naphthoquinones and Carcinoma--Ehrlich-Tumor

Cancer is a malignancy of worldwide prevalence, and although new therapeutic strategies are under investigation, patients still resort to reductive or palliative chemotherapy. Side effects are a great concern, since treatment can render patients susceptible to infections or secondary cancers. Thus, design of safer chemotherapeutic drugs must consider the risk of immunotoxicity. Pterocarpans are natural isoflavones that possess immunomodulatory and antineoplastic properties. Ubiquitous in nature, quinones are present in chemotherapeutic drugs such as doxorubicin and mitoxantrone. Our group has patented a hybrid molecule, the pterocarpanquinone LQB-118, and demonstrated its antineoplastic effect in vitro. In this report we describe its antineoplastic effect in vivo and assess its toxicity toward the immune system. Treated mice presented no changes in weight of primary and secondary organs of the immune system nor their cellular composition. Immunophenotyping showed that treatment increased CD4(+) thymocytes and proportionally reduced the CD4(+)CD8(+) subpopulation in the thymus. No significant changes were observed in T CD8(+) peripheral lymphocytes nor was the activation of fresh T cells affected after treatment. LQB-118 induced apoptosis in murine tumor cells in vitro, being synergistic with the autophagy promoter rapamycin. Furthermore, treatment significantly reduced ascites or solid Ehrlich and B16F10 melanoma growth in vivo, and ameliorated side effects such as cachexia. Based on its favorable preclinical profile and considering previous results obtained in vitro, this drug emerges as a promising candidate for further development.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Proliferation; Cell Survival; Female; Melanoma, Experimental; Mice, Inbred C57BL; Naphthoquinones; Pterocarpans; Spleen; T-Lymphocytes; Thymus Gland; Tumor Burden

The purpose of the study was to obtain further in vivo data of antitumor effects and mechanisms triggered by juglone and Q7 in combination with ascorbate. The study was done using Ehrlich ascites tumor-bearing mice. Treatments were intraperitoneal every 24 h for 9 days. Control group was treated with excipient. Previous tests selected the doses of juglone and Q7 plus ascorbate (1 and 100 mg/kg, respectively). Samples of ascitic fluid were collected to evaluate carbonyl proteins, GSH and activity of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Hypoxia inducible factor HIF-1α, GLUT1, proteins driving cell cycle (p53, p16 and cyclin A) and apoptosis (poly-ADP-polymerase PARP, Bax and Bcl-xL) were assessed by western blot. Tumor cells were categorized by the phase of cell cycle using flow cytometry and type of cell death using acridine orange/ethidium bromide. A glucose uptake assessment was performed by liquid scintillation using Ehrlich tumor cells cultured with (14)C-deoxyglucose. Treatments caused increased protein carbonylation and activity of antioxidant enzymes and decreased levels of GSH, HIF-1α, GLUT1 and glucose uptake in tumor cells. They also caused increased number of tumor cells in G1, p53 and p16 activation and decreased cyclin A, but only when combined with ascorbate. Apoptosis was induced mostly when treatments were done with ascorbate, causing PARP and Bax cleavage, and increased Bax/Bcl-xL ratio. Juglone and Q7 in combination with ascorbate caused inhibition of tumor progress in vivo by triggering apoptosis and cell cycle arrest associated with oxidative stress, suppression of HIF-1 and uncoupling of glycolytic metabolism.

Topics: Aminophenols; Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Disease Progression; Male; Mice; Mice, Inbred BALB C; Naphthoquinones

The aim of this study was to enhance the understanding of the antitumor mechanism of 1,4-naphthoquinones and ascorbate. Juglone, phenylaminonaphthoquinone-7, and 9 (Q7/Q9) were evaluated for effects on CT-DNA and DNA of cancer cells. Evaluations in MCF-7 cells are DNA damage, ROS levels, viability, and proliferation. Proteins from MCF-7 lysates were immunoblotted for verifying PARP integrity, γH2AX, and pAkt. Antitumor activity was measured in Ehrlich ascites carcinoma-bearing mice. The same markers of molecular toxicity were assessed in vivo. The naphthoquinones intercalate into CT-DNA and caused oxidative cleavage, which is increased in the presence of ascorbate. Treatments caused DNA damage and reduced viability and proliferation of MCF-7 cells. Effects were potentiated by ascorbate. No PARP cleavage was observed. Naphthoquinones, combined with ascorbate, caused phosphorylation of H2AX and inhibited pAkt. ROS were enhanced in MCF-7 cells, particularly by the juglone and Q7 plus ascorbate. Ehrlich carcinoma was inhibited by juglone, Q7, or Q9, but the potentiating effect of ascorbate was reproduced in vivo only in the cases of juglone and Q7, which caused up to 60% inhibition of tumor and the largest extension of survival. Juglone and Q7 plus ascorbate caused enhanced ROS and DNA damage and inhibited pAkt also in Ehrlich carcinoma cells.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Proliferation; Cell Survival; DNA Damage; Histones; Humans; Male; MCF-7 Cells; Mice; Mice, Inbred BALB C; Naphthoquinones; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species

