Carvacrol and rosemary essential oil manifest cytotoxic, DNA-protective and pro-apoptotic effect having no effect on DNA repair.

For several thousand years natural products were successfully used to treat a variety of diseases and to maintain health in humans, but until now it is not fully known what causes these medicinal effects. In our study we assessed the cytotoxic, DNA-protective and pro-apoptotic effect of two frequently occurring natural compounds, carvacrol and rosemary essential oil, on human hepatoma HepG2 cells. In addition we examined the in vitro incision repair activity of liver cell extracts prepared from hepatocytes isolated from Sprague-Dawley (SD) rats fed with water containing carvacrol or rosemary oil. Using conventional and modified single cell gel electrophoresis we proved that incubation of HepG2 cells with selected concentrations of carvacrol and rosemary oil significantly protected cellular DNA against two dangerous oxidative agents, hydrogen peroxide (H(2)O(2)) and 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). It is interesting that despite this DNA protection, the addition of both volatiles to the drinking water of SD rats had no effect on incision repair capacity of hepatocyte extracts. In this paper we also showed that carvacrol and rosemary oil can trigger apoptotic cell death pathways in HepG2 cells, which is probably connected with their cytotoxicity.

PARP-1 inhibitors: a novel genetically specific agents for cancer therapy.

The nuclear poly(ADP-ribose) polymerase-1 (PARP-1) represents an important novel target in cancer therapy. The enzyme is essential for single strand DNA breaks repair via base excision repair pathway. Inhibition of PARP-1 exerts "synthetic lethality" effect towards the tumors with defects in DNA repair by homologous recombination, specifically the tumors with mutations in the breast cancer associated BRCA1 and BRCA2 genes. Recent clinical data confirmed the early in vitro studies and suggest that PARP-1 inhibitors could be used not only as chemosensitizers but as well as single agents to selective kill tumors with defective DNA repair by homologous recombination. Such concept of "synthetic lethality" for tumors which have lost one DNA repair pathway by targeting a second DNA repair pathway, represents groundbreaking therapeutic strategy. The review highlights our current knowledge and ongoing clinical development/trials of PARP-1 inhibitors.

3-(5-Nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline induces ROS-mitochondrial mediated death signaling and activation of p38 MAPK in murine L1210 leukemia cells.

Quinazoline derivatives are multitarget agents with a broad spectrum of biological activity. 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline (NTCHMTQ) is a new synthetically prepared derivative, which in our previous studies showed antiproliferative and apoptosis inducing activities towards murine L1210 leukemia cells. The aim of this study was to provide the insight into the molecular mechanism regulating NTCHMTQ-induced apoptosis in L1210 cells. The activity of caspases 3, 8 and 9, generation of reactive oxygen species (ROS), mitochondrial membrane potential changes, release of cytochrome c, degradation of PARP and activation of c-Jun N-terminal kinase 1/2 (JNK1/2), p38 MAPK and extracellular-regulated kinase 1/2 (ERK1/2) were investigated. NTCHMTQ induced production of ROS, activation of caspases 3 and 9, cytochrome c release, PARP cleavage and activation of p38 MAPK, with no activation of JNK1/2 and ERK1/2. Our resuls clearly demonstrate that NTCHMTQ induces apoptosis of L1210 leukemia cells through ROS-mitochondrial mediated death signaling and activation of p38 MAPK.

Apoptosis induced by 2-acetyl-3-(6-methoxybenzothiazo)-2-yl-amino-acrylonitrile in human leukemia cells involves ROS-mitochondrial mediated death signaling and activation of p38 MAPK.

Benzothiazoles are multitarget agents with broad spectrum of biological activity. 2-Acetyl-3-(6-methoxybenzothiazo)-2-yl-amino-acrylonitrile (AMBAN) is a new synthetically prepared derivative, which in our previous study showed cytotoxic effects towards tumor cells. The aim of the present study was to examine the antiproliferative and apoptosis inducing activities of AMBAN towards human leukemia HL60 and U937 cells. Further, the molecular mechanism involved in AMBAN-induced apoptosis was investigated. Benzothiazole inhibited the growth and induced programmed cell death of HL60 and U937 cells. In addition, AMBAN elevated the level of reactive oxygen species, decreased the mitochondrial membrane potential, activated caspases 9 and 3, induced the cytochrome c release and PARP cleavage and led to intranucleosomal DNA fragmentation. Further, p38 MAPK was associated with the apoptotic activity of AMBAN. It can be concluded that AMBAN-induced apoptosis in HL60 and U937 cells through mitochondrial/caspase 9/caspase 3-dependent pathway.

