naphthoquinones and Leukemia--Lymphoid

Some pharmacologic properties of nine antitumor agents from higher plants are described. The agents are vincristine, vinblastine the epiodophyllotoxin derivatives VM-26 and VP-16-213, maytansine, bruceantin, thalicarpine, camptothecin, and lapachol. When sufficient information is available, the agents are discussed with regard to their antitumor activity, mechanism of action, pharmacologic disposition, structure-activity relationships, and toxicity.

Topics: Animals; Antineoplastic Agents, Phytogenic; Aporphines; Camptothecin; Carcinoma, Squamous Cell; Chemical Phenomena; Chemistry; Etoposide; Humans; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Maytansine; Melanoma; Naphthoquinones; Nasopharyngeal Neoplasms; Neoplasms; Neoplasms, Experimental; Phenanthrenes; Structure-Activity Relationship; Teniposide; Vinblastine; Vincristine

Leukemia is the most common blood cancer, and its development starts at diverse points, leading to distinct subtypes that respond differently to therapy. This heterogeneity is rarely taken into account in therapies, so it is still essential to look for new specific drugs for leukemia subtypes or even for therapy-resistant cases. Naphthoquinones (NQ) are considered privileged structures in medicinal chemistry due to their plethora of biological activities, including antimicrobial and anticancer effects. Nitrogen-containing heterocycles such as 1,2,3-1H-triazoles have been identified as general scaffolds for generating glycosidase inhibitors. In the present study, the NQ and 1,2,3-1H-triazole cores have been combined to chemically synthesize 18 new 1,2-furanonaphthoquinones tethered to 1,2,3-1H-triazoles (1,2-FNQT). Their cytotoxicities were evaluated against four different leukemia cell lines, including MOLT-4 and CEM (lymphoid cell lines) and K562 and KG1 (myeloid cell lines), as well as normal human peripheral blood mononucleated cells (PBMCs). The new 1,2-FNQT series showed high cytotoxic potential against all leukemia cell lines tested, and some compounds (12o and 12p) showed even better results than the classical therapeutic compounds such as doxorubicin or cisplatin. Others compounds, such as 12b, are promising because of their high selectivity against lymphoblastic leukemia and their low activity against normal hematopoietic cells. The cells of lymphoid origin (MOLT and CEM) were generally more sensitive than the myeloid cell lines to this series of compounds, and most of the compounds that showed the highest cytotoxicity were similarly active against both cell lines.

Topics: Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Furans; Humans; K562 Cells; Leukemia, Lymphoid; Leukemia, Myeloid; Molecular Structure; Naphthoquinones; Structure-Activity Relationship; Triazoles

The synthesis and evaluation of some 2-substituted-1,4-naphthoquinones 2, S-(1,4-naphthoquinon-2-yl)-mercaptoalkanoic acid amides 4, related benzoquinone and naphthoquinone derivatives 6-9 and 2,3-disubstituted 1,4-naphthoquinones 10-11 were carried out. The antifungal, antibacterial, antiviral and anticancer activities were determined by using the standard assay. The results show that compounds 2b and 10a showed in vitro antiviral activity against Influenza-A Virus and Herpes Simplex Virus and possess pronounced antifungal profile whereas 4a showed anticancer activities against Lymphoid Leukaemia P 388.

Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Influenza A virus; Leukemia, Lymphoid; Mice; Microbial Sensitivity Tests; Naphthoquinones; Simplexvirus; Structure-Activity Relationship

Topics: Animals; Antifibrinolytic Agents; Characidae; Leukemia; Leukemia, Lymphoid; Naphthoquinones; Neoplasms; Neoplasms, Experimental; Sodium; Tritium; Vitamin K