Naphthoquinones interact with biological systems by generating reactive oxygen species (ROS) that can damage cancer cells. The cytotoxicity and the antitumor activity of 3‑acyl‑2‑phenylamino‑1,4‑naphthoquinones (DPB1‑DPB9) were evaluated in the MCF7 human breast cancer cell line and in male Ehrlich tumor‑bearing Balb/c mice. DPB4 was the most cytotoxic derivative against MCF7 cells (EC50 15 µM) and DPB6 was the least cytotoxic one (EC50 56 µM). The 1,4‑naphthoquinone derivatives were able to cause DNA damage and promote DNA fragmentation as shown by the plasmid DNA cleavage assay (FII form). In addition, 1,4‑naphthoquinone derivatives possibly interacted with DNA as intercalating agents, which was demonstrated by the changes caused in the fluorescence of the DNA‑ethidium bromide complexes. Cell death of MCF7 cells induced by 3‑acyl‑2‑phenylamino‑1,4‑naphthoquinones was mostly due to apoptosis. The DNA fragmentation and subsequent apoptosis may be correlated to the redox potential of the 1,4‑naphthoquinone derivatives that, once present in the cell nucleus, led to the increased generation of ROS. Finally, certain 1,4‑naphthoquinone derivatives and particularly DPB4 significantly inhibited the growth of Ehrlich ascites tumors in mice (73%).

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Ehrlich Tumor; DNA; DNA Damage; Humans; Intercalating Agents; Male; MCF-7 Cells; Mice; Mice, Inbred BALB C; Naphthoquinones; Reactive Oxygen Species; Transplantation, Heterologous

The synthesis and tumor-inhibitory activity of a series of aminonaphthoquinone derivatives of diospyrin, which was isolated from Diospyros montana Roxb., are presented here for the first time. An aminoacetate derivative showed the maximum (approximately 93%) increase in life span in vivo against murine Ehrlich ascites carcinoma (EAC) at a dose of 1 mg kg(-1)day(-1) (ip; five doses), and the lowest IC50 (0.06 microM) in vitro. Further, the same analogue also exhibited considerable enhancement in antiproliferative activity when evaluated against human cell lines, viz. malignant skin melanoma and epidermoid laryngeal carcinoma (IC50=0.06 and 0.92 microM, respectively) in comparison to the natural precursor, diospyrin (IC50=0.82 and 3.58 microM, respectively). Moreover, diospyrin and all its derivatives were found to show significantly greater (approximately 17- to 1441-fold) cytotoxicity against the tumor cells as compared to normal human lymphocytes. All these quinonoids generated substantial amounts of reactive oxygen species in EAC cells, more or less commensurate to their respective IC50 values.

Topics: Animals; Antineoplastic Agents; Benzoquinones; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Proliferation; Drug Design; Electrochemistry; Humans; Mice; Naphthoquinones; Neoplasms; Oxidation-Reduction; Reactive Oxygen Species

The effects of Tabebuia avellanedae (TACE), traditionally prescribed in the treatment of cancer, and the naphtoquinone beta-lapachone (beta-lap) on the growth and differentiation of granulocyte and macrophage progenitor cells (CFU-GM) were studied in Ehrlich ascites tumour-bearing mice. Myelosuppression concomitant with increases in spleen CFU-GM and in serum colony-stimulating activity (CSA) were observed in these animals. Treatment with TACE (30-500 mg/kg) and beta-lap (1-5mg/kg) reversed these effects in a dose-dependent manner. The optimal biologically active doses of 120 mg/kg TACE and 1mg/kg beta-lap prolonged life span of tumour-bearing mice, both producing the same rate of extension in the duration of survival. Toxic manifestations were produced by the higher doses of beta-lap in normal and tumour-bearing mice. In spite of similarities between treatments, TACE concentrations used to treat the animals presented no traces of beta-lap, as measured by TLC and HPLC analyses. Our findings suggest that the antitumour effect of TACE and beta-lap, acting synergistically with other factors, such as specific cytokines, may result from enhanced macrophage activation against tumour cells. In addition, it is clear from our results that hematopoietic disorders produced by tumours are an important pathological condition that must be considered in drug development.