Antiproliferative activity and apoptosis induced by 6-bromo-2-(morpholin-1-yl)-4-anilinoquinazoline on cells of leukemia lines.

UNLABELLED: Quinazolines are known to be multitarget agents with broad spectrum of biological activity. AIM: To investigate anticancer activity of newly prepared 6-bromo-2-(morpholin-1-yl)-4-anilinoquinazoline (BMAQ) towards L1210, HL-60 and U-937 leukemia cells. MATERIALS AND METHODS: Growth inhibition of BMAQ-treated cells was determined by cell counting using trypan blue staining technique. Apoptosis and cell cycle profile changes were analysed using internucleosomal DNA fragmentation assay, fluorescence microscopy and flow cytometry. Activity of caspase-3 was determined using colorimetric method. RESULTS: Cell proliferation assay showed that BMAQ caused significant decrease of cell number in a dose-dependent manner. BMAQ induced cell death by apoptosis, based on results from DNA fragmentation, fluorescence microscopy and caspase-3 assays. CONCLUSION: Presented results clearly demonstrate that BMAQ is a promising anticancer agent with significant antiproliferative and apoptotic activities towards leukemia cells in vitro.

4-Amino-3-acetylquinoline-induced apoptosis of murine L1210 leukemia cells involves ROS-mitochondrial-mediated death signaling and activation of p38 MAPK.

Quinolines are known to be multitarget agents with a broad spectrum of biological activity. In a previous study, we showed that newly prepared 4-amino-3-acetylquinoline (AAQ) possesses strong anticancer activities. In this study, we investigated whether AAQ has cytotoxicity in murine L1210 leukemia cells. Results from cell proliferation assays showed that AAQ caused significant decrease in cell number in a dose-dependent manner. The cell death induced by AAQ appeared to involve apoptosis, based on evidence from apoptotic DNA fragmentation, flow cytometry, fluorescence microscopy, and Western blot analyses. We found that AAQ-treated cells had activated p38 MAPK and that apoptosis was processed through a reactive oxygen species (ROS)-dependent mitochondrial pathway. In summary, our results suggest that AAQ can induce apoptosis, at least in part, through the activation of the p38 MAPK pathway in L1210 leukemia cells.

Cytotoxicity of hydroxyapatite, fluorapatite and fluor-hydroxyapatite: a comparative in vitro study.

The purpose of this study was to evaluate the cytotoxicity of two formulations of hydroxyapatite (HA), namely fluorapatite (FA) and fluor-hydroxyapatite (FHA). HA is used as carrier material for antibiotics or anticancer drugs during treatment of bone metastasis. Negative control, represented by HA, was included for comparative purposes. Leukemia cells were used as a model cell line, and the effect of eluates of tested biomaterials on cell proliferation/viability and mechanism of antiproliferative activity were assessed. Study design attempted to reveal the toxicity of tested biomaterials with an emphasis to decide if tested biomaterials have promise for further studies in vivo. Results showed that eluates of FA and FHA inhibit the growth of leukemia cells and induce programmed cell death through mitochondrial/caspase-9/caspase-3-dependent pathway. Due to these differences compare to HA, it is concluded that FA and FHA have promise for evaluation of their behaviour in vivo.

[Signal pathways of cell proliferation and death as targets of potential chemotherapeutics]. / Signálne dráhy bunkovej proliferácie a smrti ako ciele potenciálnych chemoterapeutík.

