naphthoquinones and Carcinoma-256--Walker

beta-lapachone (beta-lap) is a lipophilic o-naphthoquinone isolated from the bark of the lapacho tree. Initial observations proved its capability for inhibiting growth of Yoshida tumor and Walker 256 carcinosarcoma. beta-Lap redox-cycling in the presence of reductants and oxygen yields "reactive oxygen species" (ROS: O2-, OH and H2O2) which cytotoxicity led to assume its role in beta-lap activity in cells. beta-Lap inhibited DNA synthesis in Trypanosoma cruzi as well as topoisomerases I and II, poly(ADP-ribose) polymerase (PARP) in different cells. These enzymes are essential for maintaining DNA structure. beta-Lap inhibited growth of a large variety of tumor cells including epidermoid laringeal cancer, prostate, colon, ovary and breast cancer and also different types of leukemia cells. Advances in knowledge of apoptosis ("programmed cell death") and necrosis provided useful information for understanding the mechanism of beta-lap cytotoxicity. Thiol-dependent proteases (Calpaine), kinases (e.g. c-JUN NH2-terminal kinase), caspases and nucleases are involved in beta-lap cytotoxicity. These enzymes activity, as well as ROS production by beta-lap redox-cycling, would be essential for beta-lap cytotoxicity. Diaphorase and NAD(P)H-quinone reductase, which catalyse beta-lap redox-cycling and ROS production, seem to play an essential role in beta-lap activity. On these grounds, clinical applications of beta-lap have been suggested.

Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Carcinoma 256, Walker; Humans; Naphthoquinones; Neoplasms; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species; Sarcoma, Yoshida; Topoisomerase I Inhibitors

A series of (1,4)-naphthoquinono [3,2-c]-1H-pyrazoles and their (1,4)-naphthohydroquinone derivatives 2-7 were synthesized and evaluated for antifungal, antibacterial, and anticancer activities. The structure-activity relationship of these compounds was studied and the results show that the compound 2b exhibited in vitro antifungal activity against Candida albicans and Cryptococcus neoformans, and also possessed antibacterial profile against Klebsiella pneumoniae and Escherichia coli whereas 1c showed anticancer activity against Walker 256 Carcinosarcoma in rats.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Candida albicans; Carcinoma 256, Walker; Cryptococcus neoformans; Escherichia coli; Klebsiella pneumoniae; Microbial Sensitivity Tests; Naphthoquinones; Pyrazoles; Rats; Structure-Activity Relationship

A series of 1,4-naphthoquinone derivatives were synthesized and tested for antifungal and antitumor activity against a number of fungal disease causative species and Walker 256 carcinoma cell lines. The results show that the compounds 8a,e and 11b possess pronounced antifungal profile where as 7b and f were found to be active against Walker 256 carcinoma cell lines. Moreover 7c and 11a showed inhibitory effect against reverse transcriptase enzyme from Rauscher Murine Leukemia Virus.

Topics: Animals; Antifungal Agents; Antineoplastic Agents; Carcinoma 256, Walker; Drug Design; Drug Evaluation, Preclinical; Microbial Sensitivity Tests; Naphthoquinones

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

Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] and its analogs [2-(3,7-dimethyl-2,6-octadienyl)-3-hydroxy-1,4-naphthoquinone and 2-(3,3-dibromo-2-propenyl)-3-hydroxy-1,4-naphthoquinone] have been described, among almost a hundred synthesized analogs, as active against rat tumor Walker 256 carcinosarcoma. The acetylglucosylation of lapachol results in a compound which extends lapachol activity becoming effective against mouse lymphocytic leukemia P-388. When mice inoculated with 10(6) leukemic cells were treated with the drug during 9 days, their life span increased 80% over the control animals. Identification spectral data (uv, ir, 1H NMR, and MS) of the compound obtained by synthesis are given.

Topics: Animals; Antineoplastic Agents; Carcinoma 256, Walker; Leukemia, Experimental; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Naphthoquinones; Rats

Topics: Adenocarcinoma; Animals; Anthraquinones; Antineoplastic Agents; Carcinoma; Carcinoma 256, Walker; Cell Line; Leukemia L1210; Mouth Neoplasms; Naphthoquinones; Quinones; Sarcoma 180; Structure-Activity Relationship

Topics: Animals; Anthraquinones; Antineoplastic Agents; Azirines; Bridged-Ring Compounds; Carcinoma 256, Walker; Daunorubicin; Drug Evaluation, Preclinical; Heterocyclic Compounds; L-Lactate Dehydrogenase; Leukemia L1210; Mice; Mitomycins; Naphthoquinones; Neoplasms, Experimental; Quinones; Sarcoma 180; Streptonigrin; Structure-Activity Relationship

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Carcinoma 256, Walker; Hydrazones; Leukemia L1210; Naphthoquinones; Neoplasms, Experimental; Rats

Topics: Animals; Carcinoma 256, Walker; Drug Synergism; Mitomycins; Naphthoquinones; Plant Extracts; Plants, Medicinal; Rats; Sulfones; Thiocyanates