Topics: Animals; Antineoplastic Agents, Phytogenic; Bone Marrow Cells; Carcinoma, Ehrlich Tumor; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Colony-Stimulating Factors; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Male; Mice; Mice, Inbred BALB C; Myelopoiesis; Naphthoquinones; Neoplasms, Experimental; Plant Bark; Plant Extracts; Spleen; Stem Cells; Survival Analysis; Tabebuia

Alkyl ethers (D2 and D7) synthesized from diospyrin (D1), a naphthoquinonoid isolated from Diospyros montana Roxb., were evaluated for cytotoxicity and capacity to generate reactive oxygen species (ROS) in tumour cells.. The tumour inhibitory activity of the quinonoids was assessed in vivo against Ehrlich ascites carcinoma (EAC), while cytotoxicity was determined in vitro on EAC and MCF-7 cancer cells by MTT assay. ROS generated by quinonoids in MCF-7 cells was measured fluorimetrically.. The tumour inhibitory activity, cytotoxicity and ROS generation capacity of quinonoids were found to be D7 > D2 > D1.. Alkyl ethers of D1 were more cytotoxic against tumour cells in vitro as well as in vivo.

Topics: Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Ethers; Humans; Lipid Peroxidation; Mice; Naphthoquinones; Reactive Oxygen Species; Xenograft Model Antitumor Assays

Pharmacological studies with an aqueous extract obtained from leaves of Capraria biflora showed potent cytotoxic, analgesic, antimicrobial and anti-inflammatory activities. It has been demonstrated that biflorin possesses an in vitro cytotoxic activity against tumor cells. The in vivo antitumor activity of biflorin was evaluated on two mouse models, sarcoma 180 and Ehrlich carcinoma. Biflorin was active against both tumors with a very similar profile. In addition, biflorin was also able to increase the response elicited by 5-FU in mice inoculated with both tumors. The results showed a decrease in Ki67 staining in tumor cells from treated-animals when compared with non-treated groups, which suggests an inhibition of tumor proliferation rate. Histopathological analysis from kidneys and liver showed that biflorin possessed weak and reversible toxic effects. It was also demonstrated that biflorin acts as an immunoadjuvant agent, rising the production of ovalbumin-specific antibodies and inducing a discreet increase of the white pulp and nest of megakaryocytic in spleen of treated mice, which can be related to its antitumor properties.

Topics: Adjuvants, Immunologic; Animals; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Carcinoma, Ehrlich Tumor; Female; Fluorouracil; Immunohistochemistry; Indicators and Reagents; Ki-67 Antigen; Mice; Naphthoquinones; Neoplasm Transplantation; Ovalbumin; Sarcoma 180; Scrophulariaceae

The cytotoxic activity of amino (3a-e), aza-1-antraquinone (4a-e) lapachol derivatives against Ehrlich carcinoma and human K562 leukemia cells was investigated. Cell viability was determined using MTT assay, after 48 (Ehrlich) or 96 h (K562) of culture, and vincristine (for K562 leukemia) and quercetin (for Ehrlich carcinoma) were used as positive controls. The results showed dose-dependent growth-inhibiting activities and that the amino derivatives were active against the assayed cells, whereas the 4a-e derivatives were not. The allylamine derivative 3a was the most active against Ehrlich carcinoma, with IC50 = 16.94 +/- 1.25 microM, and against K562 leukemia, with IC50 = 14.11 +/- 1.39 microM. The analogous lawsone derivative, 5a, was also active against Ehrlich carcinoma (IC50 = 23.89 +/- 2.3 microM), although the 5d and 5e derivatives showed lower activity. The interaction between 3a-d and calf thymus DNA was investigated by fluorimetric titration and the results showed a hyperchromic effect indicating binding to DNA as presented of ethidium bromide, used as positive control. The inhibitory action on DNA-topoisomerase II-a was also evaluated by a relaxation assay of supercoiled DNA plasmid, and the etoposide (200 microM) was used as positive control. Significant inhibitory activities were observed for 3a-d at 200 microM and a partial inhibitory action was observed for lapachol and methoxylapachol.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antioxidants; Carcinoma, Ehrlich Tumor; Cell Survival; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; K562 Cells; Mice; Naphthoquinones; Quercetin; Topoisomerase II Inhibitors; Vincristine