The purpose of this paper is to review current information concerning signal transduction pathways of cell proliferation and cell death applicable in the research of antitumor compounds with a specific effect. Actually, cancer counts among the world gravest diseases. Research of the mechanisms of action of chemotherapeutics helps us to find compounds with high cytotoxic activity to tumor cells and low or no cytotoxicity to normal cells. Many present studies deal with the ability of drugs to hit the proliferation signal pathways or cell death pathways specifically. Various proliferation signal pathways have been identified, e.g. pathways of mitogen-activated proteinkinases. In original studies, cell death was considered to perform in necrotic and apoptotic forms, whereas in contrast to necrosis, apoptosis represented the programmed process. However, other forms of programmed cell death were discovered, the programmed necrosis and autophagic cell death. Similarly, beside the intrinsic, mitochondrial-mediated, and extrinsic, receptor-mediated pathways, new mechanisms of induction of apoptosis were discovered: the endoplasmic reticulum stress pathway in which calcium plays an important role, the lysosomal pathway and the ceramide-induced pathway. Current information concerning transduction of antiproliferative and death stimuli in cells allows to explain the mechanisms of action of known drugs and also brings novel therapeutical targets which can serve in treatment of such diseases as cancer.

In vitro effects of fluor-hydroxyapatite, fluorapatite and hydroxyapatite on colony formation, DNA damage and mutagenicity.

The number of biomaterials used in biomedical applications has rapidly increased in the past two decades. Fluorapatite (FA) is one of the inorganic constituents of bone or teeth used for hard-tissue repairs and replacements. Fluor-hydroxyapatite (FHA) is a new synthetically prepared composite that in its structure contains the same molecular concentration of OH(-) groups and F(-) ions. The aim of this experimental investigation was to evaluate cytotoxic, genotoxic and mutagenic effects of FHA and FA eluates on Chinese hamster V79 cells and to compare them with the effects of hydroxyapatite (HA) eluate. Cytotoxicity of the biomaterials tested was evaluated by use of the cell colony-formation assay and by direct counting of the cells in each colony. Genotoxicity was assessed by single-cell gel electrophoresis (comet assay) and mutagenicity was evaluated by the Hprt gene-mutation assay and in bacterial mutagenicity tests using Salmonella typhimurium TA100. The results show that the highest test concentrations of the biomaterials (100% and 75% eluates) induced very weak inhibition of colony growth (about 10%). On the other hand, the reduction of cell number per colony induced by these concentrations was in the range from 43% to 31%. The comet assay showed that biomaterials induced DNA breaks, which increased with increasing test concentrations in the order HA

Growth inhibition and apoptosis induced by 2-phenoxymethyl-3H-quinazolin-4-one in HL-60 leukemia cells.

AIM: The aim of the study was to investigate anticancer activity of newly synthesized 2-phenoxymethyl-3H-quinazolin-4-one (PMQ). MATERIALS AND METHODS: Anticancer activity of PMQ was studied towards human HL-60 leukemia cells. Antiproliferative activity of PMQ was determined by direct counting of cells using trypan blue staining technique. Apoptosis and cell cycle profile changes were analysed using internucleosomal DNA fragmentation assay and flow cytometry. Activation of caspases and changes in glutathione level were monitored using colorimetric or luminiscent methods. RESULTS: PMQ induced concentration-dependent cytotoxicity in leukemia cells, with IC(50) of 10.8 +/- 0.9 microM. DNA flow cytometry analysis and DNA ladder formation assay indicated that PMQ actively induced apoptosis of cells accompanied by a block of cells in G(2)/M phase and a marked loss of cells in G(0)/G(1) and S phases. Additionally, the activities of caspase-3 and caspase-9 were increased significantly and a markedly increased level of oxidized glutahione was observed. Inhibition of glutahione synthesis using buthionine sulfoximine sensitized leukemia cells to PMQ, confirming the involvement of ROS in PMQ-induced apoptosis. CONCLUSION: The results of this study clearly demonstrate that PMQ is a promising anticancer drug showing cytostatic and apoptotic effects toward HL-60 leukemia cells mainly through mitochondrial/caspase-9 dependent pathway.

New [1,2,4]triazolo[4,3-c]quinazoline enhances cisplatin- and temozolomide-induced growth inhibition and apoptosis in HL-60 cells.

