of three compounds (IV 2,5,6)was 100 per cent at the dosage 5 mg/kg. The anticancer activity in vitro showed that II7 and IV3 had the strongest inhibition and their IC50 against L1210 Leukemia cell were 3.910 X 10(-3) micrograms/ml and 6.172 X 10(-3) micrograms/ml.

Aminoquinolines↗

PubMed1989

[Synthesis and antimalarial as well as antitumor activities of 1-methyl-2,4-diamino-6-(N-methyl-substituted benzylamion) quinazolinium iodides].

Fourteen 1-methyl-2,4-diamino-6-(N-methyl-substituted benzylamino) quinazolinium iodides (II) were synthesized by treatment of 2,4-diamino-6-substituted benzylaminoquinazolines with methyl iodide. Three compounds (II4,7,10) were shown to produce 100% suppression on Plasmodium berghei in mice at oral dose of 20 mg/kg and II4 was found to inhibit twice as much as methotrexate on L1210 Leukemia cells in culture.

Animals↗