Diospyrin, a bisnaphthoquinonoid plant product, shows inhibitory activity against murine tumour in vivo and human cancer cell lines in vitro. Efforts have further been made to obtain synthetic derivatives of diospyrin with the objective of improved therapeutic effects. With the goal to reduce the toxicity towards normal cells and enhance the efficacy to tumour cells, diospyrin was encapsulated in liposomal vesicle and its antitumour potential was observed on the growth of Ehrlich ascites tumour in Swiss mice. It was found that the longevity of the tumour-bearing mice was significantly enhanced by treatment with liposomal diospyrin as compared with the free drug. Biochemical assay of liver function enzymes, viz. LDH, AP, GOT and GPT in blood serum of the tumour-bearing mice showed substantial alterations in the activity of these enzymes. These parameters were, however, restored to near normal level when the drug treatment was given encapsulated in a liposome. Histopathological studies on the liver tissues indicated a near normal pathological status in the treated animals despite being challenged by tumour cells. This study on diospyrin has shown, for the first time, an enhancement of its antitumour effect in vivo through liposomal encapsulation.

Topics: Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Ehrlich Tumor; Diospyros; Drug Compounding; Drug Screening Assays, Antitumor; Liposomes; Liver; Liver Function Tests; Male; Mice; Naphthoquinones; Neoplasm Transplantation

Natural shikonin compounds and their derivatives have cytotoxicity and antitumor effects. This study was to explore in vitro and in vivo antitumor effects of SYUNZ-7 [2 or 3, 11-bis(phenylsulfanyl)-6-isohexenylnaphthazarin] and the mechanisms.. In vitro antiproliferation effects of SYUNZ-7 on human lung adenocarcinoma cell line GLC-82, human nasopharyngeal cancer cell line CNE2, human oral cavity cancer cell line KB, human gastric cancer cell line MGC-803 and human hepatocellular cancer cell line HepG2 were tested by MTT assay. In vivo antitumor effect of SYUNZ-7 was tested using ascitic cancer EAC xenograft in mice and CNE2 xenograft in nude mice models. Cell apoptosis and cell cycle distribution were assessed by flow cytometry. The in vivo effect of SYUNZ-7 on angiogenesis was detected by immunohistochemistry.. The 50% inhibitory concentrations (IC(50)) of SYUNZ-7 to GLC-82, CNE2, KB, MGC-803, and HepG2 cells were (2.18+/-0.04) microg/ml, (4.17+/-0.09) microg/ml, (5.41+/-0.10) microg/ml, (6.41+/-0.14) microg/ml, and (9.99+/-0.21) microg/ml, respectively. Under the treatment of 1, 2, 4, and 8 mg/kg of SYUNZ-7, the inhibitory rates of EAC xenografts in mice were (40.5+/-0.14)%, (50.9+/-2.3)%, (61.7+/-1.8)%, and (65.6+/-7.4)%, respectively (P<0.01). Under the treatment of 1, 2, and 4 mg/kg of SYUNZ-7, the inhibitory rates of CNE2 xenografts in nude mice were 24.7%, 38.3%, and 41.2%, respectively (P<0.05). SYUNZ-7 induced apoptosis of CNE2 cells in time- and concentration-dependent manners, and blocked the transition of CNE2 cells from S to G(2)/M phase. SYUNZ-7 also inhibited the angiogenesis of CNE2 xenografts in nude mice in a concentration-dependent manner.. SYUNZ-7 has strong in vivo and in vitro antitumor effects which are related to inducing cell apoptosis, blocking cell cycle, and inhibiting angiogenesis of tumor.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Ehrlich Tumor; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Female; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Structure; Naphthoquinones; Nasopharyngeal Neoplasms; Neoplasm Transplantation; Neovascularization, Pathologic