The purpose of this study was to investigate the therapeutic potential of a newly synthesized [1,2,4]triazolo[4,3-c]quinazoline (NTCHMTQ) alone and in combination with two anticancer drugs (cisplatin and temozolomide) against HL-60 leukemia cell line. The IC50 value of NTCHMTQ toward HL-60 cells was 19.7 microM. No apoptosis and cell cycle changes were observed in cells treated with 5 microM NTCHMTQ alone. Combination of non-toxic concentrations of NTCHMTQ (1-5 microM) with cisplatin or temozolomide sensitized HL-60 cells to these two drugs and significantly enhanced their efficacies, that is illustrated by combination indexes, sub-G0 cell fraction, apoptotic DNA fragmentation and caspase-3 activity. The results suggest that combined therapy of non-toxic concentrations of NTCHMTQ with chemotherapeutics may provide synergistic regimen for treatment of leukemia. However, further in vitro and in vivo experimental drug-cell and drug-drug studies are warranted.

[Cytotoxicity screening and mode of action of natural and synthetically prepared compounds usable in tumour chemotherapy]. / Skríning cytotoxicity in vitro a mechanizmus pôsobenia prírodných a synteticky pripravených látok vyuzitel'ných v chemoterapii nádorov.

The paper reviews the current approaches to cytotoxic effect screening and mode of action of natural and synthetic compounds usable in tumour chemotherapy. Oncological diseases belong to the most frequently occurring and the most serious diseases that threaten millions of human lives. A serious complication of anticancer therapy is an inadequate therapeutic answer which is caused by the resistance of the human organism to the employed drugs, chemotherapeutic agents. Therefore the resistance is one of the driving forces which constantly force us to search for new anticancer effective drugs of natural or synthetic origin. Primary screening in vitro, in which by different methods the sensitivity of cancer cells growing in vitro to cytotoxic compounds is monitored, is commonly and routinely used for searching for new potential cytostatics today. The properties of a potential anticancer compound are characterized by different parameters, which include antiproliferative activity, monitoring of structural and functional changes in the cytoplasmic membrane, changes in cell proteins and nucleic acids content, cell metabolism changes, cell cycle changes, induction of apoptosis, enzymatic activity (dihydrofolate reductase, proteinases, proteinkinases, topoisomerases, tymidylatsynthetase), effect on mitochondria, cell cytoskeleton, telomerase activity, etc. By monitoring these parameters, the mode of action of a cytotoxically effective compound can be followed up.

Cytotoxic/antiproliferative effects of new [1,2,4]triazolo[4,3-c] quinazolines in tumor cell lines HeLa and B16.

Quinazolines - 1,3-benzodiazines are biological active compounds, and some of them act as anticancer drugs. We evaluated cytotoxic/antiproliferative activity of new synthetically prepared [1,2,4]triazolo[4,3-c]quinazolines using tumor cell lines HeLa and B16. The in vitro cytotoxic studies of the most active derivative 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin- 4-yl[1,2,4]triazolo[4,3-c]quinazoline (NTCHMTQ) were complemented by cell cycle analysis, and determination of apoptotic DNA fragmentation. Possible direct interaction of NTCHMTQ with calf thymus DNA was tested by the DNA-modified screen-printed electrode. Five quinazoline derivatives tested acted cytotoxically on both tumor cell lines. The melanoma cells B16 were more sensitive to quinazolines treatment than HeLa cells. The most effective derivative was NTCHMTQ which manifested significant in vitro cytotoxic/antiproliferative effect. NTCHMTQ at micromolar concentrations induced morphological changes and necrosis of B16 cells. NTCHMTQ at concentrations tested did not cause changes in cell cycle, did not induce apoptotic cell death in the B16 cells and did not even behave as a typical intercalating agent.

The effect of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline on cell growth, cell cycle, induction of DNA fragmentation, and activity of caspase 3 in murine leukemia L1210 cells and fibroblast NIH-3T3 cells.