Plumbagin, a plant-derived bioactive naphthoquinonoid compound, was converted to a hydroquinonoid derivative, which was studied for its tumour-inhibitory and antileishmanial activities for the first time. A similar chemical transformation was undertaken on an analogous dimeric compound, diospyrin, and its bioassay results were compared with those of the plumbagin derivative. Synthesis of the derivative of plumbagin did not result in a marked enhancement of the tumour-inhibitory activity, whereas the improvement was obvious in the case of diospyrin vis à vis its hydroquinonoid analogue. The conversion of diospyrin to the hydroquinonoid compound also led to a substantial increase in the antileishmanial activity, while a similar conversion of plumbagin failed to do so.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antiparasitic Agents; Carcinoma, Ehrlich Tumor; Cell Division; Inhibitory Concentration 50; Leishmania donovani; Male; Mice; Molecular Structure; Naphthoquinones; Phytotherapy; Plant Extracts; Plant Roots; Plumbaginaceae

The effect of plumbagin, a naphthoquinone from the roots of the Indian medicinal plant Plumbago rosea, and Cobalt-60 gamma radiation was studied on Ehrlich ascites carcinoma in vivo, taking cytogenetic damage and cell cycle changes as experimental endpoints. Plumbagin (5 mg/kg body wt, P1) administered intraperitoneally produced a significant increase in the percentage of S-phase as well as G2-M cells with a corresponding decrease in the G1 phase at different post-treatment times. Radiation (7.5 Gy, RT) alone produced the classical G2 block at 1 hr, which persisted with a continuous increase throughout the post-treatment observation period. The combination treatment produced a similar effect as that of RT on G2-M cells, but its effect on the G1 phase was more pronounced than the latter. While P1 treatment produced a small increase in the percentage of labeled S-phase cells, combination treatment significantly reduced the labeled S-phase cells with a corresponding increase in the unlabeled fraction. Drug or radiation alone significantly increased micronuclei induction at various post-treatment times and the combination of the two further enhanced this effect additively. The mechanism of interaction of P1 with radiation in bringing about this effect is not clear.

Topics: Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Ehrlich Tumor; Cell Cycle; Cytogenetics; Female; Male; Mice; Micronucleus Tests; Naphthoquinones; Radiation-Sensitizing Agents

Inclusion complex of plumbagin was prepared with betacyclodextrin employing neutralization method. The toxicity of the drug was reduced and the antitumor efficacy was enhanced on complexation with betacyclodextrin.

Topics: Absorption; Analysis of Variance; Animals; Antineoplastic Agents, Phytogenic; beta-Cyclodextrins; Carcinogens; Carcinoma, Ehrlich Tumor; Cyclodextrins; Dose-Response Relationship, Drug; Drug Carriers; Drug Synergism; Female; Lethal Dose 50; Mice; Mice, Inbred BALB C; Naphthoquinones; Neoplasm Transplantation

Plumbagin niosome were prepared using a lipid layer hydration method, and drug entrapment was measured. The acute toxicity studies were conducted following treatment with free and niosomal plumbagin. The antitumour activity of niosomal plumbagin in a solid tumor (sarcoma-180) and Ehrlich ascites model was evaluated. Niosome-encapsulated plumbagin was less toxic than free drug. The antitumour activity of the drug was also better after encapsulation. The better anticancer activity can be justified with the help of LD50 survival studies and study of tumour volume doubling time.

Topics: Animals; Antineoplastic Agents, Phytogenic; Capsules; Carcinoma, Ehrlich Tumor; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Drug Carriers; Drug Screening Assays, Antitumor; Liposomes; Mice; Mice, Inbred BALB C; Naphthoquinones; Sarcoma 180; Surface-Active Agents

Topics: Adenoma; Adult; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cystadenoma; Female; Humans; Mammary Neoplasms, Experimental; Mice; Mice, Inbred Strains; Naphthoquinones; Neoplasm Transplantation; Ovarian Neoplasms

An antibiotic, identical with naphthomycin, was isolated from a soil Streptomyces. The antibiotic displayed significant therapeutic activity by ip administration against murine tumors: Ehrlich carcinoma and IMC carcinoma implanted ip. The maximum increase of life-span was more than 169% in Ehrlich carcinoma, and 128% in IMC carcinoma. The antibiotic exhibited a potent cytotoxicity against murine leukemic cells: P388, L1210, and L5178Y. IC50 was 0.4-1.3 microgram/ml in culture. The activity of naphthomycin was reversed by SH compounds: 2-mercaptoethanol, dithiothreitol, and glutathione. DNA and RNA syntheses were more markedly inhibited by naphthomycin than protein synthesis in L5178Y cells. Approximately 50% inhibition of nucleic acid syntheses was observed at an antibiotic concentration of 2 micrograms/ml. Naphthomycin blocked alkaline phosphodiesterase obtained from L5178Y cells: IC50 was ca. 7.6 micrograms/ml. The antibiotic neither caused metaphase arrest nor prevented tubulin polymerization. The results suggest that the mechanism of cytotoxicity of naphthomycin is the inhibition of various SH enzymes, particularly those involved in nucleic acid biosynthesis. The mode of action is unique in the ansamycin group of antibiotics.

Topics: Animals; Antibiotics, Antineoplastic; Carcinoma; Carcinoma, Ehrlich Tumor; Cell Survival; Cells, Cultured; Female; Lethal Dose 50; Leukemia, Experimental; Mice; Mitosis; Naphthoquinones; Neoplasms, Experimental; Soil Microbiology; Streptomyces

Topics: Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Ehrlich Tumor; Hemoglobins; Leukocyte Count; Mice; Mice, Inbred A; Naphthoquinones

Topics: Adenine; Animals; Antibiotics, Antineoplastic; Carcinoma, Ehrlich Tumor; Cell Line; Cell Survival; Glyceraldehyde-3-Phosphate Dehydrogenases; Muscles; Naphthoquinones; Rabbits; Sulfhydryl Compounds; Valine

Effects of xanthomegnin and duclauxin on mitochondrial respiration, L1210 culture cells of murine leukemia and Ehrlich ascitic tumor were compared. Both compounds exhibited similarly potent uncoupling effects on the oxidative phosphorylation of mitochondria and cyto-toxicities on the culture cells, but they were not equal in the anti-tumor activity on Ehrlich ascitic tumor. Duclauxin markedly increased the life-span of mice which were i.p. inoculated with Ehrlich ascitic tumor but xanthomegnin did not exhibit such effect as duclauxin.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Carcinoma, Ehrlich Tumor; Cells, Cultured; Chromones; Female; Leukemia, Experimental; Mice; Mice, Inbred ICR; Mitochondria; Naphthoquinones; Oxidative Phosphorylation; Rats; Uncoupling Agents

The six major components of M-92, a new antibiotic complex produced by Micromonospora verruculosa MCRL 0404 showed a similar type of antimicrobial spectrum. Among these components, VA-2 exhibited the most potent antimicrobial activity, particularly significantly against some Gram-positive bacteria and Neisseria. VA-2 and BN-1 also exhibited marked inhibitory effects against L-forms of Staphylococcus aureus 209P and Mycoplasma. The MICs of VA-2, BA-4 and BN-1 were remarkably affected by the pH of the test medium, the inoculum size and the amount of horse serum added in the medium. By intraperitoneal administration, these components showed good protective effects in mice infected intraperitoneally with Staphylococcus aureus Smith. However, the protective effect decreased remarkably by other administration routes. In addition, components such as VA-2 and BN-1 exhibited cytotoxicity against HeLa S-3 cells in vitro and excellent in vivo antitumor activity against Ehrlich carcinoma. VA-2 possessed a high order of acute toxicity to mice [LD50:1.9 mg/kg (i.p.); 1.8 mg/kg (i.v.)], but others were relatively less toxic.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Bacteria; Carcinoma, Ehrlich Tumor; Female; HeLa Cells; Humans; Lethal Dose 50; Male; Mice; Mice, Inbred ICR; Micromonospora; Mycoplasma; Naphthoquinones; Neisseria; Staphylococcal Infections

Topics: Animals; Carcinoma, Ehrlich Tumor; DNA, Neoplasm; Hydroxylamines; Mice; Naphthoquinones

Topics: Animals; Carcinoma, Ehrlich Tumor; Diamines; DNA; Drug Interactions; Escherichia coli; Male; Mice; Naphthoquinones; Protein Biosynthesis; RNA

The synthesis, characterization, and biochemical evaluation of 1-beta-D-ribofuranosylnaphtho[2,3-d]imidazole-4,9-dione (3), 2-beta-D-ribofuranosylnaphtho[2,3-d]pyrazole-4,9-dione (6), and 2-beta-D-ribofuranosylnaphthol[2,3-d]triazole-4,9-dione (9) are reported. These quinone nucleosides and the corresponding quinone heterocycles were tested as inhibitors of purine nucleotide biosynthesis in Ehrlich ascites cells. The nucleosides 3 and 9 and naphtho[2,3-d]imidazole-4,9-dione were effective inhibitors of hypoxanthine phosphoribosyltransferase.