Quinazolines are multitarget agents, which have broad spectrum of biological activity, and some of them are now in cancer clinical testing. 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline is a new synthetically prepared derivative, which in our previous study showed cytotoxic effects on cancer cell lines HeLa and B16. Quinazoline, at micromolar concentrations, induced morphological changes and necrosis of B16 cells, and at nanomolar concentrations it produced changes of F-actin cytoskeleton. It did not cause changes in the cell cycle, did not induce apoptotic cell death in B16 cells, did not have a mutagenic effect, and did not even behave as a typical intercalating agent. Little significant reduction of tumor volume in intramuscular transplanted B16 cells was observed. The aim of the present study was to examine the cytotoxic effect of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline on murine leukemia L1210 cells and fibroblast NIH-3T3 cells. Induction of cell morphology and cell cycle changes, induction of apoptosis and caspase 3 activity were studied. Quinazoline acted cytotoxically on both cell lines. The sensitivity of leukemia L1210 cells to the quinazoline was higher than that of fibroblast NIH-3T3. The IC(100) was 12 microM for L1210 cells and 24 microM for NIH-3T3 cells. No effect of quinazoline on the cell cycle profile of L1210 and NIH-3T3 was detected, however, quinazoline induced an increase of the sub-G(0) cell fraction, apoptotic DNA fragmentation, and apoptotic morphological changes at a concentration of 12 microM. This quinazoline concentration induced caspase 3 activity. Our results demonstrated that induction of apoptotic cell death via activation of caspase 3 contributed to the cytotoxic effects of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline in murine leukemia L1210 cells.

Antimicrobial activity of some substituted triazoloquinazolines.

Fifteen substituted 1,2,4-triazolo[4,3-c]quinazolines were tested for antibacterial and antifungal effects. The most effective derivatives had the triazoloquinazoline skeleton substituted with the pharmacologically active chromophores--morpholine, chlorine and nitro group. The broadest antimicrobial activity was found with 5-morpholin-4-yl-3-(5-nitrothien-2-yl)[1,2,4]triazolo[4,3-c]quinazoline in concentration of 10 mg/L for B. subtilis, 50 mg/L for S. aureus and 100 mg/L for C. tropicalis. The highest tested concentration of derivative caused 83% growth inhibition of R. nigricans.

In vitro cytotoxicity of berberine against HeLa and L1210 cancer cell lines.

Previous studies on anti-cancer activity of protoberberine alkaloids against a variety of cancer cell lines were extended to human uterus HeLa nad murine leukemia L1210 cell lines. Cytotoxicity was measured using in vitro techniques and cell morphology changes were examined by light microscopy in both cytostatic and cytocidal concentration ranges. The IC50 was found to be less than 4 microg/ml, a limit put forward by NCI for classification of the compound as a potential anti-cancer drug. The microscopy examination indicated that at cytocidal concentrations the HeLa and L120 cells died apoptotically. The comparative analysis revealed that berberine belongs to the camptothecin family of drugs characterized by the ability to induce DNA topoisomerase poisoning and hence apoptotic cell death. Although the cytotoxic potency of berberine was found to be several orders of magnitude lower compared to camptothecin, its significance may increase in future in view of the lack of unwanted side effects characteristic for camptothecin compounds currently in clinical use for treatment of cancer.

Cytotoxic and genotoxic effects of some substituted tetrazolo[1,5-c]quinazolines.

Nine substituted tetrazolo[1,5-c]quinazolines have been tested for cytotoxic effects and structure activity relationship on the murine cancer cell line B16 and four bacterial strains. The most cytotoxic activity had non-substituted in the aromatic ring or substituted by bromo- or chloro-group, and in the pyrimidine ring of quinazoline skeleton by phenyl or morpholine group, respectively. In the bacterium all tested quinazolines had a lower antibacterial effect than ampicillin. 9-bromo-5-morpholino-tetrazolo[1,5-c]quinazoline (BMTQ) at the highest concentration tested (30.0 micromol/l) had an acute cytostatic effect manifested by the total inhibition of the cell proliferation. Other concentrations caused a cytotoxicity proportional to the concentration used. The IC50 values were found to be less than 4 microg/ml, a limit put forward by the National Cancer Institute (NCI) for classification of the compound as a potential anticancer drug. BMTQ induced mutations in a dose-related manner, starting from 10 microg/plate in strains TA100 and TA102. Lesser but significant increases in revertant colonies were also obtained in strain TA98. The mutagenity was slightly enhanced by metabolic activation.