Topics: Animals; Carcinoma, Ehrlich Tumor; Depression, Chemical; Hypoxanthine Phosphoribosyltransferase; In Vitro Techniques; Magnetic Resonance Spectroscopy; Naphthoquinones; Purine Nucleotides; Ribonucleosides

Some 2,3-bis(substituted methyl)naphthazarins and related compounds were synthesized by the Diels-Alder reaction of benzoquinone and 2,3-dimethylbutadiene followed by oxidation and substitution reactions. These compounds were prepared as potential biological alkylating agents. Screening results indicated that 1,4-diacetyl-6,7-dimethyl-4a,5,8,8a-tetrahydronaphthalene and 5,8-bis(benzoyloxy)-2,3-dimethyl-1,4-naphthoquinone possessed borderline activity against leukemia P388 and that naphthazarin diacetate possessed confirmed cytotoxicity against the cell culture of human epidermoid carcinoma of the nasopharynx.

Topics: Animals; Antineoplastic Agents; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Leukemia L1210; Leukemia, Experimental; Mice; Naphthoquinones; Osteosarcoma; Sarcoma 180; Sarcoma, Experimental

Topics: Animals; Antineoplastic Agents; Bacterial Proteins; Carcinoma, Ehrlich Tumor; DNA; Escherichia coli; Hydroxylamines; Leukemia L1210; Mice; Naphthoquinones; Neoplasm Proteins; RNA; Sarcoma 180

Topics: Acetates; Animals; Bromodeoxyuridine; Bromouracil; Carcinoma, Ehrlich Tumor; Cell Membrane; Cosmic Radiation; DNA; Fluorouracil; Iodine; Mice; Naphthoquinones; Pyrimidines; Radiation Effects; Radiation-Sensitizing Agents; Radiotherapy Dosage

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Mice; Naphthoquinones; Sarcoma 180

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cricetinae; Leukocyte Count; Mammary Neoplasms, Experimental; Mice; Naphthoquinones; Neoplasm Transplantation; Neoplasms, Experimental; Sarcoma 180

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Chemical Phenomena; Chemistry; Naphthoquinones

Topics: Animals; Ascites; Carcinoma, Ehrlich Tumor; Cell-Free System; DNA, Neoplasm; Imines; In Vitro Techniques; Mice; Naphthoquinones; Neoplasm Proteins; Peptide Biosynthesis; RNA, Neoplasm; Time Factors

Topics: Animals; Antineoplastic Agents; Bacteria; Carcinoma, Ehrlich Tumor; Chromatography, Paper; Dogs; Imines; Injections, Intraperitoneal; Injections, Intravenous; Male; Mice; Naphthoquinones; Spectrum Analysis; Xanthomonas

Topics: Acetates; Amides; Animals; Anti-Bacterial Agents; Antineoplastic Agents; Ascites; Bacillus megaterium; Bacillus subtilis; Bacteria; Carcinoma, Ehrlich Tumor; Esters; Male; Mice; Naphthoquinones; Proteus; Pseudomonas; Sarcina; Staphylococcus; Triazoles

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Membrane Permeability; Culture Techniques; Ions; Naphthoquinones; Oxygen; Potassium; Radiation Effects; Radiation-Protective Agents; Radiation-Sensitizing Agents; Radiometry; Rats

Topics: Animals; Carcinoma, Ehrlich Tumor; Chromosomes; Mice; Mitosis; Naphthoquinones

Topics: Animals; Carcinoma, Ehrlich Tumor; Carcinoma, Krebs 2; Hot Temperature; Hydrogen Peroxide; In Vitro Techniques; Mice; Naphthoquinones; Oxygen; Partial Pressure; Spectrum Analysis; Sulfites; Trypan Blue; Vitamin K

Topics: Acetates; Animals; Antineoplastic Agents; Azirines; Bacteria; Carcinoma, Ehrlich Tumor; Naphthoquinones; Quinones

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Benzoquinones; Carcinoma, Ehrlich Tumor; Leukocyte Count; Mechlorethamine; Mice; Naphthoquinones; Quinones; Research; Thiotepa; Toxicology