Induction of cytotoxicity and ssDNA breaks by 9-bromo-5-morpholino-tetrazolo[1,5-c]quinazoline in tumor cells cultured in vitro.

9-Bromo-5-morpholino-tetrazolo[1,5-c]quinazoline (BMTQ) acted cytotoxically on murine leukemia cell line L1210 and human colon carcinoma cells Caco-2. We found the two highest concentrations of BMTQ (149.2 and 74.6 microM) induced an acute cytotoxic effect, however other tested concentrations (<74.6 microM) manifested a concentration/dependent and time/dependent cytotoxic effect. The sensitivity of murine leukemia cells L1210 and human colon carcinoma cells Caco-2 was expressed in the same order. The cytotoxicity of BMTQ was not accompanied by changes of the cell cycle profile. Following the cytotoxicity-related effects of BMTQ we observed the induction of ssDNA breaks after BMTQ treatment. All the concentrations of BMTQ increased the level of ssDNA breaks 1.3-2.9 times (after 2 h of treatment) and 1.6-2.8 times (after 4 h of treatment) in Caco-2 cells compared to the control. No apoptotic DNA fragmentation induced by BMTQ in Caco-2 cells was recorded.

[Cytotoxic and genotoxic activity of certain preservative agents in cosmetics]. / Cytotoxická a genotoxická aktivita vybraných konzervacných látok pre kozmetické prostriedky.

Cytotoxic effects of the preservative compounds for cosmetics JMAC TD, Bronopol, CA 24, and Euxyl K100 were studied. Bronopol demonstrated the highest cytotoxic effect on the proliferation of V79 and VH10 fibroblast cell lines--the IC100 values being 10 mg/l during the whole experiment. The preservatives CA 24 and Euxyl K100 showed 4-times and 5-times smaller cytotoxic activity than Bronopol IC100 = 42 or 50.3 mg/l). The preservative compounds on silver chloride ions JMAC TD manifested the lowest cytotoxicity of the preservatives tested (IC100 = 150 mg/l); 15-times smaller than Bronopol, 3.5-times smaller than CA 24 and 3-times smaller than Euxyl K100. The biocide JMAC TD did not exhibit mutagenic effects on the bacteria Salmonella typhimurium TA 98 and TA 100.

Biological activity of some 4-anilinoquinazolines: cytotoxic, genotoxic and antiprotease effects, induction of necrosis and changes of actin cytoskeleton.

Fourteen substituted 4-anilinoquinazolines have been tested for cytotoxic effect and structure activity relationships. The most active derivatives were substituted by chlorine or bromine group in the aromatic ring, in the pyrimidine ring by morpholine group and in the aniline skeleton by nitro group in position 4 or 2. Derivatives 6-bromo-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline, 6-bromo-2-morpholin-1-yl)-4-anilinoquinazoline, 2-(morpholin-1-yl)-4-(4'-bromoanilino)-quinazoline and 6-chloro-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline inhibited growth of tumor cell lines HeLa, B16 and L1210. Mutagenic data provided by Ames test showed, that the compounds 6-bromo-2-morpholin-1-yl)-4-anilinoquinazoline and 2-(morpholin-1-yl)- 4-(4'-bromoanilino)quinazoline did not exhibit the mutagenic effect, whereas the compounds 6-bromo-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline and 6-chloro-2-(morpholin-1-yl)-4-(4'-nitroanilino) quinazoline increased slightly the number of revertants of the strain TA 98 without metabolic activation. Concentration 26 micromol/L of 6-bromo-2-(morpholin-1-yl)-4-anilinoquinazoline induced necrosis of tumor cells B16. Concentration 5.2 micromol/l induced a significant increase of filamentous actin in the transformed HepG2 cells. Derivatives 6-bromo-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline, 6-bromo-2-morpholin-1-yl)-4-anilinoquinazoline, 2-(morpholin-1-yl)-4-(4'-bromoanilino)quinazoline and 6-chloro-2-(morpholin-1-yl)-4-(4'-nitroanilino)quinazoline exhibited antiprotease effect on plasmine. This results could be relevant for the anticancer properties of these compounds.